ritonavir and Pneumonia--Viral

To date, there has been little agreement on what drug is the "best" drug for treating severe COVID-19 patients. This study aimed to assess the efficacy and safety of different medications available at present for severe COVID-19.. We searched databases for randomized controlled trials (RCTs) published up to February 28, 2022, with no language restrictions, of medications recommended for patients (aged 16 years or older) with severe COVID-19 infection. We extracted data on trials and patient characteristics, and the following primary outcomes: all-cause mortality (ACM), and treatment-emergent adverse events (TEAEs).. We identified 4021 abstracts and of these included 48 RCTs comprising 9147 participants through database searches and other sources. For decrease in ACM, we found that ivermectin/doxycycline, C-IVIG (i.e., a hyperimmune anti-COVID-19 intravenous immunoglobulin), methylprednisolone, interferon-beta/standard-of-care (SOC), interferon-beta-1b, convalescent plasma, remdesivir, lopinavir/ritonavir, immunoglobulin gamma, high dosage sarilumab (HS), auxora, and imatinib were effective when compared with placebo or SOC group. We found that colchicine and interferon-beta/SOC were only associated with the TEAEs of severe COVID-19 patients.. This study suggested that ivermectin/doxycycline, C-IVIG, methylprednisolone, interferon-beta/SOC, interferon-beta-1b, convalescent plasma (CP), remdesivir, lopinavir/ritonavir, immunoglobulin gamma, HS, auxora, and imatinib were efficacious for treating severe COVID-19 patients. We found that most medications were safe in treating severe COVID-19. More large-scale RCTs are still needed to confirm the results of this study.

Topics: Colchicine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; Doxycycline; Humans; Imatinib Mesylate; Immunization, Passive; Immunoglobulins, Intravenous; Interferon beta-1b; Ivermectin; Lopinavir; Methylprednisolone; Network Meta-Analysis; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Ritonavir

In the past few decades, coronaviruses have risen as a global threat to public health. Currently, the outbreak of coronavirus disease-19 (COVID-19) from Wuhan caused a worldwide panic. There are no specific antiviral therapies for COVID-19. However, there are agents that were used during the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) epidemics. We could learn from SARS and MERS. Lopinavir (LPV) is an effective agent that inhibits the protease activity of coronavirus. In this review, we discuss the literature on the efficacy of LPV in vitro and in vivo, especially in patients with SARS and MERS, so that we might clarify the potential for the use of LPV in patients with COVID-19.

Topics: Animals; Antiviral Agents; Betacoronavirus; Cell Line; Clinical Trials as Topic; Coronavirus Infections; COVID-19; Disease Models, Animal; Humans; Lopinavir; Mice; Middle East Respiratory Syndrome Coronavirus; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus; Treatment Outcome

Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV-IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV-IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV-IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.

Topics: Adenosine Monophosphate; Alanine; Animals; Antibodies, Monoclonal; Antiviral Agents; Betacoronavirus; Clinical Trials as Topic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; Drug Combinations; Humans; Immunization, Passive; Interferon-beta; Lopinavir; Mice, Transgenic; Middle East Respiratory Syndrome Coronavirus; Pandemics; Pneumonia, Viral; Ribavirin; Ritonavir; SARS-CoV-2; Severe acute respiratory syndrome-related coronavirus; Spike Glycoprotein, Coronavirus

The new coronavirus pneumonia (NCP), also named as COVID-19 by WHO on Feb 11 2020, is now causing a severe public health emergency in China since. The number of diagnosed cases is more than 40,000 until the submission of this manuscript. Coronavirus has caused several epidemic situations world widely, but the present contagious disease caused by 2019 new coronavirus is unprecedentedly fulminating. The published cohorts of 2019 new coronavirus (n-Cov) are single-center studies, or retrospective studies. We here share the therapeutic experiences of NCP treatment with literature review. Combination of Ribavirin and interferon-α is recommended by the 5(th) edition National Health Commission's Regimen (Revised Edition) because of the effect on Middle East respiratory syndrome (MERS), and the effectiveness of Lopinavir/Ritonavir and Remdisivir needs to be confirmed by randomized controlled trial (RCT), given the situation of no specific antivirus drug on NCP is unavailable. Systemic glucocorticosteroid is recommended as a short term use (1~2 mg·kg(-1)·d(-1), 3~5 d) by the 5(th) edition National Health Commission's Regimen (Revised Edition) yet RCTs are expected to confirm the effectiveness. Inappropriate application of antibiotics should be avoided, especially the combination of broad-spectrum antibiotics, for the NCP is not often complicated with bacterial infection.. 新型冠状病毒肺炎（new coronavirus pneumonia，NCP）正在中国引起严重疫情，截至发稿之日，全国确诊人数已逾4万。冠状病毒已经在全世界范围内引起数次疫情，但此次疫情的来势之迅猛及传染性之强前所未有。我们对引起此次疫情的病原体——2019新型冠状病毒知之甚少，目前在国际上发表的临床研究文章或为单中心研究，或为回顾性分析。我们结合在新冠肺炎一线的救治体会及相关发表的研究成果，给大家分享新冠肺炎的治疗经验。抗病毒药物方面，目前仍无特效药物，利巴韦林和干扰素联合用药由于其治疗中东呼吸综合征（MERS）有效，仍被我国新冠肺炎诊疗方案推荐；洛匹那韦/利托那韦和瑞德西韦的疗效有待随机对照临床试验（randomized controlled trial，RCT）评价；糖皮质激素的短期应用（1~2 mg·kg(-1)·d(-1)，3~5 d）被我国诊疗方案推荐，但仍需RCT进一步证实；本次新冠肺炎合并细菌感染较少，应当避免盲目使用抗菌药物，尤其避免联用广谱抗菌药物。.

Topics: Adenosine; Adenosine Monophosphate; Alanine; Anti-Bacterial Agents; Antiviral Agents; China; Coronavirus Infections; COVID-19; Cytochrome P-450 CYP3A Inhibitors; Drug Therapy, Combination; Humans; Lopinavir; Pneumonia, Viral; Retrospective Studies; Ribonucleotides; Ritonavir

The emerging outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 continues to spread all over the world. Agents or vaccines of proven efficacy to treat or prevent human coronavirus infection are in urgent need and are being investigated vigorously worldwide. This review summarizes the current evidence of potential therapeutic agents, such as lopinavir/ritonavir, remdesivir, favipiravir, chloroquine, hydroxychloroquine, interferon, ribavirin, tocilizumab, and sarilumab. More clinical trials are being conducted for further confirmation of the efficacy and safety of these agents in treating COVID-19.

Topics: Adenosine Monophosphate; Alanine; Betacoronavirus; Clinical Trials as Topic; Coronavirus Infections; COVID-19; Drug Combinations; Humans; Hydroxychloroquine; Interferon-alpha; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID-19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID-19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS-CoV-2. Critically ill patients with COVID-19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID-19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Alanine; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azetidines; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Immunomodulation; Interferon-alpha; Lopinavir; Nelfinavir; Nitro Compounds; Pandemics; Pneumonia, Viral; Purines; Pyrazoles; Ribavirin; Ritonavir; SARS-CoV-2; Sulfonamides; Thiazoles

The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection.. No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19.. The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Alanine; Amides; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antiviral Agents; Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Immunoglobulins; Immunologic Factors; Indoles; Lopinavir; Oseltamivir; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; Ritonavir; SARS-CoV-2; Withholding Treatment

Several antiretroviral drugs are being considered for the treatment of COVID-19, the disease caused by a newly identified coronavirus, (SARS-CoV-2). We systematically reviewed the clinical outcomes of using antiretroviral drugs for the prevention and treatment of coronaviruses and planned clinical trials.. Three databases were screened from inception to 30 March 2020 for studies reporting clinical outcomes of patients with SARS, MERS or COVID-19 treated with antiretrovirals.. From an initial screen of 433 titles, two randomized trials and 24 observational studies provided clinical outcome data on the use of antiretroviral drugs; most studies reported outcomes using LPV/r as treatment. Of the 21 observational studies reporting treatment outcomes, there were three studies among patients with SARS, six studies among patients with MERS and 12 studies among patients with COVID-19. In one randomized trial 99 patients with severe COVID-19 illness were randomized to receive LPV/r (400/100 mg twice a day) and 100 patients to standard of care for 14 days: LPV/r was not associated with a statistically significant difference in time to clinical improvement, although LPV/r given within 12 days of symptoms was associated with shorter time to clinical improvement; 28 day mortality was numerically lower in the LPV/r group (14/99) compared to the control group (25/100), but this difference was not statistically significant. The second trial found no benefit. The certainty of the evidence for the randomized trials was low. In the observational studies 3 out of 361 patients who received LPV/r died; the certainty of evidence was very low. Three studies reported a possible protective effect of LPV/r as post-exposure prophylaxis. Again, the certainty of the evidence was very low due to uncertainty due to limited sample size.. On the basis of the available evidence it is uncertain whether LPV/r and other antiretrovirals improve clinical outcomes or prevent infection among patients at high risk of acquiring COVID-19.

Topics: Adult; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Female; Humans; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus

Currently, there is not any specific effective antiviral treatment for COVID-19. Although most of the COVID-19 patients have mild or moderate courses, up to 5%–10% can have severe, potentially life threatening course, there is an urgent need for effective drugs. Optimized supportive care remains the mainstay of therapy. There have been more than 300 clinical trials going on, various antiviral and immunomodulating agents are in various stages of evaluation for COVID-19 in those trials and some of them will be published in the next couple of months. Despite the urgent need to find an effective antiviral treatment for COVID-19 through randomized controlled studies, certain agents are being used all over the world based on either in-vitro or extrapolated evidence or observational studies. The most frequently used agents both in Turkey and all over the world including chloroquine, hydroxychloroquine, lopinavir/ritonavir, favipiravir and remdesivir will be reviewed here .Nitazoxanide and ivermectin were also included in this review as they have recently been reported to have an activity against SARS-CoV-2 in vitro and are licensed for the treatment of some other human infections.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Humans; Hydroxychloroquine; Ivermectin; Lopinavir; Nitro Compounds; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; SARS-CoV-2; Thiazoles

An outbreak related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019. An extremely high potential for dissemination resulted in the global coronavirus disease 2019 (COVID-19) pandemic in 2020. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale studies. Remdesivir is considered the most promising antiviral agent; it works by inhibiting the activity of RNA-dependent RNA polymerase (RdRp). A large-scale study investigating the clinical efficacy of remdesivir (200 mg on day 1, followed by 100 mg once daily) is on-going. The other excellent anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its efficacy in COVID-19 patients. The protease inhibitor lopinavir/ritonavir (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard care. However, the regimen of LPV/RTV plus ribavirin was shown to be effective against SARS-CoV in vitro. Another promising alternative is hydroxychloroquine (200 mg thrice daily) plus azithromycin (500 mg on day 1, followed by 250 mg once daily on day 2-5), which showed excellent clinical efficacy on Chinese COVID-19 patients and anti-SARS-CoV-2 potency in vitro. The roles of teicoplanin (which inhibits the viral genome exposure in cytoplasm) and monoclonal and polyclonal antibodies in the treatment of SARS-CoV-2 are under investigation. Avoiding the prescription of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, or angiotensin II type I receptor blockers is advised for COVID-19 patients.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Serotherapy; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; RNA-Dependent RNA Polymerase; SARS-CoV-2; Teicoplanin

The ongoing novel coronavirus disease (COVID-19) pandemic is threatening the global human population, including in countries with resource-limited health facilities. Severe bilateral pneumonia is the main feature of severe COVID-19, and adequate ventilatory support is crucial for patient survival. Although our knowledge of the disease is still rapidly increasing, this review summarizes current guidance on the best provision of ventilatory support, with a focus on resource-limited settings. Key messages include that supplemental oxygen is a first essential step for the treatment of severe COVID-19 patients with hypoxemia and should be a primary focus in resource-limited settings where capacity for invasive ventilation is limited. Oxygen delivery can be increased by using a non-rebreathing mask and prone positioning. The presence of only hypoxemia should in general not trigger intubation because hypoxemia is often remarkably well tolerated. Patients with fatigue and at risk for exhaustion, because of respiratory distress, will require invasive ventilation. In these patients, lung protective ventilation is essential. Severe pneumonia in COVID-19 differs in some important aspects from other causes of severe pneumonia or acute respiratory distress syndrome, and limiting the positive end-expiratory pressure level on the ventilator may be important. This ventilation strategy might reduce the currently very high case fatality rate of more than 50% in invasively ventilated COVID-19 patients.

Topics: Adenosine Monophosphate; Alanine; Betacoronavirus; Chloroquine; Continuous Positive Airway Pressure; Coronavirus Infections; COVID-19; Developing Countries; Disease Management; Humans; Hydroxychloroquine; Lopinavir; Lung; Oxygen; Pandemics; Pneumonia, Viral; Respiration, Artificial; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed

To analyze the susceptibility of SARS-CoV-2 in pregnancy and the drugs that can be used to treat pregnancy with COVID-19, so as to provide evidence for drug selection in clinic. By reviewing the existing literature, this paper analyzes the susceptibility of pregnant women to virus, especially to SARS-CoV-2, from the aspects of anatomical, reproductive endocrine and immune changes during pregnancy and screens effective and fetal-safe treatments from the existing drugs. The anatomical structure of the respiratory system is changed during pregnancy, and the virus transmitted by droplets and aerosols is more easily inhaled by pregnant women and is difficult to remove. Furthermore, the prognosis is worse after infection when compared with non-pregnancy women. And changes in reproductive hormones and immune systems during pregnancy collectively make them more susceptible to certain infections. More importantly, angiotensin-converting enzyme (ACE)-2, the SARS-CoV-2 receptor, has been proven highly increased during pregnancy, which may contribute to the susceptibility to SARS-CoV-2. When it comes to treatment, specific drugs for COVID-19 have not been found at present, and taking old drugs for new use in treating COVID-19 has become an emergency method for the pandemic. Particularly, drugs that show superior maternal and fetal safety are worthy of consideration for pregnant women with COVID-19, such as chloroquine, metformin, statins, lobinavir/ritonavir, glycyrrhizic acid, and nanoparticle-mediated drug delivery (NMDD), etc. Pregnant women are susceptible to COVID-19, and special attention should be paid to the selection of drugs that are both effective for maternal diseases and friendly to the fetus. However, there are still many deficiencies in the study of drug safety during pregnancy, and broad-spectrum, effective and fetal-safe drugs for pregnant women need to be developed so as to cope with more infectious diseases in the future.

Topics: Angiotensin-Converting Enzyme 2; Anti-Inflammatory Agents; Antimalarials; Antiviral Agents; Basal Metabolism; Betacoronavirus; Cardiovascular Physiological Phenomena; Chloroquine; Congenital Abnormalities; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Disease Susceptibility; Drug Combinations; Drug Delivery Systems; Female; Functional Residual Capacity; Glycyrrhizic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Interferon Type I; Lopinavir; Metformin; Nanoparticles; Oxygen Consumption; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Pregnancy; Pregnancy Complications, Infectious; Progesterone; Prognosis; Respiratory Physiological Phenomena; Ritonavir; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Stillbirth; Ventilation-Perfusion Ratio

The virus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is currently affecting more than 200 countries and territories worldwide. It has been declared as pandemic by World Health Organization (WHO) and the whole world is suffering from corona virus disease 2019 (COVID-19). Currently, no treatment for SARS-CoV-2 are approved because of lack of evidence, but a number of clinical trials are in process and we are expecting fruitful results very soon. This review focuses on various approaches of treatment and few of the most recent clinical trials carried out in this field.

Topics: Adenosine Monophosphate; Alanine; Amides; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; Darunavir; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Indoles; Interferon-alpha; Interferon-beta; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; SARS-CoV-2

COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health crisis threatening humanity at this point in time. Transmission of the infection occurs by inhalation of infected droplets or direct contact with soiled surfaces and fomites. It should be suspected in all symptomatic children who have undertaken international travel in the last 14 d, all hospitalized children with severe acute respiratory illness, and asymptomatic direct and high-risk contacts of a confirmed case. Clinical symptoms are similar to any acute respiratory viral infection with less pronounced nasal symptoms. Disease seems to be milder in children, but situation appears to be changing. Infants and young children had relatively more severe illness than older children. The case fatality rate is low in children. Diagnosis can be confirmed by Reverse transcriptase - Polymerase chain reaction (RT-PCR) on respiratory specimen (commonly nasopharyngeal and oropharyngeal swab). Rapid progress is being made to develop rapid diagnostic tests, which will help ramp up the capacity to test and also reduce the time to getting test results. Management is mainly supportive care. In severe pneumonia and critically ill children, trial of hydroxychloroquine or lopinavir/ritonavir should be considered. As per current policy, children with mild disease also need to be hospitalized; if this is not feasible, these children may be managed on ambulatory basis with strict home isolation. Pneumonia, severe disease and critical illness require admission and aggressive management for acute lung injury and shock and/or multiorgan dysfunction, if present. An early intubation is preferred over non-invasive ventilation or heated, humidified, high flow nasal cannula oxygen, as these may generate aerosols increasing the risk of infection in health care personnel. To prevent post discharge dissemination of infection, home isolation for 1-2 wk may be advised. As of now, no vaccine or specific chemotherapeutic agents are approved for children.

Topics: Acute Lung Injury; Antiviral Agents; Betacoronavirus; Child; Child, Preschool; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Testing; Disease Outbreaks; Humans; Hydroxychloroquine; Infant; Lopinavir; Palliative Care; Pandemics; Pneumonia, Viral; Protease Inhibitors; Respiratory Distress Syndrome; Reverse Transcriptase Polymerase Chain Reaction; Ritonavir; SARS-CoV-2; Severe Acute Respiratory Syndrome

The full impact of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), on the field of hematopoietic cell transplantation (HCT) is unknown. This perspective paper reviews the following: current COVID-19 epidemiology, diagnosis, and potential therapies; care considerations unique to HCT recipients; and the concept of a learning network to assimilate emerging guidelines and best practices and to optimize patient outcomes through facilitating shared learning and experience across transplantation centers.

Topics: Adenosine Monophosphate; Alanine; Betacoronavirus; Bone Marrow Transplantation; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Serotherapy; COVID-19 Testing; Drug Combinations; Education, Distance; Hematopoietic Stem Cell Transplantation; Humans; Hydroxychloroquine; Immunization, Passive; Infection Control; Information Dissemination; Lopinavir; Pandemics; Pneumonia, Viral; Practice Guidelines as Topic; Real-Time Polymerase Chain Reaction; Ritonavir; SARS-CoV-2; Severity of Illness Index; Tissue Donors

The novel severe acute respiratory syndrome coronavirus 2 is the cause of Coronavirus Disease 2019, a new illness with no effective treatment or vaccine that has reached pandemic proportions. In this document, we analyze how health authorities and agencies around the world position themselves regarding the off-label use of repurposed drugs or new investigational drugs to treat Coronavirus Disease 2019. We review the most promising candidate medicines, including available evidence, clinical recommendations and current options for access. Our concluding remarks stress the importance of administering off-label and investigational drugs in the setting of clinical trials, or at least in standardized scenarios, to generate as much scientific knowledge as achievable while engaging in the best efforts to treat patients and save lives.. O novo severe acute respiratory syndrome coronavírus 2 é a causa da doença por coronavírus 2019, uma doença emergente, sem tratamento eficaz nem vacina, que alcançou proporções de pandemia. Neste documento, analisamos a forma como as autoridades e agências de saúde em todo o Mundo se posicionam em relação ao uso de fármacos off-label ou novos produtos de investigação para o tratamento da doença por coronavírus 2019. Revemos os fármacos mais promissores, incluindo a evidência disponível, as recomendações clínicas e as atuais opções de acesso a estes medicamentos. Concluímos enfatizando a importância de administrar fármacos em uso off-label e produtos de investigação em contexto de ensaios clínicos, ou pelo menos em circunstâncias padronizadas, para que se gere o máximo possível de conhecimento científico a mesmo tempo que se concentram esforços em tratar doentes e salvar vidas.

Topics: Adenosine Monophosphate; Alanine; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Drug Combinations; Drugs, Investigational; Global Health; Humans; Hydroxychloroquine; Lopinavir; Off-Label Use; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Coronavirus disease 2019 (COVID-19) has become a global pandemic. It is still uncontrolled in most countries and no therapies are currently available. Various drugs are under investigation for its treatment. The disease is known to have worse outcomes in patients who have underlying cardiovascular disease. Chloroquine/hydroxychloroquine, azithromycin, remdesivir and lopinavir/ritonavir are currently being studied in trials and show some promise. Conduction disorders, heart failure, and mortality have been reported with the use of these drugs. It is important to have knowledge of potential cardiotoxic effects of these drugs before using them for COVID-19 patients for better allocation of healthcare resources and improvement in clinical outcomes.

Topics: Adenosine Monophosphate; Alanine; Anti-Infective Agents; Azithromycin; Betacoronavirus; Cardiovascular Diseases; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Enzyme Inhibitors; Humans; Hydroxychloroquine; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19.. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes.. In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting.. To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence.

Topics: Amides; Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Evidence-Based Medicine; Humans; Hydroxychloroquine; Indoles; Influenza, Human; Lopinavir; Observational Studies as Topic; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; Ritonavir; SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), initially termed 2019-new CoV (2019-nCoV), is a novel coronavirus responsible for the severe respiratory illness currently ongoing worldwide from the beginning of December 2019. This beta gene virus, very close to bat coronaviruses (bat-CoV-RaTG13) and bat-SL-CoVZC45, causes a severe disease, similar to those caused by Middle East respiratory syndrome (MERS)-CoV and SARS-CoV viruses, featured by low to moderate mortality rate. Unfortunately, the antiviral drugs commonly used in clinical practice to treat viral infections, are not applicable to SARS-Cov-2 and no vaccine is available. Thus, it is extremely necessary to identify new drugs suitable for the treatment of the 2019-nCoV outbreak. Different preclinical studies conducted on other coronaviruses suggested that promising clinical outcomes for 2019-nCoV should be obtained by using alpha-interferon, chloroquine phosphate, arabinol, remdesivir, lopinavir/ritonavir, and anti-inflammatory drugs. Moreover, clinical trials with these suitable drugs should be performed on patients affected by SARS-Cov-2 to prove their efficacy and safety. Finally, a very promising therapeutic drug, tocilizumab, is discussed; it is currently used to treat patients presenting COVID-19 pneumonia. Herein, we recapitulate these experimental studies to highlight the use of antiviral drugs for the treatment of SARS-Cov-2 disease.

Topics: Adenosine Monophosphate; Alanine; Animals; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; COVID-19; Drug Combinations; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Drugs, Investigational; Humans; Indoles; Lopinavir; Multicenter Studies as Topic; Neuraminidase; Pandemics; Pneumonia, Viral; Primates; Ribavirin; Ritonavir; SARS-CoV-2; Treatment Outcome

The fight against the novel coronavirus pneumonia (namely COVID-19) that seriously harms human health is a common task for all mankind. Currently, development of drugs against the novel coronavirus (namely SARS-CoV-2) is quite urgent. Chinese medical workers and scientific researchers have found some drugs to play potential therapeutic effects on COVID-19 at the cellular level or in preliminary clinical trials. However, more fundamental studies and large sample clinical trials need to be done to ensure the efficacy and safety of these drugs. The adoption of these drugs without further testing must be careful. The relevant articles, news, and government reports published on the official and Preprint websites, PubMed and China National Knowledge Infrastructure (CNKI) databases from December 2019 to April 2020 were searched and manually filtered. The general pharmacological characteristics, indications, adverse reactions, general usage, and especially current status of the treatment of COVID-19 of those potentially effective drugs, including chemical drugs, traditional Chinese medicines (TCMs), and biological products in China were summarized in this review to guide reasonable medication and the development of specific drugs for the treatment of COVID-19.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; China; Chloroquine; Coronavirus Infections; COVID-19; Drug Combinations; Drugs, Chinese Herbal; Humans; Indoles; Interferons; Lopinavir; Lung; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; Ritonavir; SARS-CoV-2; Survival Analysis

SARS-CoV-2 is the agent responsible for COVID-19. The infection can be dived into three phases: mild infection, the pulmonary phase and the inflammatory phase. Treatment options for the pulmonary phase include: Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir. The inflammatory phase includes therapeutic options like Tocilizumab, Anakinra, Baricitinib, Eculizumab, Emapalumab and Heparin. Human clinical trials are starting to show some results, in some cases like that of Remdesivir and corticosteroids these are controversial. Coagulopathy is a common complication in severe cases, inflammation and coagulation are intertwined and cross-talking between these two responses is known to happen. A possible amplification of this cross-talking is suggested to be implicated in the severe cases that show both a cytokine storm and coagulopathy.

Topics: Adenosine Monophosphate; Alanine; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neutralizing; Anticoagulants; Antiviral Agents; Azetidines; Betacoronavirus; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Disseminated Intravascular Coagulation; Drug Combinations; Heparin; Humans; Hydroxychloroquine; Inflammation; Interleukin 1 Receptor Antagonist Protein; Lopinavir; Pandemics; Pneumonia, Viral; Purines; Pyrazoles; Ritonavir; SARS-CoV-2; Sulfonamides

The article provides a review of foreign literature for 2020 on existing methods of drug treatment of coronavirus disease COVID-19. To date, in the treatment of COVID-19 in different countries, a little more than 10 drugs are used. The largest number of studies on the testing of these drugs is carried out by scientists from China, the USA, and European countries. It should be noted that among these drugs there is not a single new drug developed specifically for the treatment of COVID-19, the recommended and used drugs have previously been used to treat, as a rule, diseases of the viral etiology, less often another pathology. These suggestions are often based on analogy, the hypothesis of their supposed effectiveness for COVID-19. It can be assumed that a brake on the development of a drug specific for coronavirus disease is a poor knowledge of the pathogenesis of virus invasion in the body's adhesives and the development of complications. The review provides detailed literature data on drugs such as hydroxychloroquine / chloroquine, lopinavir/natinavir, remdesivir, ACE inhibitors and angiotensin converting enzyme receptor blockers, tissue plasminogen activator, as well as plasma transfusion transfusions.. В статье представлен обзор иностранной литературы за 2020 г. по имеющимся методам медикаментозного лечения коронавирусной болезни COVID-19. К настоящему времени при лечении COVID-19 в мире используется чуть больше 10 препаратов, наибольшее число исследований по их апробации проводится учеными Китая, США, стран Европы. Однако нет ни одного нового лекарственного средства, разработанного специально для лечения COVID-19; рекомендуемые и используемые средства ранее применялись для лечения заболеваний вирусной этиологии, реже — другой патологии. Предложения чаще основываются на аналогии, гипотезе о предполагаемой эффективности препаратов и для COVID-19. Можно предположить, что основным фактором, препятствующим разработке специфического для коронавирусной болезни лекарственного средства, является слабое знание патогенеза инвазии вируса в клетки организма и развития осложнений. В обзоре подробно представлены данные литературы о таких препаратах, как гидроксихлорохин/хлорохин, лопинавир/натинавир, ремдесивир, ингибиторы АПФ и блокаторы рецепторов ангиотензинпревращающего фермента, активатор тканевого плазминогена, а также о процедуре переливания плазмы реконвалесцентов.

Topics: Adenosine Monophosphate; Alanine; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tissue Plasminogen Activator

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. Up to now, numerous medicines have been applied or approved for the prevention and control of the virus infection. However, the efficiency of each medicine or combination is completely different or still unknown. In this review, we discuss the types, characteristics, antiviral mechanisms, and shortcomings of recommended candidate medicines for SARS-CoV-2 infection, as well as perspectives of the drugs for the disease treatment, which may provide a theoretical basis for drug screening and application.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; China; Coronavirus Infections; COVID-19; Drug Combinations; Drugs, Chinese Herbal; Humans; Hydroxychloroquine; Indoles; Interferons; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; Ritonavir; SARS-CoV-2; Survival Analysis; Teicoplanin

Topics: Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; HIV Protease Inhibitors; Humans; Length of Stay; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Time Factors; Treatment Outcome; Virus Shedding

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted the repurposing of drugs on the basis of promising

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Administration Schedule; Drug Combinations; Drug Repositioning; Humans; Hydroxychloroquine; Interferons; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Randomized Controlled Trials as Topic; Ribavirin; Ritonavir; SARS-CoV-2; Survival Analysis; Treatment Outcome

SARS-CoV-2 has caused a pandemic which is putting strain on the health-care system and global economy. There is much pressure to develop both preventative and curative therapies for SARS-CoV-2 as there is no evidence to support therapies to improve outcomes in patients with SARS-CoV-2. Medications that inhibit certain steps of virus life cycle that are currently used to treat other illnesses such as Malaria, Ebola, HIV and Hepatitis C are being studied for use against SARS-CoV-2. To date, data is limited for medications that facilitate clinical improvement of COVID-19 infections.

Topics: Adenosine Monophosphate; Alanine; Angiotensin-Converting Enzyme 2; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Disease Progression; Drug Combinations; Drug Repositioning; Esters; Gabexate; Gene Expression Regulation; Guanidines; Host-Pathogen Interactions; Humans; Hydroxychloroquine; Indoles; Lopinavir; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Spike Glycoprotein, Coronavirus

Provide a timely, rigorous, and continuously updated summary of the evidence on the role of lopinavir/ritonavir in the treatment of patients with COVID-19.. We conducted searches in the special L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that performs regular searches in PubMed, Embase, CENTRAL, and other 33 sources. We searched for randomized trials and non-randomized studies evaluating the effect of lopinavir/ritonavir versus placebo or no treatment in patients with COVID-19. Two reviewers independently evaluated potentially eligible studies, according to predefined selection criteria, and extracted data using a predesigned standardized form. We performed meta-analyses using random-effect models and assessed overall certainty in evidence using the GRADE approach. A living, web-based version of this review will be openly available during the COVID-19 pandemic.. Our search strategy yielded 862 references. Finally, we identified 12 studies, including two randomized trials, evaluating lopinavir/ritonavir, in addition to standard care versus standard care alone in 250 adult inpatients with COVID-19. The evidence from randomized trials shows lopinavir/ritonavir may reduce mortality (relative risk: 0.77; 95% confidence interval: 0.45 to 1.3; low certainty evidence), but the anticipated magnitude of the absolute reduction in mortality, varies across different risk groups. Lopinavir/ritonavir also had a slight reduction in the risk of requiring invasive mechanical ventilation, developing respiratory failure, or acute respiratory distress syndrome. However, it did not lead to any difference in the duration of hospitalization and may lead to an increase in the number of total adverse effects. The overall certainty of the evidence was low or very low.. For severe and critical patients with COVID-19, lopinavir/ritonavir might play a role in improving outcomes, but the available evidence is still limited. A substantial number of ongoing studies should provide valuable evidence to inform researchers and decision-makers soon.. Esta revisión sistemática viva tiene como objetivo entregar un resumen oportuno, riguroso y constantemente actualizado de la evidencia disponible sobre los efectos de lopinavir/ritonavir en pacientes con COVID-19.. Se realizó una búsqueda en la plataforma L·OVE COVID-19 (Living OVerview of Evidence), un sistema que mantiene búsquedas regulares en PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) y otras 33 fuentes. Se buscaron ensayos aleatorios y estudios no aleatorios que evaluaran el uso de lopinavir/ritonavir versus placebo o ningún tratamiento en pacientes con COVID-19. Dos revisores evaluaron de forma independiente los artículos potencialmente elegibles, de acuerdo con criterios de selección predefinidos, y extrajeron los datos mediante un formulario estandarizado. Los resultados fueron combinados mediante un metanálisis utilizando modelos de efectos aleatorios y evaluamos la certeza de la evidencia utilizando el método GRADE. Una versión viva de esta revisión estará disponible durante la pandemia de COVID-19.. La búsqueda inicial arrojó 862 referencias. Finalmente, identificamos 12 estudios incluyendo 2 ensayos aleatorios, que evaluaban lopinavir/ritonavir adicionado al tratamiento estándar versus tratamiento estándar en 250 pacientes adultos hospitalizados con COVID-19. Los resultados provenientes de los ensayos aleatorios muestran que el uso de lopinavir/ritonavir puede reducir la mortalidad (riesgo relativo: 0,77; intervalo de confianza 95%: 0,45 a 1,3; certeza de evidencia baja), pero la magnitud de la reducción absoluta de la mortalidad varía según los diferentes grupos de riesgo. El uso de lopinavir/ritonavir mostró además una ligera reducción en el riesgo de requerir ventilación mecánica invasiva, desarrollar insuficiencia respiratoria o síndrome de dificultad respiratoria aguda. No se observó diferencias en la duración de la hospitalización y su uso puede producir un aumento en el número de efectos adversos totales. La certeza global de la evidencia fue baja o muy baja.. Para pacientes graves y críticos con COVID-19, el uso de lopinavir/ritonavir podría desempeñar un papel en la mejora de los resultados, pero la evidencia disponible aún es limitada. La gran cantidad de estudios en curso deberían proporcionar evidencia valiosa para informar a los investigadores y los tomadores de decisiones en el futuro cercano.

Topics: Adult; Antiviral Agents; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Ritonavir; Treatment Outcome

Since a novel coronavirus pneumonia outbreak in late December 2019, coronavirus disease -19 (COVID-19) epidemic has gradually spread worldwide, becoming a major public health event. No specific antivirals are currently available for COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The treatments for COVID-19 are mainly based on the experiences of similar virus such SARS-CoV, MERS-CoV, HIV and influenza viruses. Scientists have taken great efforts to investigate the effective methods for the treatment of COVID-19. Up to now, there are over 1000 clinical studies for COVID-19 all over the world. In this article, we reviewed the current options for COVID-19 therapy including small molecules such as Remdesivir, Favipiravir, Lopinavir/Ritonavir etc, peptide inhibitors of ACE2, Traditional Chinese Medicines and Biologics such as SARS-CoV-2-specific neutralizing antibodies, mesenchymal stem cells and vaccines etc. Meanwhile, we systematically reviewed their clinical safety, clinical applications and progress of antiviral researches. The therapeutic effect of these antiviral drugs is summarized and compared, hoping to provide some ideas for clinical options of COVID-19 treatment and also provide experiences for the life-threatening virus diseases in the future.

Topics: Adenosine Monophosphate; Alanine; Amides; Angiotensin-Converting Enzyme Inhibitors; Antimalarials; Antiviral Agents; Betacoronavirus; Biomedical Research; Coronavirus Infections; COVID-19; COVID-19 Serotherapy; Drug Combinations; Drug Development; Drugs, Chinese Herbal; Humans; Hydroxychloroquine; Immunization, Passive; Indoles; Interferons; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; Ritonavir; SARS-CoV-2

COVID-19 has become a global concern. A large number of reports have explained the clinical characteristics and treatment strategies of COVID-19, but the characteristics and treatment of COVID-19 patient with systemic lupus erythematosus (SLE) are still unclear. Here, we report the clinical features and treatment of the first SLE patient with confirmed COVID-19 pneumonia. This was a 39-year-old woman, diagnosed with SLE 15 years ago, whose overall clinical characteristics (symptoms, laboratory tests, and chest CTs) were similar to those of the general COVID-19 patients. She continued to take the previous SLE drugs (doses of glucocorticoids, hydroxychloroquine, and immunosuppressive agents were not reduced) and was treated with strict antiviral and infection prevention treatment. After the first discharge, she got a recurrence of COVID-19 during her home isolation, and then returned to hospital and continued the previous therapy. Finally, this long-term immune suppressive patient's COVID-19 was successfully cured. The successful recovery of this case has significant reference value for the future treatment of COVID-19 patients with SLE. Key Points • COVID-19 patients with SLE is advocated to continue the medical treatment for SLE. • Hydroxychloroquine may have potential benefits for COVID-19 patients with SLE. • COVID-19 patients with SLE is prone to relapse, and multiple follow-ups are necessary.

Topics: Adult; Anti-Bacterial Agents; Antirheumatic Agents; Antiviral Agents; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Drug Combinations; Female; Glucocorticoids; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lopinavir; Lung; Lupus Erythematosus, Systemic; Moxifloxacin; Mycophenolic Acid; Pandemics; Pneumonia, Viral; Prednisone; Recurrence; Reverse Transcriptase Polymerase Chain Reaction; Ritonavir; RNA, Viral; SARS-CoV-2; Tomography, X-Ray Computed

To compare the effects of treatments for coronavirus disease 2019 (covid-19).. Living systematic review and network meta-analysis.. WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis.. Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.. After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.. 463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty).. Corticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19.. This review was not registered. The protocol is publicly available in the supplementary material.. This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Betacoronavirus; Centers for Disease Control and Prevention, U.S.; China; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Databases, Factual; Drug Combinations; Evidence-Based Medicine; Glucocorticoids; Humans; Hydroxychloroquine; Lopinavir; Network Meta-Analysis; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Respiration, Artificial; Ritonavir; SARS-CoV-2; Severity of Illness Index; Standard of Care; Treatment Outcome; United States

Since the outbreak of novel coronavirus infection pneumonia in Wuhan City, China, in late 2019, such cases have been gradually reported in other parts of China and abroad. Children have become susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of their immature immune function. As the outbreak has progressed, more cases of novel coronavirus infection/pneumonia in children have been reported. Compared with adults, the impact of SARS-CoV-2 infection in children is less severe, with a lower incidence and susceptibility in children, which results in fewer children being tested, thereby underestimating the actual number of infections. Therefore, strengthening the diagnosis of the disease is particularly important for children, and early and clear diagnosis can determine treatment strategies and reduce the harm caused by the disease to children. According to the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (trial version 7) issued by National Health Committee and the latest diagnosis and treatment strategies for novel coronavirus infection pneumonia in children, this review summarizes current strategies on diagnosis and treatment of SARS-CoV-2 infection in children.

Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Asymptomatic Diseases; Betacoronavirus; Biomarkers; Child; Clinical Laboratory Techniques; Coronavirus Infections; Cough; COVID-19; COVID-19 Testing; Drug Combinations; Early Diagnosis; Fever; Humans; Hydroxychloroquine; Interferon-alpha; Lopinavir; Pandemics; Pneumonia, Viral; Practice Guidelines as Topic; Ribavirin; Ritonavir; RNA, Viral; SARS-CoV-2; Severity of Illness Index; Tomography, X-Ray Computed

The unprecedented challenge faced by mankind due to emergence of coronavirus 2019 (COVID-19) pandemic has obligated researchers across the globe to develop effective medicine for prevention and treatment of this deadly infection. The aim of this review is to compile recently published research articles on anti-COVID 19 management with their benefits and risk to facilitate decision making of the practitioners and policy makers. Unfortunately, clinical outcomes reported for antivirals are not consistent. Initial favorable reports on lopinavir/ritonavir contradicted by recent studies. Ostalmovir has conflicting reports. Short term therapy of remdesivir claimed to be beneficial. Favipiravir demonstrated good recovery in some of the cases of COVID-19. Umifenovir (Arbidol) was associated with reduction in mortality in few studies. Overall, until now, U.S. Food and Drug administration issued only emergency use authorization to remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Humans; Indoles; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; SARS-CoV-2

Coronavirus disease 2019, also known as COVID-19, is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2. The infection has now catapulted into a full-blown pandemic across the world, which has affected more than 2 million people and has led to approximately 150,000 fatalities all over the world (WHO). In this review, we elaborate all currently available data that shed light on possible methods for treatment of COVID-19, such as antiviral drugs, corticosteroids, convalescent plasma, and potentially effective vaccines. Additionally, ongoing and discontinued clinical trials that have been carried out for validating probable treatments for COVID-19 are discussed. The review also elaborates the prospective approach and the possible advantages of using convalescent plasma and stem cells for the improvement of clinical symptoms and meeting the demand for an instantaneous cure.

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Alanine; Amides; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Serotherapy; COVID-19 Vaccines; Cytokine Release Syndrome; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Immunologic Factors; Indoles; Interleukin 1 Receptor Antagonist Protein; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; SARS-CoV-2; Severity of Illness Index; Viral Vaccines

Several therapeutic agents have been investigated for treatment of novel coronavirus 2019 (nCOV-2019). We conducted a systematic review and meta-analysis to assess the efficacy of various treatment modalities in nCOV-2019 patients.. A literature search was conducted before 29 June 2020 in PubMed, Google Scholar and Cochrane library databases. A fixed-effect model was applied if I. Fifty studies involving 15 in vitro and 35 clinical studies including 9170 nCOV-2019 patients were included. Lopinavir-ritonavir was significantly associated with shorter mean time to clinical recovery (SMD -0.32; 95% CI -0.57 to -0.06), remdesivir was significantly associated with better overall clinical recovery (RR 1.17; 95% CI 1.07 to 1.29), and tocilizumab was associated with less all-cause mortality (RR 0.38; 95% CI 0.16 to 0.93). Hydroxychloroquine was associated with longer time to clinical recovery and less overall clinical recovery. It additionally had higher all-cause mortality and more total adverse events.. Our meta-analysis suggests that except in vitro studies, no treatment has shown overall favourable outcomes in nCOV-2019 patients. Lopinavir-ritonavir, remdesivir and tocilizumab may have some benefits, while hydroxychloroquine administration may cause harm in nCOV-2019 patients. Results from upcoming large clinical trials may further clarify role of these drugs.

Topics: Adenosine Monophosphate; Alanine; Antibodies, Monoclonal, Humanized; Antiviral Agents; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Europe; Female; Humans; Lopinavir; Male; Pandemics; Pneumonia, Viral; Prognosis; Ritonavir; Survival Analysis; Treatment Outcome

Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is currently no licensed antiviral treatment available to prevent human CoV infection. The widespread clinical use and existing knowledge on antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine in the treatment of previous epidemic diseases, namely, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), may be helpful in the combat with novel SARS-CoV-2 infection. Recent clinical evidence didn't confirm the beneficial role of lopinavir/ritonavir and chloroquine/hydroxychloroquine for COVID-19 patients and their use was reassessed. We provide an overview of the current evidence into the mechanisms of action of these available drugs which are repurposed for treatment of the new virus. Available data identifies remdesivir as an adenosine analogue that can target the RNA-dependent RNA polymerase and block viral RNA synthesis. It has been a promising antiviral drug against a wide array of RNA viruses. 3CLpro is a major CoV protease that cleaves the large replicase polyproteins during viral replication and can be targeted by the protease inhibitor lopinavir/ritonavir but the clinical effects are controversial. Chloroquine/Hydroxychloroquine could impair the replication of SARSCoV-2 by multiple mechanisms and their immunomodulatory properties could ameliorate clinical manifestations that are mediated by immune reactions of the host although its beneficial effects are under question and need to be proven at the clinical level. Existing in vitro and in vivo evidence delineate the molecular mechanisms of these drugs in CoV-infected cells. Numerous studies demonstrated the ability of remdesivir to inhibit SARS-CoV-2 replication but future research would be needed to understand the exact mode of action of lopinavir/ritonavir and chloroquine/hydroxychloroquine in SARS-CoV-2 infected cells and to use this knowledge in the treatment of the current COVID-19.

Topics: Adenosine Monophosphate; Alanine; Animals; Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Humans; Hydroxychloroquine; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Lopinavir/ritonavir has been used for the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) coronavirus infections. It has been suggested that, based on this experience, this drug should also be studied in SARS-CoV2 infection.. We performed a systematic review of the literature regarding the use of lopinavir/ritonavir for the treatment of these three infections. We systematically searched the PubMed database from inception to April 30th, 2020, to identify in-vitro and animal studies and any reports of human use of lopinavir/ritonavir for the treatment of SARS, MERS and COVID-19. We also searched the Clinicatrial.gov to identify ongoing trials.. Five in-vitro studies evaluated the effect of lopinavir/ritonavir in SARS. Three additional in-vitro studies reported the EC50 of the antiviral activity of lopinavir/ritonavir in MERS. We identified no in vitro studies evaluating the effect of lopinavir/ritonavir on the novel coronavirus. Two retrospective matched-cohort studies reported the use of lopinavir/ritonavir in combination with ribavirin for SARS patients. Three case reports and one retrospective study described the use of lopinavir/ritonavir in MERS. Twenty-two papers describe the use of lopinavir/ritonavir in adult patients with COVID-19.. The existing literature does not suffice for assessing whether Lopinavir/ritonavir has any benefit in SARS, MERS or COVID-19.

Topics: Antiviral Agents; Betacoronavirus; Clinical Studies as Topic; Coronavirus Infections; COVID-19; Databases, Factual; Humans; Lopinavir; Middle East Respiratory Syndrome Coronavirus; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Severe Acute Respiratory Syndrome

In December 2019, a novel coronavirus SARS-CoV-2, causing the disease COVID-19, spread from Wuhan throughout China and has infected people over 200 countries. Thus far, more than 3,400,000 cases and 240,000 deaths have occurred worldwide, and the coronavirus pandemic continues to grip the globe. While numbers of cases in China have been steadying, the number of infections outside China is increasing at a worrying pace. We face an urgent need to control the spread of the COVID-19 epidemic, which is currently expanding to a global pandemic. Efforts have focused on testing antiviral drugs and vaccines, but there is currently no treatment specifically approved. Traditional Chinese medicine (TCM) is grounded in empirical observations and the Chinese people use TCM to overcome these sorts of plagues many times in thousands of years of history. Currently, the Chinese National Health Commission recommended a TCM prescription of Qing-Fei-Pai-Du-Tang (QFPDT) in the latest version of the "Diagnosis and Treatment guidelines of COVID-19" which has been reported to provide reliable effects for COVID-19. While doubts about TCM still exist today, this review paper will describe the rationalities that QFPDT is likely to bring a safe and effective treatment of COVID-19.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytokine Release Syndrome; Drug Combinations; Drugs, Chinese Herbal; Humans; Indoles; Janus Kinase Inhibitors; Lopinavir; Medicine, Chinese Traditional; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

There have been significant changes to the management of COVID-19 in recent months, including protocols and guidelines designed to prevent, diagnose, and treat the Novel Coronavirus (COVID-19). Several management options have been suggested and have since gained popularity, though we expect additional modifications to be made, as well as more new cases in the coming months, given a lack of definitive treatment and well-controlled experiments. This review highlights the available and potential treatments, along with the challenges associated with each.. We conducted a comprehensive overview of all peer-reviewed studies, editorial comments, and letters to the editor based on a search in PubMed, Google Scholar, Web of Science, and Scopus. The following terms were used: "COVID-19," "SARS-CoV-2," "drug," "treatment," "medication," and "management." All searches were done between March and May 20, 2020.. There are several potential medications available for COVID-19, such as Interferon α (IFN-α), Teicoplanin, Ribavirin, Galidesivir, Lopinavir/Ritonavir, Chloroquine phosphate, Arbidol, Velpatasvir, Favipiravir, Ledipasvir, Remdesivir, Sofosbuvir, Darunavir, Qingfei Paidu Decoction (QPD), and Imatinib. However, we do not have a definitive and specific treatment yet.. We are expecting to have more cases in the coming weeks/months. Therefore, further research is needed to characterize the disease behavior, to find the absolute drug, and to refine the treatment.

Topics: Adenosine Monophosphate; Alanine; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Humans; Imatinib Mesylate; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

To date the severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), known as COVID-19, is for clinicians the most difficult global therapeutic problem. In this landscape, the management of patients with chronic kidney disease, acute kidney injury or patients undergoing immunosuppressant therapies for kidney transplant or glomerular diseases, represent a clinical challenge for nephrologists, especially in patients with severe acute lung involvement. Therefore in this setting, due to the lack of anti-COVID treatment schedules, tailored management is mandatory to reduce the side effects, as consequence of impaired renal function and drugs interactions. We report the main treatment actually used against SARS-CoV-2, underlining its possible use in the nephropatic patients and the central role of nephrologists to improve the clinical outcome.

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Alanine; Amides; Antibodies, Monoclonal; Cobicistat; Coronavirus Infections; COVID-19; Darunavir; Drug Combinations; Humans; Kidney; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Renal Insufficiency, Chronic; Renal Replacement Therapy; Ritonavir

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diatoms; Diet; Diet, High-Fat; Dietary Exposure; Diffusion Magnetic Resonance Imaging; Diketopiperazines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Disease Progression; Disease-Free Survival; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA-Binding Proteins; DNA, Bacterial; DNA, Viral; Docetaxel; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Down-Regulation; Doxorubicin; Drosophila; Drosophila melanogaster; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Edema; Edible Grain; Education, Graduate; Education, Medical, Graduate; Education, Pharmacy; Ehlers-Danlos Syndrome; Electron Transport Complex III; Electron Transport Complex IV; Electronic Nicotine Delivery Systems; Emergency Service, Hospital; Empathy; Emulsions; Endothelial Cells; Endurance Training; Energy Intake; Enterovirus A, Human; Environment; Environmental Monitoring; Enzyme Assays; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Epoxide Hydrolases; Epoxy Compounds; Erythrocyte Count; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Estrogens; Etanercept; Ethiopia; Ethnicity; Ethylenes; Exanthema; Exercise; Exercise Test; Exercise Tolerance; Extracellular Matrix; Extracorporeal Membrane Oxygenation; Eye Infections, Fungal; False Negative Reactions; Fatty Acids; Fecal Microbiota Transplantation; Feces; Female; Femur Neck; Fermentation; Ferritins; Fetal Development; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fibroblasts; Fibroins; Fish Proteins; Flavanones; Flavonoids; Focus Groups; Follow-Up Studies; Food Handling; Food Supply; Food, Formulated; Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; Heart Failure; Heart Rate; Heart Transplantation; Heart-Assist Devices; HEK293 Cells; Heme; Heme Oxygenase-1; Hemolysis; Hemorrhage; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Hexoses; High-Throughput Nucleotide Sequencing; Hippo Signaling Pathway; Histamine; Histamine Agonists; Histidine; Histone Deacetylase 2; HIV Infections; HIV Reverse Transcriptase; HIV-1; Homebound Persons; Homeodomain Proteins; Homosexuality, Male; Hospice and Palliative Care Nursing; HSP70 Heat-Shock Proteins; Humans; Hyaluronan Receptors; Hydrogen; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemia; Hypoglycemic Agents; Hypoxia; Idiopathic Interstitial Pneumonias; Imaging, Three-Dimensional; Imatinib Mesylate; Immunotherapy; Implementation Science; Incidence; INDEL Mutation; Induced Pluripotent Stem Cells; Industrial Waste; Infant; Infant, Newborn; Inflammation; Inflammation Mediators; Infliximab; Infusions, Intravenous; Inhibitory Concentration 50; Injections; Insecticides; Insulin-Like Growth Factor Binding Protein 5; Insulin-Secreting Cells; Interleukin-1; Interleukin-17; Interleukin-8; Internship and Residency; Intestines; Intracellular Signaling Peptides and Proteins; Ion Transport; Iridaceae; Iridoid Glucosides; Islets of Langerhans Transplantation; Isodon; Isoflurane; Isotopes; Italy; Joint Instability; Ketamine; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Neoplasms; Kinetics; Klebsiella pneumoniae; Knee Joint; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lactate Dehydrogenase 5; Laparoscopy; Laser Therapy; Lasers, Semiconductor; Lasers, Solid-State; Laurates; Lead; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Light; Lipid Peroxidation; Lipopolysaccharides; Liposomes; Liver; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Locomotion; Longitudinal Studies; Lopinavir; Lower Urinary Tract Symptoms; Lubricants; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Lymphoma, Mantle-Cell; Lysosomes; Macrophages; Male; Manganese Compounds; MAP Kinase Kinase 4; Mass Screening; Maternal Health; Medicine, Chinese Traditional; Melanoma, Experimental; Memantine; Membrane Glycoproteins; Membrane Proteins; Mesenchymal Stem Cell Transplantation; Metal Nanoparticles; Metalloendopeptidases; Metalloporphyrins; Methadone; Methane; Methicillin-Resistant Staphylococcus aureus; Mexico; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Nude; Mice, SCID; Mice, Transgenic; Microarray Analysis; Microbial Sensitivity Tests; Microbiota; Micronutrients; MicroRNAs; Microscopy, Confocal; Microsomes, Liver; Middle Aged; Milk; Milk, Human; Minority Groups; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Models, Animal; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Epidemiology; Molecular Structure; Molecular Weight; Multilocus Sequence Typing; Multimodal Imaging; Muscle Strength; Muscle, Skeletal; Muscular Diseases; Mutation; Mycobacterium tuberculosis; Myocardial Stunning; Myristates; NAD(P)H Dehydrogenase (Quinone); Nanocomposites; Nanogels; Nanoparticles; Nanotechnology; Naphthalenes; Nasal Cavity; National Health Programs; Necrosis; Needs Assessment; Neoadjuvant Therapy; Neonicotinoids; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm Transplantation; Neoplasms; Neoplastic Stem Cells; Netherlands; Neuroblastoma; Neuroprotective Agents; Neutrophils; NF-kappa B; NFATC Transcription Factors; Nicotiana; Nicotine; Nitrates; Nitrification; Nitrites; Nitro Compounds; Nitrogen; Nitrogen Dioxide; North Carolina; Nuclear Magnetic Resonance, Biomolecular; Nuclear Proteins; Nucleic Acid Hybridization; Nucleosomes; Nutrients; Obesity; Obesity, Morbid; Oceans and Seas; Oncogene Protein v-akt; Oncogenes; Oocytes; Open Reading Frames; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal; Outpatients; Ovarian Neoplasms; Ovariectomy; Overweight; Oxazines; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxides; Oxidoreductases; Oxygen; Oxygen Inhalation Therapy; Oxygenators, Membrane; Ozone; Paclitaxel; Paenibacillus; Pain Measurement; Palliative Care; Pancreatic Neoplasms; Pandemics; Parasympathetic Nervous System; Particulate Matter; Pasteurization; Patient Preference; Patient Satisfaction; Pediatric Obesity; Permeability; Peroxiredoxins; Peroxynitrous Acid; Pharmaceutical Services; Pharmacists; Pharmacy; Phaseolus; Phenotype; Phoeniceae; Phosphates; Phosphatidylinositol 3-Kinases; Phospholipid Transfer Proteins; Phospholipids; Phosphorus; Phosphorylation; Photoperiod; Photosynthesis; Phylogeny; Physical Endurance; Physicians; Pilot Projects; Piperidines; Pituitary Adenylate Cyclase-Activating Polypeptide; Plant Extracts; Plant Leaves; Plant Proteins; Plant Roots; Plaque, Atherosclerotic; Pneumonia; Pneumonia, Viral; Point-of-Care Testing; Polyethylene Glycols; Polymers; Polysorbates; Pore Forming Cytotoxic Proteins; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postprandial Period; Poverty; Pre-Exposure Prophylaxis; Prediabetic State; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy, High-Risk; Prenatal Exposure Delayed Effects; Pressure; Prevalence; Primary Graft Dysfunction; Primary Health Care; Professional Role; Professionalism; Prognosis; Progression-Free Survival; Prolactin; Promoter Regions, Genetic; Proof of Concept Study; Proportional Hazards Models; Propylene Glycol; Prospective Studies; Prostate; Protein Binding; Protein Biosynthesis; Protein Isoforms; Protein Kinase Inhibitors; Protein Phosphatase 2; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein Transport; Proteoglycans; Proteome; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Proton Pumps; Protons; Protoporphyrins; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Veins; Pyrazoles; Pyridines; Pyrimidines; Qualitative Research; Quinoxalines; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Histamine H3; Receptors, Immunologic; Receptors, Transferrin; Recombinant Proteins; Recurrence; Reference Values; Referral and Consultation; Regional Blood Flow; Registries; Regulon; Renal Insufficiency, Chronic; Reperfusion Injury; Repressor Proteins; Reproducibility of Results; Republic of Korea; Research Design; Resistance Training; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency; Resuscitation; Retinal Dehydrogenase; Retreatment; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Ribosomal Proteins; Ribosomes; Risk Assessment; Risk Factors; Ritonavir; Rivers; RNA Interference; RNA-Seq; RNA, Messenger; RNA, Ribosomal, 16S; RNA, Small Interfering; Rosuvastatin Calcium; Rural Population; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salivary Ducts; Salivary Gland Neoplasms; San Francisco; SARS-CoV-2; Satiation; Satiety Response; Schools; Schools, Pharmacy; Seasons; Seawater; Selection, Genetic; Sequence Analysis, DNA; Serine-Threonine Kinase 3; Sewage; Sheep; Sheep, Domestic; Shock, Hemorrhagic; Signal Transduction; Silver; Silymarin; Single Photon Emission Computed Tomography Computed Tomography; Sirolimus; Sirtuin 1; Skin; Skin Neoplasms; Skin Physiological Phenomena; Sleep Initiation and Maintenance Disorders; Social Class; Social Participation; Social Support; Soil; Soil Microbiology; Solutions; Somatomedins; Soot; Specimen Handling; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Spinal Fractures; Spirometry; Staphylococcus aureus; STAT1 Transcription Factor; STAT3 Transcription Factor; Streptomyces coelicolor; Stress, Psychological; Stroke; Stroke Volume; Structure-Activity Relationship; Students, Medical; Students, Pharmacy; Substance Abuse Treatment Centers; Sulfur Dioxide; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Analysis; Survival Rate; Survivin; Sweden; Swine; Swine, Miniature; Sympathetic Nervous System; T-Lymphocytes, Regulatory; Talaromyces; Tandem Mass Spectrometry; tau Proteins; Telemedicine; Telomerase; Telomere; Telomere Homeostasis; Temperature; Terminally Ill; Th1 Cells; Thiamethoxam; Thiazoles; Thiophenes; Thioredoxin Reductase 1; Thrombosis; Thulium; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Time Factors; Titanium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transcriptome; Transforming Growth Factor beta1; Transistors, Electronic; Translational Research, Biomedical; Transplantation Tolerance; Transplantation, Homologous; Transportation; Treatment Outcome; Tretinoin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Tubulin Modulators; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Twins; Ultrasonic Therapy; Ultrasonography; Ultraviolet Rays; United States; Up-Regulation; Uranium; Urethra; Urinary Bladder; Urodynamics; Uromodulin; Uveitis; Vasoconstrictor Agents; Ventricular Function, Left; Vero Cells; Vesicular Transport Proteins; Viral Nonstructural Proteins; Visual Acuity; Vital Capacity; Vitamin D; Vitamin D Deficiency; Vitamin K 2; Vitamins; Volatilization; Voriconazole; Waiting Lists; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Whole Genome Sequencing; Wine; Wnt Signaling Pathway; Wound Healing; Wounds and Injuries; WW Domains; X-linked Nuclear Protein; X-Ray Diffraction; Xanthines; Xenograft Model Antitumor Assays; YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Topics: Adult; Aged; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Humans; Interferon-alpha; Lopinavir; Middle Aged; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Ribavirin; Ritonavir; SARS-CoV-2

No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.. We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao. A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events.. In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).

Topics: Adult; Aged; Antiviral Agents; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Cytochrome P-450 CYP3A Inhibitors; Drug Therapy, Combination; Female; Hospital Mortality; Humans; Intention to Treat Analysis; Lopinavir; Male; Middle Aged; Pandemics; Patient Acuity; Pneumonia, Viral; Proportional Hazards Models; Reverse Transcriptase Polymerase Chain Reaction; Ritonavir; SARS-CoV-2; Time-to-Treatment; Treatment Failure; Viral Load

Topics: Adult; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Drug Combinations; Humans; Lopinavir; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir-ritonavir, and ribavirin for treating patients with COVID-19.. This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688.. Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3-7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5-11]) than the control group (12 days [8-15]; hazard ratio 4·37 [95% CI 1·86-10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir-ritonavir because of biochemical hepatitis. No patients died during the study.. Early triple antiviral therapy was safe and superior to lopinavir-ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted.. The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.

Topics: Adult; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Therapy, Combination; Female; Hong Kong; Hospitalization; Humans; Interferon beta-1b; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ribavirin; Ritonavir; SARS-CoV-2

We will investigate the effectiveness of Interferon Beta 1a, compared to Interferon Beta 1b and the usual therapeutic regimen in COVID-19 in patients that have tested positive and are moderately to severely ill.. This is a single center, open label, randomized, controlled, parallel group, clinical trial that will be conducted at Loghman Hakim Medical Education Center in conjunction with Shahid Beheshti University of Medical Sciences.. COVID-19 confirmed patients will be randomly assigned to one of three groups, with 20 patients in each. The first group (Arm 1) will receive Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-β 1a (Recigen), the second group (Arm 2) will be administered Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-β 1b (Ziferon), and the control group (Arm 3) will be treated by Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra).. Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first. Secondary outcomes include mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. If any patient dies, we have reached an important secondary outcome. SpO2 Improvement between the last and first day of hospitalization, using pulse-oximetry. Duration of hospitalization from date of randomization until the date of hospital discharge or date of death from any cause, whichever comes first. Incidence of new mechanical ventilation uses from date of randomization until the last day of the study. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving. Statistical analysis will be performed by R version 3.6.1 software. We will use Kaplan-Meier to analyze the time to clinical improvement (compared with a log-rank test). Hazard ratios with 95% confidence intervals will be calculated using the Cox proportional-hazards model in crude and adjusted analysis.. Eligible patients will be randomly assigned in a 1:1:1 ratio to receive either Interferon Beta 1a, Interferon Beta 1b or standard care only. Patients will be randomly allocated to three therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package 'randomizeR' in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases.. The present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement.. Of the 60 patients who underwent randomization, 20 patients were assigned to receive Interferon beta-1a, 20 patients were assigned to receive Interferon beta 1b plus standard care and the rest of patients were assigned to receive the standard care alone.. Protocol version 1.2.1. Recruitment is finished, the start date of recruitment was on 9. This study was registered with National Institutes of Health Clinical trials (www.clinicaltrials.gov; identification number NCT04343768, registered April 8, 2020 and first available online April 13, 2020).. The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Topics: Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Drug Therapy, Combination; Host-Pathogen Interactions; Humans; Hydroxychloroquine; Interferon beta-1a; Interferon beta-1b; Iran; Lopinavir; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2; Severity of Illness Index; Time Factors; Treatment Outcome

Colchicine is a well-known drug, which has been used for years to treat a wide range of rheumatic and inflammatory disorders. It helps break the cycle of inflammation through diverse mechanisms including reducing Intereukin-6, Interleukin-8, Tumour Necrosis Factor-alpha besides controlling oxidative stress pathways which all are important and pathologic components in the clinical course and outcome of patients infected with COVID-19. This study aims to assess the anti-inflammatory effects of colchicine in non-severe hospitalized COVID-19 patients.. Prospective, randomized (1:1 ratio), double blind study with parallel group design.. Hospitalized patients with positive nasopharyngeal swab for COVID-19 infection (RT -PCR) and lung Computed tomography scan involvement compatible with COVID-19 pneumonia. The patients are not severely hypoxic, do not need intubation or invasive oxygenation.. known hypersensitivity to colchicine; known hepatic failure; estimated glomerular filtration rate (eGFR)<30 ml/min/1.73m. Eligible enrolled patients will be randomized into two groups. Group A will receive the antiretroviral Lopinavir/Ritonavir (Kaletra) while group B will receive Lopinavir/Ritonavir (Kaletra) + Colchicine 1.5 mg loading then 0.5 mg twice daily orally. All patients in both groups will receive the same amounts of essential minerals, vitamins as antioxidants, and antibiotics. Patients of both groups will be treated under optimal treatment based on the CDC and WHO guidelines and national consensus proposed in Iran including the same dosages of Lopinavir/Ritonavir, antibiotics, trace elements and antioxidants while only in group-B patients Colchicine will be added on top of this protocol.. Primary: Time for clinical improvement and lung CT score changes 14 days after treatment. Secondary: 14 days after treatment - C-Reactive Protein test x Neutrophil to Lymphocyte Ratio , Interleukin-6, malondialdehyde (MDA) levels reduction - Percentage of patients who require supplemental Oxygen - Mean hospital stay length RANDOMISATION: Patients will be allocated to each group (ratio 1:1) by using an online randomization tool: http://www.graphpad.com/quickcalcs/index.cfm BLINDING (MASKING): This will be a double-blind study in which participants and those assessing the final outcomes will be blinded to group assignment.. Regarding the pandemic crisis and our center capacity to hospitalize confirmed COVID-19 patients, a total of 80 patients was found to be logical to be randomized into two groups of 40- patients.. Recruitment is ongoing. Recruitment began on 20/03/2020 and the date by which the recruitment is anticipated to be completed is 30/05/2020.. ClinicalTrials.gov Identifier: NCT04360980, registered 24/04/2020.. The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Topics: Betacoronavirus; Colchicine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Double-Blind Method; Drug Combinations; Hospitalization; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Prospective Studies; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2

Recently, a new coronavirus spreads rapidly throughout the countries and resulted in a worldwide epidemic. Interferons have direct antiviral and immunomodulatory effects. Antiviral effects may include inhibition of viral replication, protein synthesis, virus maturation, or virus release from infected cells. Previous studies have shown that some coronaviruses are susceptible to interferons. The aim of this study was to evaluate the therapeutic effects of IFN-β-1a administration in COVID-19.. In this prospective non-controlled trial, 20 patients included. They received IFN-β-1a at a dose of 44 µg subcutaneously every other day up to 10 days. All patients received conventional therapy including Hydroxychloroquine, and lopinavir/ritonavir. Demographic data, clinical symptoms, virological clearance, and imaging findings recorded during the study.. The mean age of the patients was 58.55 ± 13.43 years. Fever resolved in all patients during first seven days. Although other symptoms decreased gradually. Virological clearance results showed a significant decrease within 10 days. Imaging studies showed significant recovery after 14-day period in all patients. The mean time of hospitalization was 16.8 ± 3.4 days. There were no deaths or significant adverse drug reactions in the 14-day period.. Our findings support the use of IFN-β-1a in combination with hydroxychloroquine and lopinavir/ritonavir in the management of COVID-19.. IRCT20151227025726N12.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hydroxychloroquine; Injections, Subcutaneous; Interferon beta-1a; Lopinavir; Lung; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prospective Studies; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

The outbreak of COVID-19 (caused by SARS-Cov-2) is very serious, and no effective antiviral treatment has yet been confirmed. The adage "old drug, new trick" in this context may suggest the important therapeutic potential of existing drugs. We found that the lopinavir/ritonavir treatment recommended in the fifth edition of the Treatment Plan of China can only help to improve a minority of throat-swab nucleic-acid results (3/15) in hospitals. Our previous use of chloroquine to treat patients with COVID-19 infection showed an improvement in more throat-swab nucleic-acid results (5/10) than the use of lopinavir/ritonavir.. This is a prospective, open-label, randomized controlled, multicenter clinical study. The study consists of three phases: a screening period, a treatment period of no more than 10 days, and a follow-up period for each participant. Participants with COVID-19 infection who are eligible for selection for the study will be randomly allocated to the trial group or the control group. The control group will be given lopinavir/ritonavir treatment for no more than 10 days. The trial group will be given chloroquine phosphate treatment for no more than 10 days. The primary outcome is the clinical recovery time at no more than 28 days after the completion of therapy and follow-up. The secondary outcomes include the rate of treatment success after the completion of therapy and follow-up, the time of treatment success after no more than 28 days, the rate of serious adverse events during the completion of therapy and follow-up, and the time to return to normal temperature (calculated from the onset of illness) during the completion of therapy and follow-up. Comparisons will be performed using two-sided tests with a statistical significance level of 5%.. This experiment should reveal the efficacy and safety of using chloroquine versus lopinavir/ritonavir for patients with mild/general COVID-19 infection. If the new treatment including chloroquine shows a higher rate of throat-swab SARS-CoV-2 real-time fluorescent reverse transcription polymerase chain reaction (RT-PCR) negativity and is safe, it could be tested as a future COVID-19 treatment.. Chinese Clinical Trial Registry, ID: ChiCTR2000029741 . Registered on 11 February 2020.

Topics: Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Prospective Studies; Ritonavir; SARS-CoV-2

To the best of our knowledge, there is no published study on the use of interferon β-1a (IFN β-1a) in the treatment of severe COVID-19. In this randomized clinical trial, the efficacy and safety of IFN β-1a were evaluated in patients with severe COVID-19. Forty-two patients in the interferon group received IFN β-1a in addition to the national protocol medications (hydroxychloroquine plus lopinavir-ritonavir or atazanavir-ritonavir). Each 44-μg/ml (12 million IU/ml) dose of interferon β-1a was subcutaneously injected three times weekly for two consecutive weeks. The control group consisted of 39 patients who received only the national protocol medications. The primary outcome of the study was time to reach clinical response. Secondary outcomes were duration of hospital stay, length of intensive care unit stay, 28-day mortality, effect of early or late administration of IFN on mortality, adverse effects, and complications during the hospitalization. Between 29 February and 3 April 2020, 92 patients were recruited, and a total of 42 patients in the IFN group and 39 patients in the control group completed the study. As the primary outcome, time to the clinical response was not significantly different between the IFN and the control groups (9.7 ± 5.8 versus 8.3 ± 4.9 days, respectively,

Topics: Adult; Aged; Antiviral Agents; Atazanavir Sulfate; Betacoronavirus; Cardiovascular Diseases; Comorbidity; Coronavirus Infections; COVID-19; Diabetes Mellitus; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Hydroxychloroquine; Intensive Care Units; Interferon beta-1a; Length of Stay; Lopinavir; Male; Middle Aged; Neoplasms; Pandemics; Patient Safety; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Survival Analysis; Treatment Outcome

To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection.. ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management.. Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently.. Participants will be randomised 1:1:1:1 to: Group 1: standard of care; Group 2: lopinavir (400mg) / ritonavir (100mg) twice daily for 10 days in tablet form; Group 3: hydroxychloroquine (800mg) 4x200mg administered 12 hours apart on Day 1, followed by 400mg twice a day for 6 days; Group 4: lopinavir /ritonavir plus hydroxychloroquine.. Proportion of participants alive and not having required intensive respiratory support (invasive or non-invasive ventilation) at 15 days after enrolment. A range of clinical and virological secondary outcomes will also be evaluated.. The randomisation schedule will be generated by an independent statistician. Randomisation will be stratified by site and will be in permuted blocks of variable block size. The randomised sequence allocation will only be accessible to the data management group, and site investigators will have individual participant allocation provided through a web-based trial enrolment platform.. This is an open-label study, with researchers assessing the laboratory outcomes blinded to treatment allocation. No unblinding procedures relating to potential adverse effects are therefore required.. We assumed that 5% of participants receiving standard of care would meet the primary outcome, aimed to evaluate whether interventions could lead to a relative risk of 0.5, assuming no interaction between intervention arms. This corresponds to a required sample size of 610 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total sample size therefore is planned to be 2440.. ASCOT protocol version 3, May 5, 2020. Recruitment opened April 4, 2020 and is ongoing, with planned completion of enrolment July 31, 2021.. Australian New Zealand Clinical Trials Registry ( ACTRN12620000445976 ). Prospectively registered April 6, 2020.. The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Topics: Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Hospitalization; Humans; Hydroxychloroquine; Lopinavir; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2; Standard of Care

Topics: Adult; Aged; Anti-Infective Agents; Azithromycin; Betacoronavirus; C-Reactive Protein; Coronavirus Infections; COVID-19; Disease Progression; Drug Combinations; Female; Heart Rate; Humans; Hydroxychloroquine; Intensive Care Units; Lopinavir; Male; Middle Aged; Pandemics; Patient Safety; Pneumonia, Viral; Prognosis; Respiratory Function Tests; Ritonavir; SARS-CoV-2; Survival Analysis; T-Lymphocytes; Tomography, X-Ray Computed; Treatment Outcome

To find effective and safe treatments for COVID-19, the WHO recommended to systemically evaluate experimental therapeutics in collaborative randomised clinical trials. As COVID-19 was spreading in Europe, the French national institute for Health and Medical Research (Inserm) established a transdisciplinary team to develop a multi-arm randomised controlled trial named DisCoVeRy. The objective of the trial is to evaluate the clinical efficacy and safety of different investigational re-purposed therapeutics relative to Standard of Care (SoC) in patients hospitalised with COVID-19.. DisCoVeRy is a phase III, open-label, adaptive, controlled, multicentre clinical trial in which hospitalised patients with COVID-19 in need of oxygen therapy are randomised between five arms: (1) a control group managed with SoC and four therapeutic arms with re-purposed antiviral agents: (2) remdesivir + SoC, (3) lopinavir/ritonavir + SoC, (4) lopinavir/ritonavir associated with interferon (IFN)-β-1a + SoC and (5) hydroxychloroquine + SoC. The primary endpoint is the clinical status at Day 15 on the 7-point ordinal scale of the WHO Master Protocol (V.3.0, 3 March 2020). This trial involves patients hospitalised in conventional departments or intensive care units both from academic or non-academic hospitals throughout Europe. A sample size of 3100 patients (620 patients per arm) is targeted. This trial has begun on 22 March 2020. Since 5 April 2020, DisCoVeRy has been an add-on trial of the Solidarity consortium of trials conducted by the WHO in Europe and worldwide. On 8 June 2020, 754 patients have been included.. Inserm is the sponsor of DisCoVeRy. Ethical approval has been obtained from the institutional review board on 13 March 2020 (20.03.06.51744) and from the French National Agency for Medicines and Health Products (ANSM) on 9 March 2020. Results will be submitted for publication in peer-reviewed journals.. NCT04315948 Eudra-CT 2020-000936-23.

Topics: Adenosine Monophosphate; Adult; Alanine; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Therapy, Combination; Early Warning Score; Extracorporeal Membrane Oxygenation; Hospital Mortality; Hospitalization; Humans; Hydroxychloroquine; Interferon beta-1a; Length of Stay; Lopinavir; Oxygen Inhalation Therapy; Pandemics; Pneumonia, Viral; Respiration, Artificial; Ritonavir; SARS-CoV-2; Standard of Care; Treatment Outcome

1. To compare the safety and efficacy of Hydroxychloroquine with Ribavirin and standard treatment in patients with non-severe COVID-19 infection 2. To compare the safety and efficacy of standard treatment, Lopinavir-ritonavir with Ribavarin, and Hydroxychloroquine with Ribavirin in patients with severe COVID-19 infection TRIAL DESIGN: The study is an Open label, Parallel arm design, stratified randomised controlled trial. Patients will be categorised as non-severe or severe based on predefined criteria. Those who satisfy all inclusion criteria and no exclusion criteria in the respective categories, will be randomly assigned to one of the three treatment groups in a ratio of 1:1 in the non-severe category and 1:1:1 in the severe category.. The trial will be undertaken in a tertiary care center of the country where both Covid and non-Covid patients are getting treated. All patients who are confirmed positive and admitted will be screened for the eligibility criteria and will be enrolled in the study after a written informed consent. Patients will be categorised as non-severe or severe based on predefined criteria.. 1. Age ≥18 years at time of participation in the study 2. Laboratory (RT-PCR) confirmed infection with SARS-CoV-2 3. Symptomatic (severe or non-severe) Covid-19 disease 4. Willingness of study participant to accept randomization to any assigned treatment arm EXCLUSION CRITERIA: 1. Use of medications that are contraindicated with Lopinavir/Ritonavir, Hydroxychloroquine/Chloroquine, or Ribavirin and that cannot be replaced or stopped 2. Patient already on antiretroviral therapy with Lopinavir-Ritonavir based regimen or on Hydroxychloroquine/Chloroquine or on Ribavirin 3. Any known contraindication to test drugs such as retinopathy and QT prolongation 4. Known allergic reaction or inability to take orally of Lopinavir-ritonavir, Hydroxychloroquine/ Chloroquine, Ribavarin 5. Pregnant or breastfeeding females 6. Receipt of any experimental treatment for 2019-nCoV (off-label, compassionate use, or trial related) within 30 days prior to participation in the present study or want to participate after enrolment INTERVENTION AND COMPARATOR: Two therapeutic interventions for non-severe category and three for severe category as described below NON-SEVERE TREATMENT ARMS (NS-GROUP): Treatment Arm Drug A Standard Treatment (ST. Primary endpoints: (1) Time to Clinical recovery (TTCR) defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, oxygen saturation, and alleviation of cough, sustained for at least 72 hours. (2) Time to SARS-CoV-2 RT-PCR negative in upper respiratory tract specimen, time to laboratory recovery of each organ involvement. Secondary Endpoints: All causes mortality, Frequency of respiratory progression (defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support), time to defervescence (in those with fever at enrolment), frequency of requirement for supplemental oxygen or non-invasive ventilation, frequency of requirement for mechanical ventilation, frequency of serious adverse events as per DAIDS table grade of severity. Outcomes are monitored for 28 days from the time of enrolment into the study OR until the patient is discharged or death whichever is longer.. The randomization will be done using a secured central computer-based randomization using a secure website using a central, computer-based randomisation program in a ratio of 1:1 in the non-severe category and 1:1:1 in the severe category.. This is an open labelled study i.e. Study assigned treatment will be known to the research team, the investigators and participants.. Since it is an exploratory trial as COVID-19 being a new disease, all patients who came under the purview of the inclusion criteria within the study period (5 months duration of the recruitment period of the total 6 months duration of the study i.e. from the month of June, 2020 to October 2020) and who have consented for the study will be included.

Topics: Administration, Oral; Adult; Antimalarials; Antiviral Agents; Betacoronavirus; Clinical Protocols; Combined Modality Therapy; Coronavirus Infections; COVID-19; Cytochrome P-450 CYP3A Inhibitors; Female; Humans; Hydroxychloroquine; India; Informed Consent; Lopinavir; Male; Pandemics; Pneumonia, Viral; Ribavirin; Ritonavir; Safety; SARS-CoV-2; Time Factors; Treatment Outcome

We will investigate the effectiveness of high dose Interferon Beta 1a, compared to low dose Interferon Beta 1a (the base therapeutic regimen) in COVID-19 Confirmed Cases (Either RT-PCR or CT Scan Confirmed) with moderate to severe disease TRIAL DESIGN: This is a single center, open label, randomized, controlled, 2-arm parallel group (1:1 ratio), clinical trial.. The eligibility criteria in this study is: age ≥ 18 years, oxygen saturation (SPO2) ≤ 93% or respiratory rate ≥ 24, at least one of the following manifestation: radiation contactless body temperature ≥37.8, Cough, shortness of breath, nasal congestion/ discharge, myalgia/arthralgia, diarrhea/vomiting, headache or fatigue on admission. The onset of the symptoms should be acute (≤ 14 days). The exclusion criteria include refusal to participate, using drugs with potential interaction with lopinavir/ritonavir or interferon-β 1a, blood ALT/AST levels > 5 times the upper limit of normal on laboratory results, pregnant or lactating women, history of alcohol or drug addiction in the past 5 years, the patients who be intubated less than one hours after admission to hospital. This study will be undertaken at the Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences.. COVID- 19 confirmed patients (using the RT-PCR test or CT scan) will be randomly assigned to one of two groups. The intervention group (Arms1) will be treated with lopinavir / ritonavir (Kaletra) + high dose Interferon-β 1a (Recigen) and the control group will be treated with lopinavir / ritonavir (Kaletra) + low dose Interferon-β 1a (Recigen) (the base therapeutic regimen). Both groups will receive standard care consisting of the necessary oxygen support, non-invasive, or invasive mechanical ventilation.. Primary outcome: Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first.. mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. Improvement of SPO2 during the hospitalization, duration of hospitalization from date of randomization until the date of hospital discharge or death, whichever comes first. The incidence of new mechanical ventilation uses from the date of randomization until the last day of the study and the duration of it will be extracted. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving.. Eligible patients with confirmed SARS-Cov-2 infections will be randomly assigned in a 1:1 ratio to two therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package 'randomizeR' in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases.. The present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement.. Of the 100 patients randomised, 50 patients will be assigned to receive high dose Interferon beta-1a plus lopinavir/ritonavir (Kaletra), 50 patients will be assigned to receive low dose Interferon beta 1a plus lopinavir/ritonavir (Kaletra).. Protocol version 1.2.1. Recruitment is finished, the start date of recruitment was on August 20. This study was registered with National Institutes of Health Clinical trials ( www.clinicaltrials.gov ; identification number NCT04521400, https://clinicaltrials.gov/ct2/show/NCT04521400 , registered August 18, 2020 and first available online August 20, 2020).. The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Topics: Adult; Antiviral Agents; Betacoronavirus; Case-Control Studies; Coronavirus Infections; COVID-19; Dose-Response Relationship, Drug; Drug Combinations; Humans; Interferon beta-1a; Lopinavir; Mortality; Outcome Assessment, Health Care; Pandemics; Patient Discharge; Pneumonia, Viral; Respiration, Artificial; Ritonavir; SARS-CoV-2

We will evaluate the efficacy and safety of favipiravir and interferon beta-1a compared to lopinavir/ritonavir and interferon beta-1a in patients with confirmed COVID-19, who are moderately ill.. This is a phase 3, single-center, randomized, open-label, controlled trial with a parallel-group design carried out at Shahid Mohammadi Hospital, Bandar Abbas, Iran.. All patients with age ≥ 20 years admitted at the Severe Acute Respiratory Syndrome Departments of the Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria.. 1. Confirmed diagnosis of infection with SARS-CoV-2 using polymerase chain reaction and/or antibody tests. 2. Moderate COVID-19 pneumonia (via computed tomography and/or X-ray imaging), requiring hospitalization. 3. Hospitalized ≤ 48 h. 4. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm.. 1. Underlying conditions, including chronic hepatitis, cirrhosis, cholestatic liver diseases, cholecystitis, peptic ulcers, acute and chronic renal failure, and peptic ulcers. 2. Severe and critical COVID-19 pneumonia. 3. History of allergy to favipiravir, lopinavir/ritonavir, and interferon beta-1a. 4. Pregnancy and breastfeeding.. Intervention group: favipiravir (Zhejiang Hisun, China) with interferon beta-1a (CinnaGen, Iran). This group will receive 1600 mg favipiravir twice a day for the first day and 600 mg twice a day for the following 4 days with five doses of 44 mcg interferon beta-1a every other day.. lopinavir/ritonavir (Heterd Company, India) with interferon beta-1a (CinnaGen, Iran). This group will receive 200/50 mg lopinavir/ritonavir twice a day for 7 days with five doses of 44 mcg interferon beta-1a every other day. Other supportive and routine care will be the same in both groups.. The primary outcome of the trial is the viral load of SARS-CoV-2 in the nasopharyngeal samples assessed by RT-PCR after 7 days of randomization as well as clinical improvement of fever and O. Eligible patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). A web-based system will be used to generate random numbers for the allocation sequence. Each number relates to one of the study arms.. This is an open-label trial without blinding and placebo control.. A total of 60 patients will be randomized into two groups (30 patients in the intervention group and 30 patients in the control group).. The trial protocol is version 1.0, 22 July 2020. Recruitment began on 25 July 2020 and is anticipated to be completed by 25 September 2020.. Iranian Registry of Clinical Trials (IRCT) IRCT20200506047323N3 . Registered on 22 July 2020.. The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Topics: Adult; Amides; Antiviral Agents; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Drug Combinations; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Interferons; Iran; Lopinavir; Male; Pandemics; Pneumonia, Viral; Pyrazines; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2; Severity of Illness Index; Treatment Outcome; Viral Load

Lopinavir/ritonavir (LPV/r) has been proposed as repurposed drugs for pre-exposure and postexposure prophylaxis as well as therapy of COVID-19. Coronavirus postexposure prophylaxis (COPEP) trial aims at assessing their efficacy as postexposure ring-prophylaxis among adults exposed to SARS-CoV-2.. COPEP is a two-arm open-label cluster-randomised trial conducted in three cantons of Switzerland. Asymptomatic contacts (≥16 years) of individuals diagnosed with COVID-19 will be randomised (2:1) to either LPV/r (400 mg/100 mg two times per day) for 5 days, or a standard of care arm (no treatment). Asymptomatic individuals may be either SARS-CoV-2 positive or negative. Contacts living in the single household will form a cluster and will be randomised into the same arm. All participants will be followed-up for 21 days and undergo daily monitoring for COVID-19 symptoms. The primary endpoint is 21-day incidence of laboratory-confirmed COVID-19 with ≥1 compatible symptom, analysed in an intention-to-treat (ITT) analysis. The secondary endpoints include the 21-day incidence of COVID-19 as well as SARS-CoV-2 infection in a modified ITT analysis, excluding participants who had a positive SARS-CoV-2 RT-PCR from oropharyngeal swab and/or a positive SARS-CoV-2 IgG serology at baseline. Assuming a 21-day incidence for COVID-19 of 20% among contacts without postexposure chemoprophylaxis, to detect a relative risk reduction of 60% (ie, translating in an absolute reduction from 20% to 8%), with a power of 80%, an alpha of 5%. Accounting for design effect of cluster design of circa 1.1, we plan to enrol 200 participants to the LPV/r arm and 100 to the standard of care arm, 300 participants in total.. Ethics approval has been granted by the Commission Cantonale d'Ethique de la Recherche, Ethikkommission Nordwest- und Zentralschweiz and Comitato Etico Cantonale (ref 2020-00864) and Swissmedic (2020DR3056). Results from this trial will be disseminated via journal articles and presentations at national and international conferences.. Clinicaltrials.gov Registry (NCT04364022); Swiss National Clinical Trial Portal Registry (SNCTP 000003732).. CCER 2020-0864.

Topics: Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Post-Exposure Prophylaxis; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2; Switzerland

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diatoms; Diet; Diet, High-Fat; Dietary Exposure; Diffusion Magnetic Resonance Imaging; Diketopiperazines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Disease Progression; Disease-Free Survival; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA-Binding Proteins; DNA, Bacterial; DNA, Viral; Docetaxel; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Down-Regulation; Doxorubicin; Drosophila; Drosophila melanogaster; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Edema; Edible Grain; Education, Graduate; Education, Medical, Graduate; Education, Pharmacy; Ehlers-Danlos Syndrome; Electron Transport Complex III; Electron Transport Complex IV; Electronic Nicotine Delivery Systems; Emergency Service, Hospital; Empathy; Emulsions; Endothelial Cells; Endurance Training; Energy Intake; Enterovirus A, Human; Environment; Environmental Monitoring; Enzyme Assays; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Epoxide Hydrolases; Epoxy Compounds; Erythrocyte Count; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Estrogens; Etanercept; Ethiopia; Ethnicity; Ethylenes; Exanthema; Exercise; Exercise Test; Exercise Tolerance; Extracellular Matrix; Extracorporeal Membrane Oxygenation; Eye Infections, Fungal; False Negative Reactions; Fatty Acids; Fecal Microbiota Transplantation; Feces; Female; Femur Neck; Fermentation; Ferritins; Fetal Development; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fibroblasts; Fibroins; Fish Proteins; Flavanones; Flavonoids; Focus Groups; Follow-Up Studies; Food Handling; Food Supply; Food, Formulated; Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; Heart Failure; Heart Rate; Heart Transplantation; Heart-Assist Devices; HEK293 Cells; Heme; Heme Oxygenase-1; Hemolysis; Hemorrhage; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Hexoses; High-Throughput Nucleotide Sequencing; Hippo Signaling Pathway; Histamine; Histamine Agonists; Histidine; Histone Deacetylase 2; HIV Infections; HIV Reverse Transcriptase; HIV-1; Homebound Persons; Homeodomain Proteins; Homosexuality, Male; Hospice and Palliative Care Nursing; HSP70 Heat-Shock Proteins; Humans; Hyaluronan Receptors; Hydrogen; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemia; Hypoglycemic Agents; Hypoxia; Idiopathic Interstitial Pneumonias; Imaging, Three-Dimensional; Imatinib Mesylate; Immunotherapy; Implementation Science; Incidence; INDEL Mutation; Induced Pluripotent Stem Cells; Industrial Waste; Infant; Infant, Newborn; Inflammation; Inflammation Mediators; Infliximab; Infusions, Intravenous; Inhibitory Concentration 50; Injections; Insecticides; Insulin-Like Growth Factor Binding Protein 5; Insulin-Secreting Cells; Interleukin-1; Interleukin-17; Interleukin-8; Internship and Residency; Intestines; Intracellular Signaling Peptides and Proteins; Ion Transport; Iridaceae; Iridoid Glucosides; Islets of Langerhans Transplantation; Isodon; Isoflurane; Isotopes; Italy; Joint Instability; Ketamine; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Neoplasms; Kinetics; Klebsiella pneumoniae; Knee Joint; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lactate Dehydrogenase 5; Laparoscopy; Laser Therapy; Lasers, Semiconductor; Lasers, Solid-State; Laurates; Lead; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Light; Lipid Peroxidation; Lipopolysaccharides; Liposomes; Liver; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Locomotion; Longitudinal Studies; Lopinavir; Lower Urinary Tract Symptoms; Lubricants; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Lymphoma, Mantle-Cell; Lysosomes; Macrophages; Male; Manganese Compounds; MAP Kinase Kinase 4; Mass Screening; Maternal Health; Medicine, Chinese Traditional; Melanoma, Experimental; Memantine; Membrane Glycoproteins; Membrane Proteins; Mesenchymal Stem Cell Transplantation; Metal Nanoparticles; Metalloendopeptidases; Metalloporphyrins; Methadone; Methane; Methicillin-Resistant Staphylococcus aureus; Mexico; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Nude; Mice, SCID; Mice, Transgenic; Microarray Analysis; Microbial Sensitivity Tests; Microbiota; Micronutrients; MicroRNAs; Microscopy, Confocal; Microsomes, Liver; Middle Aged; Milk; Milk, Human; Minority Groups; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Models, Animal; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Epidemiology; Molecular Structure; Molecular Weight; Multilocus Sequence Typing; Multimodal Imaging; Muscle Strength; Muscle, Skeletal; Muscular Diseases; Mutation; Mycobacterium tuberculosis; Myocardial Stunning; Myristates; NAD(P)H Dehydrogenase (Quinone); Nanocomposites; Nanogels; Nanoparticles; Nanotechnology; Naphthalenes; Nasal Cavity; National Health Programs; Necrosis; Needs Assessment; Neoadjuvant Therapy; Neonicotinoids; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm Transplantation; Neoplasms; Neoplastic Stem Cells; Netherlands; Neuroblastoma; Neuroprotective Agents; Neutrophils; NF-kappa B; NFATC Transcription Factors; Nicotiana; Nicotine; Nitrates; Nitrification; Nitrites; Nitro Compounds; Nitrogen; Nitrogen Dioxide; North Carolina; Nuclear Magnetic Resonance, Biomolecular; Nuclear Proteins; Nucleic Acid Hybridization; Nucleosomes; Nutrients; Obesity; Obesity, Morbid; Oceans and Seas; Oncogene Protein v-akt; Oncogenes; Oocytes; Open Reading Frames; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal; Outpatients; Ovarian Neoplasms; Ovariectomy; Overweight; Oxazines; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxides; Oxidoreductases; Oxygen; Oxygen Inhalation Therapy; Oxygenators, Membrane; Ozone; Paclitaxel; Paenibacillus; Pain Measurement; Palliative Care; Pancreatic Neoplasms; Pandemics; Parasympathetic Nervous System; Particulate Matter; Pasteurization; Patient Preference; Patient Satisfaction; Pediatric Obesity; Permeability; Peroxiredoxins; Peroxynitrous Acid; Pharmaceutical Services; Pharmacists; Pharmacy; Phaseolus; Phenotype; Phoeniceae; Phosphates; Phosphatidylinositol 3-Kinases; Phospholipid Transfer Proteins; Phospholipids; Phosphorus; Phosphorylation; Photoperiod; Photosynthesis; Phylogeny; Physical Endurance; Physicians; Pilot Projects; Piperidines; Pituitary Adenylate Cyclase-Activating Polypeptide; Plant Extracts; Plant Leaves; Plant Proteins; Plant Roots; Plaque, Atherosclerotic; Pneumonia; Pneumonia, Viral; Point-of-Care Testing; Polyethylene Glycols; Polymers; Polysorbates; Pore Forming Cytotoxic Proteins; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postprandial Period; Poverty; Pre-Exposure Prophylaxis; Prediabetic State; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy, High-Risk; Prenatal Exposure Delayed Effects; Pressure; Prevalence; Primary Graft Dysfunction; Primary Health Care; Professional Role; Professionalism; Prognosis; Progression-Free Survival; Prolactin; Promoter Regions, Genetic; Proof of Concept Study; Proportional Hazards Models; Propylene Glycol; Prospective Studies; Prostate; Protein Binding; Protein Biosynthesis; Protein Isoforms; Protein Kinase Inhibitors; Protein Phosphatase 2; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein Transport; Proteoglycans; Proteome; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Proton Pumps; Protons; Protoporphyrins; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Veins; Pyrazoles; Pyridines; Pyrimidines; Qualitative Research; Quinoxalines; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Histamine H3; Receptors, Immunologic; Receptors, Transferrin; Recombinant Proteins; Recurrence; Reference Values; Referral and Consultation; Regional Blood Flow; Registries; Regulon; Renal Insufficiency, Chronic; Reperfusion Injury; Repressor Proteins; Reproducibility of Results; Republic of Korea; Research Design; Resistance Training; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency; Resuscitation; Retinal Dehydrogenase; Retreatment; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Ribosomal Proteins; Ribosomes; Risk Assessment; Risk Factors; Ritonavir; Rivers; RNA Interference; RNA-Seq; RNA, Messenger; RNA, Ribosomal, 16S; RNA, Small Interfering; Rosuvastatin Calcium; Rural Population; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salivary Ducts; Salivary Gland Neoplasms; San Francisco; SARS-CoV-2; Satiation; Satiety Response; Schools; Schools, Pharmacy; Seasons; Seawater; Selection, Genetic; Sequence Analysis, DNA; Serine-Threonine Kinase 3; Sewage; Sheep; Sheep, Domestic; Shock, Hemorrhagic; Signal Transduction; Silver; Silymarin; Single Photon Emission Computed Tomography Computed Tomography; Sirolimus; Sirtuin 1; Skin; Skin Neoplasms; Skin Physiological Phenomena; Sleep Initiation and Maintenance Disorders; Social Class; Social Participation; Social Support; Soil; Soil Microbiology; Solutions; Somatomedins; Soot; Specimen Handling; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Spinal Fractures; Spirometry; Staphylococcus aureus; STAT1 Transcription Factor; STAT3 Transcription Factor; Streptomyces coelicolor; Stress, Psychological; Stroke; Stroke Volume; Structure-Activity Relationship; Students, Medical; Students, Pharmacy; Substance Abuse Treatment Centers; Sulfur Dioxide; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Analysis; Survival Rate; Survivin; Sweden; Swine; Swine, Miniature; Sympathetic Nervous System; T-Lymphocytes, Regulatory; Talaromyces; Tandem Mass Spectrometry; tau Proteins; Telemedicine; Telomerase; Telomere; Telomere Homeostasis; Temperature; Terminally Ill; Th1 Cells; Thiamethoxam; Thiazoles; Thiophenes; Thioredoxin Reductase 1; Thrombosis; Thulium; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Time Factors; Titanium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transcriptome; Transforming Growth Factor beta1; Transistors, Electronic; Translational Research, Biomedical; Transplantation Tolerance; Transplantation, Homologous; Transportation; Treatment Outcome; Tretinoin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Tubulin Modulators; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Twins; Ultrasonic Therapy; Ultrasonography; Ultraviolet Rays; United States; Up-Regulation; Uranium; Urethra; Urinary Bladder; Urodynamics; Uromodulin; Uveitis; Vasoconstrictor Agents; Ventricular Function, Left; Vero Cells; Vesicular Transport Proteins; Viral Nonstructural Proteins; Visual Acuity; Vital Capacity; Vitamin D; Vitamin D Deficiency; Vitamin K 2; Vitamins; Volatilization; Voriconazole; Waiting Lists; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Whole Genome Sequencing; Wine; Wnt Signaling Pathway; Wound Healing; Wounds and Injuries; WW Domains; X-linked Nuclear Protein; X-Ray Diffraction; Xanthines; Xenograft Model Antitumor Assays; YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

We present three patients affected by pulmonary squamous cell carcinoma, metastatic esophageal cancer and advanced non-Hodgkin lymphoma, who incurred in coronavirus 2019 (COVID-19) infection during the early phase of epidemic wave in Italy. All patients presented with fever. Social contact with subject positive for COVID-19 was declared in only one of the three cases. In all cases, laboratory findings showed lymphopenia and elevated C-reactive protein (CRP). Chest x-ray and computed tomography showed bilateral ground-glass opacities, shadowing, interstitial abnormalities, and "crazy paving" pattern which evolved with superimposition of consolidations in one patient. All patients received antiviral therapy based on ritonavir and lopinavir, associated with hydroxychloroquine. Despite treatment, two patients with advanced cancers died after 39 and 17 days of hospitalization, while the patient with lung cancer was dismissed at home, in good conditions.

Topics: Aged; Anti-Bacterial Agents; Antiviral Agents; Betacoronavirus; Carcinoma, Squamous Cell; Coronavirus Infections; COVID-19; Disease Outbreaks; Drug Therapy, Combination; Esophageal Neoplasms; Fatal Outcome; Humans; Hydroxychloroquine; Italy; Lopinavir; Lung Neoplasms; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasms; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome

As of January 22, 2020, a total of 571 cases of the 2019-new coronavirus (2019-nCoV) have been reported in 25 provinces (districts and cities) in China. At present, there is no vaccine or antiviral treatment for human and animal coronavirus, so that identifying the drug treatment options as soon as possible is critical for the response to the 2019-nCoV outbreak. Three general methods, which include existing broad-spectrum antiviral drugs using standard assays, screening of a chemical library containing many existing compounds or databases, and the redevelopment of new specific drugs based on the genome and biophysical understanding of individual coronaviruses, are used to discover the potential antiviral treatment of human pathogen coronavirus. Lopinavir /Ritonavir, Nucleoside analogues, Neuraminidase inhibitors, Remdesivir, peptide (EK1), abidol, RNA synthesis inhibitors (such as TDF, 3TC), anti-inflammatory drugs (such as hormones and other molecules), Chinese traditional medicine, such ShuFengJieDu Capsules and Lianhuaqingwen Capsule, could be the drug treatment options for 2019-nCoV. However, the efficacy and safety of these drugs for 2019- nCoV still need to be further confirmed by clinical experiments.

Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Discovery; Humans; Lopinavir; Neuraminidase; Nucleosides; Pneumonia, Viral; Ribonucleotides; Ritonavir; SARS-CoV-2

Topics: Adult; Antiviral Agents; Betacoronavirus; China; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drugs, Chinese Herbal; Female; Humans; Indoles; Lopinavir; Male; Middle Aged; Pneumonia, Viral; Retrospective Studies; Ritonavir; SARS-CoV-2; Young Adult

Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.

Topics: Betacoronavirus; China; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Testing; COVID-19 Vaccines; Cytochrome P-450 CYP3A Inhibitors; Drug Combinations; Humans; Lopinavir; Male; Middle Aged; Pneumonia; Pneumonia, Viral; Real-Time Polymerase Chain Reaction; Republic of Korea; Ritonavir; SARS-CoV-2; Viral Load

Topics: Adenosine Monophosphate; Alanine; Animals; Anti-HIV Agents; Betacoronavirus; China; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; COVID-19; COVID-19 Serotherapy; Dioxanes; Disease Models, Animal; Drug Combinations; Humans; Immunization, Passive; Lopinavir; Medicine, Chinese Traditional; Monosaccharides; Pandemics; Pneumonia, Viral; Registries; Ritonavir; SARS-CoV-2; Severe Acute Respiratory Syndrome; Stem Cell Transplantation; Steroids; Time Factors; Treatment Outcome; World Health Organization

Topics: Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; Humans; Lopinavir; Pandemics; Pneumonia; Pneumonia, Viral; Republic of Korea; Reverse Transcriptase Polymerase Chain Reaction; Ritonavir; SARS-CoV-2

Topics: Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; Humans; Lopinavir; Pandemics; Pneumonia; Pneumonia, Viral; Republic of Korea; Reverse Transcriptase Polymerase Chain Reaction; Ritonavir; SARS-CoV-2

新型冠状病毒肺炎治疗药物洛匹那韦/利托那韦（LPV/r）是多种细胞色素P(450)（CYP(450)）酶的抑制剂，又是多种CYP(450)酶底物，此外还是P-糖蛋白的抑制剂、葡萄糖醛酸转移酶诱导剂，与很多抗肿瘤药物存在药物相互作用。药品说明书仅列举了少数抗肿瘤药物与LPV/r的相互作用，提供参考信息严重不足。本文系统总结了抗肿瘤药物及常用辅助药物和LPV/r的相互作用及处理建议。.

Topics: Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Interactions; Drug Monitoring; Humans; Lopinavir; Neoplasms; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China.. To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management.. Descriptive case series of the first 18 patients diagnosed with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection at 4 hospitals in Singapore from January 23 to February 3, 2020; final follow-up date was February 25, 2020.. Confirmed SARS-CoV-2 infection.. Clinical, laboratory, and radiologic data were collected, including PCR cycle threshold values from nasopharyngeal swabs and viral shedding in blood, urine, and stool. Clinical course was summarized, including requirement for supplemental oxygen and intensive care and use of empirical treatment with lopinavir-ritonavir.. Among the 18 hospitalized patients with PCR-confirmed SARS-CoV-2 infection (median age, 47 years; 9 [50%] women), clinical presentation was an upper respiratory tract infection in 12 (67%), and viral shedding from the nasopharynx was prolonged for 7 days or longer among 15 (83%). Six individuals (33%) required supplemental oxygen; of these, 2 required intensive care. There were no deaths. Virus was detectable in the stool (4/8 [50%]) and blood (1/12 [8%]) by PCR but not in urine. Five individuals requiring supplemental oxygen were treated with lopinavir-ritonavir. For 3 of the 5 patients, fever resolved and supplemental oxygen requirement was reduced within 3 days, whereas 2 deteriorated with progressive respiratory failure. Four of the 5 patients treated with lopinavir-ritonavir developed nausea, vomiting, and/or diarrhea, and 3 developed abnormal liver function test results.. Among the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore, clinical presentation was frequently a mild respiratory tract infection. Some patients required supplemental oxygen and had variable clinical outcomes following treatment with an antiretroviral agent.

Topics: Adult; Aged; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Disease Progression; Drug Combinations; Female; Humans; Lopinavir; Male; Middle Aged; Oxygen Inhalation Therapy; Pandemics; Pneumonia, Viral; Polymerase Chain Reaction; Respiratory Tract Infections; Ritonavir; SARS-CoV-2; Singapore; Virus Shedding

Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Humans; Lopinavir; Lung; Lung Neoplasms; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed

Topics: Anti-HIV Agents; Betacoronavirus; China; Clinical Laboratory Techniques; Coinfection; Coronavirus Infections; COVID-19; COVID-19 Testing; Diabetes Mellitus, Type 2; Drug Combinations; gamma-Globulins; HIV; HIV Infections; Humans; Lopinavir; Male; Methylprednisolone; Middle Aged; Moxifloxacin; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has become an important public health issue in the world. More than 118 000 cases were confirmed around the world. The main clinical manifestations were respiratory symptoms and occasional gastrointestinal symptoms. However, there is no unified standard for the diagnosis and treatment of COVID-19. In the retrospective analysis, we report nine cases of COVID-19, describe the history of contact, clinical manifestations, the course of diagnosis and clinical treatment before, during and after treatment.

Topics: Adolescent; Adult; Betacoronavirus; China; Clinical Laboratory Techniques; Contact Tracing; Coronavirus Infections; COVID-19; COVID-19 Testing; Female; Humans; Interferon alpha-2; Lopinavir; Male; Methylprednisolone; Middle Aged; Moxifloxacin; Oropharynx; Oxygen; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; RNA, Viral; SARS-CoV-2; Severity of Illness Index; T-Lymphocytes; Tomography, X-Ray Computed

The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains-severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir/ritonavir, lopinavir/ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.. 2019新型冠状病毒（2019-nCoV）是武汉不明原因肺炎的致病原。2019-nCoV在遗传学上与一种蝙蝠来源的新型冠状病毒比较接近，与SARS-CoⅤ、MERS-CoV同为β属冠状病毒。目前临床上常用的抗病毒药物，包括神经氨酸酶抑制剂（奥司他韦、帕拉米韦、扎那米韦等）、更昔洛韦、阿昔洛韦、利巴韦林等药物对2019-nCoV均无效，不建议临床应用。目前研究证实可能有效的药物包括：瑞德西韦、洛匹那韦/利托那韦、洛匹那韦/利托那韦联合干扰素-β、恢复期血浆、单克隆抗体。但这些药物在2019-nCoV肺炎患者中的疗效和安全性有待进一步临床实验证实。.

Topics: Antibodies, Monoclonal; Antiviral Agents; Betacoronavirus; China; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytochrome P-450 CYP3A Inhibitors; Humans; Interferon-beta; Lopinavir; Middle East Respiratory Syndrome Coronavirus; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Severe Acute Respiratory Syndrome

Corona Virus Disease 2019 (COVID-19) due to the 2019 novel coronavirus (SARS-CoV-2) emerged in Wuhan city and rapidly spread throughout China. We aimed to compare arbidol and lopinavir/ritonavir(LPV/r) treatment for patients with COVID-19 with LPV/r only.. In this retrospective cohort study, we included adults (age≥18years) with laboratory-confirmed COVID-19 without Invasive ventilation, diagnosed between Jan 17, 2020, and Feb 13, 2020. Patients, diagnosed after Jan 17, 2020, were given oral arbidol and LPV/r in the combination group and oral LPV/r only in the monotherapy group for 5-21 days. The primary endpoint was a negative conversion rate of coronavirus from the date of COVID-19 diagnosis(day7, day14), and assessed whether the pneumonia was progressing or improving by chest CT (day7).. We analyzed 16 patients who received oral arbidol and LPV/r in the combination group and 17 who oral LPV/r only in the monotherapy group, and both initiated after diagnosis. Baseline clinical, laboratory, and chest CT characteristics were similar between groups. The SARS-CoV-2 could not be detected for 12(75%) of 16 patients' nasopharyngeal specimens in the combination group after seven days, compared with 6 (35%) of 17 in the monotherapy group (p < 0·05). After 14 days, 15 (94%) of 16 and 9 (52·9%) of 17, respectively, SARS-CoV-2 could not be detected (p < 0·05). The chest CT scans were improving for 11(69%) of 16 patients in the combination group after seven days, compared with 5(29%) of 17 in the monotherapy group (p < 0·05).. In patients with COVID-19, the apparent favorable clinical response with arbidol and LPV/r supports further LPV/r only.

Topics: Administration, Oral; Adult; Antiviral Agents; Cohort Studies; Coronavirus Infections; COVID-19; Drug Combinations; Drug Therapy, Combination; Female; Humans; Indoles; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; Tomography, X-Ray Computed

An epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread unexpectedly in Wuhan, Hubei Province, China, since December 2019. There are few reports about asymptomatic contacts of infected patients identified as positive for SARS-CoV-2 through screening. We studied the epidemiological and clinical outcomes in 55 asymptomatic carriers who were laboratory confirmed to be positive for SARS-CoV-2 through nucleic acid testing of pharyngeal swab samples. The asymptomatic carriers seldom occurred among young people (aged 18-29 years) who had close contact with infected family members. In the majority of patients, the outcome was mild or ordinary 2019 novel coronavirus disease during hospitalization.

Topics: Adolescent; Adult; Aged; Antiviral Agents; Asymptomatic Infections; Betacoronavirus; Child; Child, Preschool; China; Coronavirus Infections; COVID-19; Disease Progression; Drug Combinations; Female; Hospitalization; Humans; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; SARS-CoV-2; Time Factors; Treatment Outcome; Young Adult

Topics: Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Adenine; Adenosine Monophosphate; Alanine; Amides; Antimalarials; Antiviral Agents; Betacoronavirus; China; Chloroquine; Clinical Trials as Topic; Cobicistat; Coronavirus 3C Proteases; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cysteine Endopeptidases; Dibenzothiepins; Drug Combinations; Drug Discovery; Drug Therapy, Combination; Emtricitabine; Humans; Hydroxychloroquine; Indoles; Lopinavir; Medicine, Chinese Traditional; Morpholines; Oseltamivir; Oxazines; Pandemics; Pneumonia, Viral; Pyrazines; Pyridines; Pyridones; Ritonavir; RNA-Dependent RNA Polymerase; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Tenofovir; Thiepins; Triazines; Viral Nonstructural Proteins

The outbreak of the novel coronavirus in China (SARS-CoV-2) that began in December 2019 presents a significant and urgent threat to global health. This study was conducted to provide the international community with a deeper understanding of this new infectious disease. Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study. A total of 135 hospitalized patients with COVID-19 were enrolled. The median age was 47 years (interquartile range, 36-55), and there was no significant gender difference (53.3% men). The majority of patients had contact with people from the Wuhan area. Forty-three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]). Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]). Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients. All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]). In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]). It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines. Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d-dimer, lactate dehydrogenase, PCT, ALB, C-reactive protein, and aspartate aminotransferase. This study demonstrates the clinic features and therapies of 135 COVID-19 patients. Kaletra and TCM played an important role in the treatment of the viral pneumonia. Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID-19.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Bacterial Agents; Antiviral Agents; Betacoronavirus; Biomarkers; Cardiovascular Diseases; China; Clinical Laboratory Techniques; Coronavirus Infections; Cough; COVID-19; COVID-19 Testing; Diabetes Complications; Diabetes Mellitus; Drug Combinations; Drugs, Chinese Herbal; Fatigue; Female; Fever; Humans; Interferons; Lopinavir; Male; Middle Aged; Neoplasms; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; SARS-CoV-2; Severity of Illness Index; Tomography, X-Ray Computed

Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Betacoronavirus; Biomedical Research; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Humans; Hydroxychloroquine; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; World Health Organization

This study aims to evaluate the correlation between viral clearance and blood biochemical index of 94 discharged patients with COVID-19 infection in Shenzhen Third People's Hospital, enrolled from Jan 5 to Feb 13, 2020.. The clinical and laboratory findings were extracted from the electronic medical records of the patients. The data were analysed and reviewed by a trained team of physicians. Information on clinical signs and symptoms, medical treatment, virus clearance, and laboratory parameters including interleukin 6 (IL-6) and C-reactive protein were collected.. COVID-19 mRNA clearance ratio was identified significantly correlated with the decline of serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, COVID-19 mRNA clearance time was positively correlated with the length of hospital stay in patients treated with either IFN-α + lopinavir/ritonavir or IFN-α + lopinavir/ritonavir + ribavirin.. Therapeutic regimens of IFN-α + lopinavir/ritonavir and IFN-α + lopinavir/ritonavir + ribavirin might be beneficial for treatment of COVID-19. Serum LDH or CK decline may predict a favorable response to treatment of COVID-19 infection.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; China; Coronavirus Infections; COVID-19; Creatine Kinase; Drug Combinations; Humans; Interferon-alpha; L-Lactate Dehydrogenase; Lopinavir; Middle Aged; Pandemics; Pneumonia, Viral; Polymerase Chain Reaction; Retrospective Studies; Ritonavir; RNA, Viral; Young Adult

Topics: Aged; Betacoronavirus; Cobicistat; Colchicine; Coronavirus Infections; COVID-19; Cytokines; Darunavir; Drug Combinations; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lopinavir; Male; Middle Aged; Mycophenolic Acid; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tacrolimus; Transplant Recipients; Treatment Outcome

Topics: Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Drug Combinations; Endocytosis; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Antiviral Agents; Betacoronavirus; Communicable Disease Control; Coronavirus Infections; COVID-19; Disease Management; Disease Transmission, Infectious; Humans; Hydroxychloroquine; Lopinavir; Mediterranean Region; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Treatment Outcome

The Coronavirus disease 2019 (COVID-19) which outbroke in December 2019 is highly contagious with a low cure rate. In view of this, there is an urgent need to find a more appropriate therapeutic scheme against COVID-19. The study aimed to investigate whether lopinavir/ritonavir (LPV/r) in combination with other pneumonia-associated adjuvant drugs has a better therapeutic effect on COVID-19.. Totally 47 patients with COVID-19 infection who were admitted to Rui'an People's Hospital between January 22 and January 29, 2020 were collected. The patients were divided into the test group and the control group according to whether they had been treated with LPV/r or not during hospitalization. Patients in the test group were treated with LPV/r combined with adjuvant medicine, while those in the control group were just treated with adjuvant medicine. The changes of body temperature, blood routine and blood biochemistry between the two groups were observed and compared.. Both groups achieved good therapeutic effect with the body temperature of patients decreased gradually from admission to the 10th day of treatment. But the body temperature of patients in the test group decreased faster than that of the control group. Blood routine indexes showed that compared with the control group, the abnormal proportion of white blood cells, lymphocytes and C-reactive protein of the test group could be reduced to some extent. Blood biochemical indexes exhibited that the proportion of patients with abnormal alanine aminotransferase and aspartate aminotransferase in the test group were lower than the control group. The number of days for nCoV-RNA turning negative after treatment was significantly decreased in the test group than that in the control group.. Compared with the treatment of pneumonia-associated adjuvant drugs alone, the combination treatment with LPV/r and adjuvant drugs has a more evident therapeutic effect in lowering the body temperature and restoring normal physiological mechanisms with no evident toxic and side effects. In view of these conclusions, we suggested that the use of LPV/r combined with pneumonia-associated adjuvant drugs in the clinical treatment for patients with COVID-19 should be promoted.

Topics: Adolescent; Betacoronavirus; Child; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Female; Fever; Humans; Lopinavir; Male; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Adult; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis.. A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization.. COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.

Topics: Acute Disease; Antiviral Agents; Bacteroides Infections; Betacoronavirus; Biomarkers; Candidiasis; Coronavirus Infections; COVID-19; Drug Combinations; Echocardiography; Fatal Outcome; Humans; Interleukin-6; Lopinavir; Male; Middle Aged; Myocarditis; Pandemics; Piperacillin, Tazobactam Drug Combination; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Stroke Volume; Tomography, X-Ray Computed; Troponin I

An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in Wuhan, China, with cases now confirmed in multiple countries. The clinical course of patients remains to be fully characterized, clinical presentation ranges from asymptomatic infection to acute respiratory distress syndrome and acute renal failure, and no pharmacological therapies of proven efficacy yet exist. We report a case of SARS-CoV-2 infection in a renal transplant recipient with excellent outcome. This case states the importance of close monitoring of the concentration of cyclosporine in patients treated with lopinavir/ritonavir; the routine treatment of corticosteroid can be continued. This is a rare report of SARS-CoV-2 infection in a renal transplant recipient. Further data are needed to achieve better understanding of the impact of immunosuppressive therapy on the clinical presentation, severity, and outcome of SARS-CoV-2 infections in solid organ transplant recipients.

Topics: Adrenal Cortex Hormones; Adult; Betacoronavirus; China; Coronavirus Infections; COVID-19; Cyclosporine; Disease Outbreaks; Drug Combinations; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Lopinavir; Male; Pandemics; Pneumonia, Viral; Reverse Transcriptase Polymerase Chain Reaction; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed; Transplant Recipients; Treatment Outcome

During the novel coronavirus pandemic, organ transplant recipients represent a frail susceptible category due to long-term immunosuppressive therapy. For this reason, clinical manifestations may differ from general population and different treatment approaches may be needed. We present the case of a 36-year-old kidney-transplanted woman affected by Senior-Loken syndrome diagnosed with COVID-19 pneumonia after a contact with her positive mother. Initial symptoms were fatigue, dry cough, and coryza; she never had fever nor oxygen supplementation. Hydroxychloroquine and lopinavir/ritonavir were started, and the antiviral drug was replaced with darunavir/cobicistat after 2 days for diarrhea. Immunosuppressant levels were closely monitored, and we observed very high tacrolimus trough levels despite initial dose reduction. The patient was left with steroid therapy alone. The peculiarity of clinical presentation and the management difficulties represent the flagship of our case report. We stress the need for guidelines in transplant recipients with COVID-19 infection with particular regard to the management of therapy.

Topics: Adult; Antiviral Agents; Betacoronavirus; C-Reactive Protein; Ciliopathies; Cobicistat; Common Cold; Coronavirus Infections; Cough; COVID-19; COVID-19 Drug Treatment; Cytochrome P-450 CYP3A Inhibitors; Darunavir; Deprescriptions; Drug Combinations; Drug Interactions; Enzyme Inhibitors; Fatigue; Female; Glucocorticoids; Graft Rejection; Humans; Hydroxychloroquine; Immunocompromised Host; Immunosuppressive Agents; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Kidney Diseases, Cystic; Kidney Failure, Chronic; Kidney Transplantation; Leber Congenital Amaurosis; Lopinavir; Methylprednisolone; Optic Atrophies, Hereditary; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Severity of Illness Index; Tacrolimus

Lopinavir/ritonavir and arbidol have been previously used to treat acute respiratory syndrome- coronavirus 2 (SARS-CoV-2) replication in clinical practice; nevertheless, their effectiveness remains controversial. In this study, we evaluated the antiviral effects and safety of lopinavir/ritonavir and arbidol in patients with the 2019-nCoV disease (COVID-19). Fifty patients with laboratory-confirmed COVID-19 were divided into two groups: including lopinavir/ritonavir group (34 cases) and arbidol group (16 cases). Lopinavir/ritonavir group received 400 mg/100mg of Lopinavir/ritonavir, twice a day for a week, while the arbidol group was given 0.2 g arbidol, three times a day. Data from these patients were retrospectively analyzed. The cycle threshold values of open reading frame 1ab and nucleocapsid genes by RT-PCR assay were monitored during antiviral therapy. None of the patients developed severe pneumonia or ARDS. There was no difference in fever duration between the two groups (P=0.61). On day 14 after the admission, no viral load was detected in arbidol group, but the viral load was found in 15(44.1%) patients treated with lopinavir/ritonavir. Patients in the arbidol group had a shorter duration of positive RNA test compared to those in the lopinavir/ritonavir group (P<0.01). Moreover, no apparent side effects were found in both groups. In conclusion, our data indicate that arbidol monotherapy may be superior to lopinavir/ritonavir in treating COVID-19.

Topics: Adult; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Female; Humans; Indoles; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; SARS-CoV-2; Viral Load

Some patients with SARS-CoV-2 infection have abnormal liver function. We aimed to clarify the features of COVID-19-related liver damage to provide references for clinical treatment.. We performed a retrospective, single-center study of 148 consecutive patients with confirmed COVID-19 (73 female, 75 male; mean age, 50 years) at the Shanghai Public Health Clinical Center from January 20 through January 31, 2020. Patient outcomes were followed until February 19, 2020. Patients were analyzed for clinical features, laboratory parameters (including liver function tests), medications, and length of hospital stay. Abnormal liver function was defined as increased levels of alanine and aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, and total bilirubin.. Fifty-five patients (37.2%) had abnormal liver function at hospital admission; 14.5% of these patients had high fever (14.5%), compared with 4.3% of patients with normal liver function (P = .027). Patients with abnormal liver function were more likely to be male, and had higher levels of procalcitonin and C-reactive protein. There was no statistical difference between groups in medications taken before hospitalization; a significantly higher proportion of patients with abnormal liver function (57.8%) had received lopinavir/ritonavir after admission compared to patients with normal liver function (31.3%). Patients with abnormal liver function had longer mean hospital stays (15.09 ± 4.79 days) than patients with normal liver function (12.76 ± 4.14 days) (P = .021).. More than one third of patients admitted to the hospital with SARS-CoV-2 infection have abnormal liver function, and this is associated with longer hospital stay. A significantly higher proportion of patients with abnormal liver function had received lopinavir/ritonavir after admission; these drugs should be given with caution.

Topics: Adult; Antiviral Agents; Betacoronavirus; Bilirubin; Blood Chemical Analysis; China; Coronavirus Infections; COVID-19; Enzymes; Female; Hospitals; Humans; Liver Diseases; Liver Function Tests; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prevalence; Retrospective Studies; Ritonavir; SARS-CoV-2

Here we report on the most recent updates on experimental drugs successfully employed in the treatment of the disease caused by SARS-CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease-19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir [which is widely used to treat Human Immunodeficiency Virus (HIV) infection] in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxychloroquine, favipiravir and co-administered darunavir and umifenovir (in patient therapies) were also recently recorded as having anti-SARS-CoV-2 effects. Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experimental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this virus. This also stresses the urgent need for the scientific community to devote its efforts to the development of other more specific antiviral strategies.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; China; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Darunavir; Drug Combinations; Humans; Hydroxychloroquine; Indoles; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; SARS-CoV-2

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Drug Repositioning; Humans; Hydroxychloroquine; Lopinavir; Pandemics; Pneumonia, Viral; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Ritonavir; Sample Size; SARS-CoV-2; United States

The COVID-19 pandemic has led to efforts at rapid investigation and application of drugs which may improve prognosis but for which safety and efficacy are not yet established. This document attempts to provide reasonable guidance for the use of antimicrobials which have uncertain benefit but may increase risk of QT interval prolongation and ventricular proarrhythmia, notably, chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir. During the pandemic, efforts to reduce spread and minimize effects on health care resources mandate minimization of unnecessary medical procedures and testing. We recommend that the risk of drug proarrhythmia be minimized by 1) discontinuing unnecessary medications that may also increase the QT interval, 2) identifying outpatients who are likely to be at low risk and do not need further testing (no history of prolonged QT interval, unexplained syncope, or family history of premature sudden cardiac death, no medications that may prolong the QT interval, and/or a previous known normal corrected QT interval [QTc]), and 3) performing baseline testing in hospitalized patients or those who may be at higher risk. If baseline electrocardiographic testing reveals a moderately prolonged QTc, optimization of medications and electrolytes may permit therapy. If the QTc is markedly prolonged, drugs that further prolong it should be avoided, or expert consultation may permit administration with mitigating precautions. These recommendations are made while there are no known effective treatments for COVID-19 and should be revisited when further data on efficacy and safety become available.

Topics: Antiviral Agents; Arrhythmias, Cardiac; Azithromycin; Betacoronavirus; Canada; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Long QT Syndrome; Pandemics; Pneumonia, Viral; Risk Management; Ritonavir; SARS-CoV-2

The clinical characteristics, management, and outcome of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after solid organ transplant (SOT) remain unknown. We report our preliminary experience with 18 SOT (kidney [44.4%], liver [33.3%], and heart [22.2%]) recipients diagnosed with COVID-19 by March 23, 2020 at a tertiary-care center at Madrid. Median age at diagnosis was 71.0 ± 12.8 years, and the median interval since transplantation was 9.3 years. Fever (83.3%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (72.2%) were the most common presentations. Lopinavir/ritonavir (usually associated with hydroxychloroquine) was used in 50.0% of patients and had to be prematurely discontinued in 2 of them. Other antiviral regimens included hydroxychloroquine monotherapy (27.8%) and interferon-β (16.7%). As of April 4, the case-fatality rate was 27.8% (5/18). After a median follow-up of 18 days from symptom onset, 30.8% (4/13) of survivors developed progressive respiratory failure, 7.7% (1/13) showed stable clinical condition or improvement, and 61.5% (8/13) had been discharged home. C-reactive protein levels at various points were significantly higher among recipients who experienced unfavorable outcome. In conclusion, this frontline report suggests that SARS-CoV-2 infection has a severe course in SOT recipients.

Topics: Aged; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Female; Fever; Humans; Hydroxychloroquine; Immunosuppressive Agents; Interferon-beta; Lopinavir; Male; Middle Aged; Organ Transplantation; Pandemics; Pneumonia, Viral; Radiography, Thoracic; Retrospective Studies; Ritonavir; SARS-CoV-2; Spain; Transplant Recipients

We present the report of the first, to our best knowledge, case of COVID-19 in a tetraplegic person.. A 56-year-old male with AIS A C4 tetraplegia developed fever during the night, without any prodrome. His general practitioner suspected a urinary tract infection and prescribed him antibiotic therapy. After 2 days of antibiotic therapy the fever still persisted, so the individual was admitted to the local hospital and treated with broad-spectrum antibiotics. After 2 days he was transferred to our spinal unit. Considering the worsening of the chest X-ray and fever despite 48 h of broad-spectrum antibiotic therapy, we strongly suspected viral pneumonia. SARS-CoV-2 was detected and antiviral therapy with Lopinavir/Ritonavir, associated with hydroxychloroquine, was promptly started. Fever ceased after 2 days of therapy.. Blood test and chest X-ray findings in this patient were similar to previously published findings regarding COVID-19. One difference between this case and the known clinical course of COVID-19 is that did not develop cough. Another interesting feature of our case is that, despite tetraplegia, the clinical course was not severe. Persons with COVID-19 remain asymptomatic, these results underscore the need for rehabilitation and SCI professionals to have a high index of suspicion for COVID-19 in their inpatient and outpatient clients. Only inpatient with fever hase being tested for COVID-19. All new patients are submitted to SARS-COV-2 Test. Moreover, routine testing of patients who have to participate in therapy in common gym areas may be warranted.

Topics: Anti-Bacterial Agents; Anti-Retroviral Agents; Clinical Laboratory Techniques; Coronavirus Infections; Cough; COVID-19; COVID-19 Testing; Fever; Hospitalization; Humans; Italy; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Quadriplegia; Respiration, Artificial; Ritonavir; Severe acute respiratory syndrome-related coronavirus; Spinal Cord Injuries

Topics: Adult; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

In December 2019, numerous coronavirus disease 2019 (COVID-19) cases were reported in Wuhan, China, which has since spread throughout the world. However, its impact on rheumatoid arthritis (RA) patients is unknown. Herein, we report a case of COVID-19 pneumonia in a 61-year-old female RA patient who was receiving conventional disease-modifying antirheumatic drugs (cDMARDs). The patient presented with a 4-day history of myalgia and febrile sensation. COVID-19 was confirmed by real-time polymerase chain reaction (PCR). Chest X-ray showed increased opacity on the right lower lung area, and C-reactive protein level was slightly elevated. The patient was treated with antiviral agents (lopinavir/ritonavir), and treatment with cDMARDs was discontinued except hydroxychloroquine. Her symptoms and laboratory results gradually improved. Three weeks later, real-time PCR for COVID-19 showed negative conversion, and the patient was discharged without any complications.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; China; Coronavirus Infections; COVID-19; Drug Combinations; Female; Humans; Hydroxychloroquine; Immunocompromised Host; Lopinavir; Middle Aged; Pandemics; Pneumonia, Viral; Real-Time Polymerase Chain Reaction; Ritonavir; Treatment Outcome

An ongoing outbreak of a novel coronavirus disease (coronavirus disease 2019, COVID-19) has become a global threat. While clinical reports from China to date demonstrate that the majority of cases remain relatively mild and recover with supportive care, it is also crucial to be well prepared for severe cases warranting intensive care. Initiating appropriate infection control measures may not always be achievable in primary care or in acute-care settings.. A 45-year-old man was admitted to the intensive care unit due to severe pneumonia, later confirmed as COVID-19. His initial evaluation in the resuscitation room and treatments in the intensive care unit was performed under droplet and contact precaution with additional airborne protection using the N95 respirator mask. He was successfully treated in the intensive care unit with mechanical ventilation and extracorporeal membrane oxygenation for respiratory support; and antiretroviral treatment with lopinavir/ritonavir. His total intensive care unit stay was 15 days and was discharged on hospital day 24.. Strict infection control precautions are not always an easy task, especially under urgent care in an intensive care unit. However, severe cases of COVID-19 pneumonia, or another novel infectious disease, could present at any moment and would be a continuing challenge to pursue appropriate measures. We need to be well prepared to secure healthcare workers from exposure to infectious diseases and nosocomial spread, as well as to provide necessary intensive care.

Topics: Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Critical Care; Drug Combinations; Extracorporeal Membrane Oxygenation; Humans; Infection Control; Japan; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Respiration, Artificial; Ritonavir; SARS-CoV-2

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Alanine; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Azithromycin; Betacoronavirus; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; Drug Combinations; Drug Repositioning; Humans; Hydroxychloroquine; Immunization, Passive; Lopinavir; Neuraminidase; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Betacoronavirus; Coronavirus Infections; COVID-19; Darunavir; HIV Infections; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Republic of Korea; Reverse Transcriptase Polymerase Chain Reaction; Ritonavir; SARS-CoV-2

Topics: Age Factors; Aged; Betacoronavirus; China; Coronavirus Infections; COVID-19; Critical Illness; Drug Therapy, Combination; Glucocorticoids; Hospital Mortality; Humans; Lorazepam; Lymphopenia; Middle Aged; Multiple Organ Failure; Pandemics; Pneumonia, Viral; Proportional Hazards Models; Risk Factors; Ritonavir; SARS-CoV-2

Antiviral drugs are administered in patients with severe COVID-19 respiratory syndrome, including those treated with direct oral anticoagulants (DOACs). Concomitant administration of antiviral agents has the potential to increase their plasma concentration. A series of patients managed in the Cremona Thrombosis Center were admitted at Cremona Hospital for SARS-CoV-2 and started antiviral drugs without stopping DOAC therapy. DOAC plasma levels were measured in hospital and results compared with those recorded before hospitalization.. All consecutive patients on DOACs were candidates for administration of antiviral agents (lopinavir, ritonavir, or darunavir). Plasma samples for DOAC measurement were collected 2to 4 days after starting antiviral treatment, at 12 hours from the last dose intake in patients on dabigatran and apixaban, and at 24 hours in those on rivaroxaban and edoxaban. For each patient, C-trough DOAC level, expressed as ng/mL, was compared with the one measured before hospitalization.. Of the 1039 patients hospitalized between February 22 and March 15, 2020 with COVID-19 pneumonia and candidates for antiviral therapy, 32 were on treatment with a DOAC. DOAC was stopped in 20 and continued in the remaining 12. On average, C-trough levels were 6.14 times higher during hospitalization than in the pre-hospitalization period.. DOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels. In order to prevent bleeding complications, we believe that physicians should consider withholding DOACs from patients with SARS-CoV-2 and replacing them with alternative parenteral antithrombotic strategies for as long as antiviral agents are deemed necessary and until discharge.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antithrombins; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Dabigatran; Darunavir; Drug Interactions; Drug Monitoring; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Italy; Lopinavir; Male; Pandemics; Patient Safety; Pneumonia, Viral; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Risk Factors; Ritonavir; SARS-CoV-2; Severity of Illness Index; Thiazoles

An increase of Ct values was 0.9 per day in 2 cases of COVID-19 treated with lopinavir/ritonavir (LPV/r), an increase was 1.0 per day in 3 cases without LPV/r through illness day 1-10, indicating that LPV/r did not shorten the duration of SARS CoV-2 shedding.

Topics: Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Drug Combinations; Female; Humans; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ribavirin; Ritonavir; SARS-CoV-2; Taiwan; Virus Shedding

The current coronavirus disease 2019 (COVID-19) pandemic requires extra attention for immunocompromised patients, including solid organ transplant recipients. We report on a case of a 35-year-old renal transplant recipient who suffered from a severe COVID-19 pneumonia. The clinical course was complicated by extreme overexposure to the mammalian target of rapamycin inhibitor everolimus, following coadministration of chloroquine and lopinavir/ritonavir therapy. The case is illustrative for dilemmas that transplant professionals may face in the absence of evidence-based COVID-19 therapy and concurrent pressure for exploration of experimental pharmacological treatment options. However, the risk-benefit balance of experimental or off-label therapy may be weighed differently in organ transplant recipients than in otherwise healthy COVID-19 patients, owing to their immunocompromised status and potential drug interactions with immunosuppressive therapy. With this case report, we aimed to achieve increased awareness and improved management of drug-drug interactions associated with the various treatment options for COVID-19 in renal transplant patients.

Topics: Adult; Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Drug Combinations; Drug Interactions; Everolimus; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lopinavir; Male; Netherlands; Pandemics; Pneumonia, Viral; Radiography, Thoracic; Ritonavir; SARS-CoV-2; Transplant Recipients; Treatment Outcome

The fatality of novel coronavirus disease 2019 (COVID-19) is precipitously increased in patients with underlying comorbidities or elderly people. Kidney transplant (KT) recipients are one of the vulnerable populations for infection. COVID-19 infection in KT recipients might be a complicated and awkward situation, but there has been a lack of reports concerning this group. Herein, we demonstrated two distinct cases with different clinical progress. The first case was a 36-year-old man who underwent KT 3 years ago. He was diagnosed with COVID-19 expressing relevant symptoms. Following administration of lopinavir/ritonavir and hydroxychloroquine with reduced immunosuppressant, he recovered from COVID-19. However, the unexpected fluctuations in tacrolimus trough levels needed to be managed because of drug-to-drug interaction. The second case was developed in a 56-year-old man without any symptoms. He received a second KT from an ABO-incompatible donor 8 years ago. He was diagnosed with COVID-19 by screening due to exposure history. During the hospitalization period, the chest infiltrative lesion showed a wax and wane, but he successfully recovered by administration of hydroxychloroquine with azithromycin. These apparently different cases suggest that assertive screening and management could improve the clinical course. In addition, antiviral agents should be used cautiously, especially in patients on calcineurin inhibitors.

Topics: Adult; Antiviral Agents; Azithromycin; Betacoronavirus; Calcineurin Inhibitors; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Interactions; Humans; Hydroxychloroquine; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tacrolimus; Transplant Recipients

Topics: Antiviral Agents; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Testing; Drug Combinations; Female; Humans; Lopinavir; Middle Aged; Pandemics; Patient Discharge; Pneumonia, Viral; Ribavirin; Ritonavir; RNA, Viral; SARS-CoV-2

As the coronavirus disease 19 (COVID-19) global pandemic rages across the globe, the race to prevent and treat this deadly disease has led to the "off-label" repurposing of drugs such as hydroxychloroquine and lopinavir/ritonavir, which have the potential for unwanted QT-interval prolongation and a risk of drug-induced sudden cardiac death. With the possibility that a considerable proportion of the world's population soon could receive COVID-19 pharmacotherapies with torsadogenic potential for therapy or postexposure prophylaxis, this document serves to help health care professionals mitigate the risk of drug-induced ventricular arrhythmias while minimizing risk of COVID-19 exposure to personnel and conserving the limited supply of personal protective equipment.

Topics: Anti-Infective Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Death, Sudden, Cardiac; Drug Combinations; Drug Monitoring; Drug Repositioning; Electrocardiography; Humans; Hydroxychloroquine; Long QT Syndrome; Lopinavir; Pandemics; Pneumonia, Viral; Risk Adjustment; Ritonavir; SARS-CoV-2; Torsades de Pointes

The novel coronavirus (COVID-19) is currently in epidemic stage. After large-scale interpersonal infection, asymptomatic patients appear. Whether asymptomatic patients are contagious or not and whether they need medication are the arguments among clinical experts.. This paper reports a special asymptomatic couple with COVID-19, of which the male patient is an intercity bus driver but has not induced confirmed infection of his 188 passengers. The patients were treated with four combinations of lopinavir/ritonavir tablets, arbidol tablets, Lianhuaqingwen granules, and recombinant human interferon-α2b (IFN-α2b) injection via aerosol. Their clinical characteristics and medication were summarized and analyzed.. The two asymptomatic patients far away from Wuhan did not seem to be highly contagious. They improved obviously, after treatment with the quadruple therapy, but the effective drug is still unknown. It should be noted that lopinavir/ritonavir tablets have many drug interactions and are the most likely drugs to cause hyperlipidemia and hyperglycemia in these two patients. IFN-α2b is more effective in the early stage of virus infection. Arbidol instruction dose may not be sufficient to inhibit the novel coronavirus

Topics: Asymptomatic Infections; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Female; Humans; Indoles; Interferon alpha-2; Interferon-alpha; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

This is a report of a case with mucous membrane pemphigoid (MMP) with severe eye involvement and concurrent COVID-19 treated successfully using simultaneous high dose intravenous immunoglobulin (IVIg) and anti-viral treatment as hydroxychloroquine, lopinavir/ritonavir, and ribavirin. He had finished a 2-g cycle of rituximab (RTX) in late January. He was receiving mycophenolate mofetil (MMF) for one month and 30 mg prednisolone for three months until his hospitalization. Prednisolone was tapered to 15 mg when current COVID-19 was suspected, considering his recent cough, dyspnea, and fever.

Topics: Adult; Anti-Bacterial Agents; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Deprescriptions; Diabetes Mellitus, Type 2; Drug Combinations; Drug Therapy, Combination; Humans; Hypertension; Immunoglobulins, Intravenous; Immunologic Factors; Iran; Lopinavir; Male; Mycophenolic Acid; Oseltamivir; Pandemics; Pemphigoid, Benign Mucous Membrane; Pneumonia, Viral; Prednisolone; Ritonavir; Rituximab; SARS-CoV-2; Tomography, Spiral Computed

Topics: Adult; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Adult; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Adult; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Adult; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Adult; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Antineoplastic Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Humans; Hydroxychloroquine; Immune Tolerance; Infant; Leukemia, Myeloid, Acute; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

The outbreak of coronavirus disease 2019 (COVID-19) is becoming a global threat. However, our understanding of the clinical characteristics and treatment of critically ill pediatric patients and their ability of transmitting the coronavirus that causes COVID-19 still remains inadequate because only a handful pediatric cases of COVID-19 have been reported.. Epidemiology, clinical characteristics, treatment, laboratory data and follow-up information and the treatment of critically ill infant were recorded.. The infant had life-threatening clinical features including high fever, septic shock, recurrent apnea, petechiae and acute kidney injury and persistent declined CD3+, CD4+ and CD8+ T cells. The duration of nasopharyngeal virus shedding lasted for 49 days even with the administration of lopinavir/ritonavir for 8 days. The CD3+, CD4+ and CD8+ T cells was partially recovered 68 days post onset of the disease. Accumulating of effector memory CD4+ T cells (CD4+TEM) was observed among T-cell compartment. The nucleic acid tests and serum antibody for the severe acute respiratory syndrome coronavirus 2 of the infant's mother who kept intimate contact with the infant were negative despite no strict personal protection.. The persistent reduction of CD4+ and CD8+ T cells was the typical feature of critically ill infant with COVID-19. CD4+ and CD8+ T cells might play a key role in aggravating COVID-19 and predicts a more critical course in children. The prolonged nasopharyngeal virus shedding was related with the severity of respiratory injury. The transmission of SARS-CoV-2 from infant (even very critical cases) to adult might be unlikely.

Topics: Betacoronavirus; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Coronavirus Infections; COVID-19; Critical Illness; Humans; Infant; Lopinavir; Lymphocyte Count; Male; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Virus Shedding

Topics: Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Fatal Outcome; Female; Humans; Lopinavir; Meropenem; Middle Aged; Pandemics; Pneumonia, Viral; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Ritonavir; SARS-CoV-2; Teicoplanin

Topics: Antirheumatic Agents; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Cytochrome P-450 CYP3A Inhibitors; Drug Synergism; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; Retinal Diseases; Retinal Pigment Epithelium; Ritonavir; SARS-CoV-2

Although some information on the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a few selected cases has been reported, data on the clinical characteristics and outcomes of patients hospitalized therewith in South Korea are lacking. We conducted a retrospective single-center study of 98 consecutive hospitalized patients with confirmed SARS-CoV-2 infection at Yeungnam University Medical Center in Daegu, South Korea. Sixty patients were women (61.2%), and the mean age was 55.4±17.1 years. Thirteen patients (13.3%) were treated in the intensive care unit (ICU). The mean interval from symptom onset to hospitalization was 7.7±4.5 days. Patients who received ICU care were significantly older and were more likely to have diabetes mellitus. The National Early Warning Score on the day of admission was significantly higher in patients requiring ICU care. Acute respiratory distress syndrome (13/13 patients; 100%), septic shock (9/13; 69.2%), acute cardiac injury (9/13; 69.2%), and acute kidney injury (8/13; 61.5%) were more common in patients who received ICU care. All patients received antibiotic therapy, and most (97/98 patients; 99.0%) received antiviral therapy (lopinavir/ritonavir). Hydroxychloroquine was used in 79 patients (80.6%), and glucocorticoid therapy was used in 18 patients (18.4%). In complete blood counts, lymphopenia was the most common finding (40/98 patients; 40.8%). Levels of all proinflammatory cytokines were significantly higher in ICU patients. As of March 29, 2020, the mortality rate was 5.1%. Here, we report the clinical characteristics and laboratory findings of SARS-CoV-2 patients in South Korea up to March 29, 2020.

Topics: Adult; Aged; Betacoronavirus; Coronavirus Infections; COVID-19; Cytokines; Drug Combinations; Female; Humans; Hydroxychloroquine; Intensive Care Units; Lopinavir; Lymphopenia; Male; Middle Aged; Pandemics; Pneumonia, Viral; Republic of Korea; Retrospective Studies; Ritonavir; SARS-CoV-2

Since the outbreak of COVID-19, chloroquine has been mentioned as a possible treatment. In vitro studies have shown anti-viral activity of chloroquine against SARS-CoV-2. Recently, the Dutch National Institute for Public Health and the Environment published treatment options for antiviral treatment for COVID-19 where chloroquine was suggested as first choice for off-label treatment, beside remdesivir en lopinavir/ritonavir. In this commentary, we provide a background and history of chloroquine, the evidence for antiviral efficacy of chloroquine and the arguments for off-label use of chloroquine in COVID-19.

Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Humans; Lopinavir; Off-Label Use; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Treatment Outcome

Topics: Adaptive Clinical Trials as Topic; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Dexamethasone; Drug Combinations; Drug Repositioning; Humans; Hydroxychloroquine; Lopinavir; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2; Standard of Care; United Kingdom

A high incidence of thrombotic events has been reported in patients with coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We report 3 clinical cases of patients in Italy with COVID-19 who developed abdominal viscera infarction, demonstrated by computed tomography.

Topics: Abdomen; Aged; Anticoagulants; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Heparin, Low-Molecular-Weight; Humans; Hydroxychloroquine; Infarction; Italy; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Thrombosis; Tomography, X-Ray Computed; Viscera

Topics: Aged, 80 and over; Betacoronavirus; Coronavirus Infections; COVID-19; Hong Kong; Humans; Japan; Lopinavir; Male; Pandemics; Pneumonia, Viral; Ribavirin; Ritonavir; SARS-CoV-2; Ships; Travel

This paper is part of Forum COVID-19: Perspectives in the Humanities and Social Sciences. The novel coronavirus (Sars-CoV-2) poses a huge challenge to the world community. Knowledge about the virus and its properties is limited, but there is a great need to base political and medical decisions on scientific knowledge. This situation is leading to a dynamization of research. A prominent example of such a development is SOLIDARITY. The epistemological dimensions of this trial, which is coordinated by the WHO, and the resulting ethical implications are discussed in this article.

Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Betacoronavirus; Bioethical Issues; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; COVID-19; Drug Combinations; Editorial Policies; Humans; Hydroxychloroquine; International Cooperation; Lopinavir; Pandemics; Pneumonia, Viral; Research Design; Ritonavir; SARS-CoV-2; World Health Organization

Topics: Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Spain; Tacrolimus; Transplant Recipients

Topics: Adjuvants, Immunologic; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Interferon beta-1b; Lopinavir; Multiple Sclerosis; Pandemics; Pneumonia, Viral; Ribavirin; Ritonavir; SARS-CoV-2

Topics: Age Factors; Aged; Aged, 80 and over; Antiviral Agents; Azithromycin; Betacoronavirus; Ceftriaxone; Cobicistat; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Darunavir; Drug Therapy, Combination; Female; HIV Protease Inhibitors; Humans; Hydroxychloroquine; Italy; Lopinavir; Male; Methylprednisolone; Middle Aged; Neoplasms; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Adult; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Adult; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Severe acute respiratory syndrome-related coronavirus

Topics: Betacoronavirus; Brain; Coronavirus Infections; COVID-19; Drug Combinations; Humans; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Seizures; Treatment Outcome

At present, there is no definitive antiviral treatment for coronavirus disease 2019 (COVID-19). We describe our early experience with remdesivir in four critically ill COVID-19 patients. Patients received a 200 mg loading dose, followed by 100 mg daily intravenously for up to 10 days. All patients had been previously treated with other antivirals before remdesivir initiation. One patient experienced a torsade de pointes requiring cardiac resuscitation and one died due to multiple organ failure. Three patients showed biochemical signs of liver injury. Lymphocyte count increased in all patients soon after remdesivir initiation. Nasal swab SARS-CoV-2 RNA became negative in three of four patients after 3 days of therapy. We observed an in vivo virological effect of remdesivir in four critically ill, COVID-19 patients, coupled with a significant burden of adverse events. Although limited by the low number of subjects studied, our preliminary experience may be relevant for clinicians treating COVID-19.

Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Betacoronavirus; Chemical and Drug Induced Liver Injury; Convalescence; Coronavirus Infections; COVID-19; Critical Illness; Darunavir; Drug Administration Schedule; Drug Combinations; Fatal Outcome; Humans; Hydroxychloroquine; Lopinavir; Multiple Organ Failure; Pandemics; Pneumonia, Viral; Ritonavir; RNA, Viral; SARS-CoV-2; Torsades de Pointes

Coronavirus disease 2019 (COVID-19) infection has the potential for targeting the central nervous system, and several neurological symptoms have been described in patients with severe respiratory distress. Here, we described the case of a 60-year-old patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but only mild respiratory abnormalities who developed an akinetic mutism attributable to encephalitis. Magnetic resonance imaging was negative, whereas electroencephalography showed generalized theta slowing. Cerebrospinal fluid analyses during the acute stage were negative for SARS-CoV-2, positive for pleocytosis and hyperproteinorrachia, and showed increased interleukin-8 and tumor necrosis factor-α concentrations. Other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of cerebrospinal fluid parameters was observed after high-dose steroid treatment, thus arguing for an inflammatory-mediated brain involvement related to COVID-19. ANN NEUROL 2020;88:423-427.

Topics: Akinetic Mutism; Antiviral Agents; beta 2-Microglobulin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Electroencephalography; Encephalitis; Glucocorticoids; Humans; Hydroxychloroquine; Interleukin-6; Interleukin-8; Lopinavir; Magnetic Resonance Imaging; Male; Methylprednisolone; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Treatment Outcome; Tumor Necrosis Factor-alpha

Topics: Adult; Aged; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytochrome P-450 CYP3A Inhibitors; Female; Humans; Inpatients; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Young Adult

Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Betacoronavirus; Chloroquine; Clinical Decision-Making; Clinical Trials as Topic; Coronavirus Infections; Cost-Benefit Analysis; COVID-19; Drug Combinations; Empiricism; Humans; Hydroxychloroquine; Information Dissemination; Lopinavir; Pandemics; Pneumonia, Viral; Reproducibility of Results; Ritonavir; SARS-CoV-2; Viral Load

The duration of viral shedding is central to the guidance of decisions about isolation precautions and antiviral treatment. However, studies regarding the risk factors associated with prolonged shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the impact of lopinavir/ritonavir (LPV/r) treatment on viral shedding remain scarce.. Data were collected from all SARS-CoV-2 infected patients who were admitted to isolation wards and had reverse transcription PCR conversion at the No. 3 People's Hospital of Hubei province, China, between 31 January and 9 March 2020. We compared clinical characteristics and SARS-CoV-2 RNA shedding between patients initiated with LPV/r treatment and those without. Logistic regression analysis was employed to evaluate the risk factors associated with prolonged viral shedding.. Of 120 patients, the median age was 52 years, 54 (45%) were male and 78 (65%) received LPV/r treatment. The median duration of SARS-CoV-2 RNA detection from symptom onset was 23 days (interquartile range 18-32 days). Older age (OR 1.03, 95% CI 1.00-1.05; p=0.03) and the lack of LPV/r treatment (OR 2.42, 95% CI 1.10-5.36; p=0.029) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. Patients who initiated LPV/r treatment within 10 days from symptom onset, but not initiated from day 11 onwards, had significantly shorter viral shedding duration compared with those without LPV/r treatment (median 19 days. Older age and the lack of LPV/r treatment were independently associated with prolonged SARS-CoV-2 RNA shedding in patients with coronavirus disease 2019 (COVID-19). Earlier administration of LPV/r treatment could shorten viral shedding duration.

Topics: Adult; Age Factors; Aged; Antiviral Agents; Betacoronavirus; Case-Control Studies; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Female; Hospitalization; Humans; Lopinavir; Male; Middle Aged; Pandemics; Pharynx; Pneumonia, Viral; Real-Time Polymerase Chain Reaction; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Ritonavir; RNA, Viral; SARS-CoV-2; Time Factors; Virus Shedding

Topics: Aged; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Disease Progression; Drug Combinations; Female; Hemodynamics; Humans; Hydroxychloroquine; Hypertension; Italy; Lopinavir; Male; Middle Aged; Oxygen; Pandemics; Pneumonia, Viral; Renin-Angiotensin System; Respiratory Insufficiency; Ritonavir; SARS-CoV-2; Treatment Outcome

Topics: Adult; Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Immunosuppressive Agents; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Therapies, Investigational

Topics: Adult; Anti-Infective Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Aged; Betacoronavirus; Coronavirus Infections; COVID-19; Cytochrome P-450 CYP3A Inhibitors; Drug Therapy, Combination; Female; Humans; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

SARS-CoV-2 is a new pandemic influenza caused by a coronavirus which main route of transmission is through exhaled droplets that primarily infect the nose and the nasopharynx. The aim of this paper is to evaluate the effect of acetic acid, the active component of vinegar, as a potential disinfectant agent for upper airways.. Twenty-nine patients were enrolled and divided into two groups: group 1 (14 patients) was composed of patients treated with off-label hydroxychloroquine and lopinavir/ritonavir, whereas group 2 (15 patients) was composed of patients treated with hydroxychloroquine only, combined with the inhalation of acetic acid disinfectant at a 0.34% concentration. A questionnaire-based evaluation of symptoms was performed after 15 days in both groups.. It appears that the number of patients treated with acetic acid (group 2) that experienced improvement in individual symptoms was double that of the other group of patients (group 1), although numbers are too small for robust statistical analysis.. Considering its potential benefits and high availability, acetic acid disinfection appears to be a promising adjunctive therapy in cases of non-severe COVID-19 and deserves further investigation.

Topics: Acetic Acid; Adult; Aged; Aged, 80 and over; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Disinfection; Female; Humans; Hydroxychloroquine; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Adult; Aged; Antitubercular Agents; Antiviral Agents; Azithromycin; Betacoronavirus; Clinical Laboratory Techniques; Cohort Studies; Coinfection; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Testing; Drug Combinations; Emigrants and Immigrants; Female; Humans; Hydroxychloroquine; Lopinavir; Lung; Male; Middle Aged; Mortality; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Monitoring; Heart Conduction System; Humans; Hydroxychloroquine; Hypokalemia; Long QT Syndrome; Lopinavir; Magnesium; Pandemics; Pneumonia, Viral; Potassium; Retrospective Studies; Ritonavir; SARS-CoV-2

Covid-19 infection caused by the novel coronavirus SARS-COV-2 continues to be a major global health challenge. Till date, no drug has been approved for the treatment of this infection. A number of medications have been proposed and there are ongoing clinical trials around the world to find a suitable treatment. A recent randomised control trial compared lopinavir/ritonavir with standard care among 199 patients with severe Covid-19 infection and concluded that there was no significant reduction in mortality rate with lopinavir/ritonavir. However, there are a few important lessons which may be learnt from the study apart from the statistical reduction in mortality rate. There was a numerical reduction in mortality rate, less intensive care unit stay and less complications in the lopinavir-ritonavir group. This article points out some of those important lessons with some suggestions for future clinical trials.

Topics: Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Resistance, Viral; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Lopinavir in combination with ritonavir is approved for the treatment of HIV and has recently been subject to a clinical trial in severe COVID-19.. This evaluation is of LOTUS China (the Lopinavir Trial for Suppression of SARS-Cov-2 in China), which was a randomized trial in hospitalized subjects with COVID-9 in a respiratory sample and pneumonia. As, in severe COVID-19, lopinavir/ritonavir had no beneficial effects but increased gastrointestinal adverse effects, this combination should not be used at this stage of COVID-19.. In my opinion, the rationale for undertaking a trial of lopinavir/ritonavir in COVID-19 was poor. The analysis of a modified intention to treat group analysis in LOTUS China may have introduced bias. After LOTUS China, there is probably no future for lopinavir in the treatment of severe COVID-19, but some clinical trials for prevention or in various stages of COVID-19 have recently started or are ongoing. The major limitation of these trials is that as lopinavir does not inhibit COVID-19, it is unlikely to prevent infection, reduce viral load, or reduce the severity. However, these trials may be worthwhile in finally determining whether lopinavir has any role in preventing or treating COVID-19.

Topics: Antiviral Agents; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Ritonavir; Severity of Illness Index; Treatment Outcome; Viral Load

Lopinavir/ritonavir has modest antiviral activity against severe acute respiratory syndrome coronavirus 2. The aim was to investigate the viral kinetics and factors associated with viral clearance during lopinavir/ritonavir-based combination treatment in non-severe patients.. Sixty-four patients were retrospectively enrolled. Viral RNA was detected by real-time RT-PCR assay from sputum or throat swab samples at different time points. The patterns of viral kinetics were characterized, and factors associated with rapid viral clearance, which was defined as viral RNA undetectable within two weeks, were analyzed using multivariate logistic regression analyses.. All patients achieved viral RNA negativity and were discharged from the hospital. Furthermore, 48 (75%) and 16 (25%) patients achieved rapid and delayed viral clearance, respectively. The lymphocyte counts of rapid viral clearance patients (1.40 [1.20-1.80] × 109/L) were higher, when compared to delayed viral clearance patients (1.00 [0.70-1.47] × 109/L) (p=0.024). The multivariate logistic analysis revealed that high lymphocyte count (≥1.3×109/L) is an independent factor associated with rapid viral clearance (OR=7.62, 95% CI=1.15-50.34, p=0.035).. The viral shedding exhibited different patterns during treatment. Immune insufficiency is responsible for the delayed viral clearance, suggesting that an immunomodulator should be considered to promote viral clearance in patients with low lymphocyte counts.

Topics: Adult; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Feces; Female; Humans; Hypertension; Logistic Models; Lopinavir; Lymphocyte Count; Male; Middle Aged; Odds Ratio; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; RNA, Viral; SARS-CoV-2; Severity of Illness Index; Viral Load

Topics: Adult; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Deception; Drug Combinations; France; Humans; Hydroxychloroquine; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Scholarly Communication

To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing.. All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiologic history of these patients were retrospectively collected and analyzed.. The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 × 10/L and 2 cases (8%) less than 4 × 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 ± 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital.. The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.

Topics: Adolescent; Age Factors; Antiviral Agents; Betacoronavirus; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Child; Child, Preschool; China; Coronavirus Infections; Cough; COVID-19; Female; Fever; Humans; Infant; Lopinavir; Lymphocyte Count; Male; Pandemics; Pneumonia, Viral; Prognosis; Retrospective Studies; Ribavirin; Ritonavir; SARS-CoV-2; Treatment Outcome

Topics: Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Serotonin Syndrome; Severe acute respiratory syndrome-related coronavirus

In spite of many ongoing attempts to repurpose existing antivirals, no drugs have emerged yet with the desirable activity against SARS-CoV-2. Hydroxychloroquine, lopinavir/ritonavir, remdesivir, umifenovir, favipiravir, ribavirin and beta-interferon-1 gave rise to variable but still inconsistent proof of clinical efficacy in the treatment of COVID-19. Pathogenetic studies have shown significant differences between commonly defined viral pneumonia and COVID-19 pulmonary disease. In severe forms, immune/inflammatory alterations reminiscent of disease forms like Macrophage Activation Syndrome (MAS) have been described, and therapeutic options other than anti-infective have been proposed and implemented, such as anti-inflammatory and anticoagulative agents. The thrombotic phenomena described in the pulmonary vascular bed of patients with severe COVID-19 suggest the administration of low-molecular weight heparin (LMWH) as standard measure in hospitalized patients with COVID-19.

Topics: Adenosine Monophosphate; Alanine; Anticoagulants; Antiviral Agents; Biomarkers; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Critical Care; Disease Management; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Embolism; Endothelium, Vascular; Heparin, Low-Molecular-Weight; Humans; Hydroxychloroquine; Interferon beta-1b; Lopinavir; Macrophage Activation; Pandemics; Pneumonia, Viral; Pulmonary Fibrosis; Randomized Controlled Trials as Topic; Ritonavir; Thromboembolism; Thrombophilia; Thrombosis

As in other areas of the health system, COVID-19 has had a dramatic impact on  hospital compounding. This area has faced numerous challenges, including the  shortage of frequent-use products (hydroalcoholic solutions, lopinavir/ritonavir  suspension), the use of new preparations for SARS-CoV-2 (tocilizumab,  remdesivir), or requests from overwhelmed wards unable to assume the safe  preparation of a high volume of medications (intravenous solutions). The  demand for all types of preparations (topic and oral medications, intravenous  solutions) has increased dramatically. This increase has highlighted the shortage of resources allocated to this area, which has made it difficult to meet the high  demand for preparations. In addition, the pandemic has revealed the scarcity of  research on such basic aspects as agent stability and drug compatibility. One of  the most relevant conclusions drawn from the COVID-19 pandemic is that the  basic areas of hospital pharmacy, along with other, must be maintained and  reinforced, as these are the areas that make us essential.. Como todo el sector sanitario, la farmacotecnia hospitalaria ha sufrido el impacto de la pandemia de la COVID-19, enfrentándose a la necesidad de cubrir el  desabastecimiento de productos de uso frecuente (soluciones hidroalcohólicas,  lopinavir/ritonavir suspensión), a nuevas preparaciones surgidas de las nuevas  necesidades provocadas por el SARS-CoV-2 (tocilizumab, remdesivir), o a  peticiones de plantas desbordadas por la carga asistencial, incapaces de asumir  con un mínimo de seguridad la preparación de numerosos medicamentos  (mezclas intravenosas). El incremento de actividad ha sido en todo tipo de  preparados (tópicos, orales y mezclas intravenosas) y ha puesto de manifiesto la escasez de recursos destinados a esta área, que se ha traducido en serios  problemas para afrontar todas las elaboraciones necesarias, así como la falta de  investigación en aspectos tan básicos como la estabilidad o la compatibilidad de  medicamentos. Probablemente, una de las conclusiones más importantes que  podemos extraer tras la COVID-19 es que —sin menospreciar otras áreas de la  farmacia hospitalaria que también deben desarrollarse— debemos mantener y  potenciar las áreas básicas de nuestra profesión. Aquellas que nos hacen imprescindibles.

Topics: Administration, Oral; Antiviral Agents; Betacoronavirus; Blood Component Transfusion; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Disinfection; Drug Administration Routes; Drug Compounding; Drug Interactions; Drug Stability; Equipment Contamination; Excipients; Forecasting; Home Care Services; Humans; Hydroxychloroquine; Infusions, Intravenous; Lopinavir; Pandemics; Personal Protective Equipment; Pharmacy Service, Hospital; Platelet-Rich Plasma; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Solutions

Cao B, Wang Y, Wen D, et al.

Topics: Adult; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

The unprecedented global scale of COVID-19 globally has triggered a race to discover interventions to reduce associated morbidity and mortality and rapid release of research findings prior to any degree of critical review. As with previous novel infection outbreaks, antiretrovirals are just one drug class that has been held up as a potential strategy for prophylaxis and treatment with scant evidence and risk of harm. Here we summarize the evidence for antiretrovirals to treat COVID-19 and, as a drug that has also been studied in HIV, hydroxychloroquine, and flag some of the pitfalls of using therapies that have not been evaluated robustly.

Topics: Anti-Retroviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Drug Repositioning; Humans; Hydroxychloroquine; Lopinavir; Pandemics; Pneumonia, Viral; Research; Ritonavir; SARS-CoV-2; Tenofovir; Time Factors

Topics: Adjuvants, Immunologic; Adult; Aged; Antimalarials; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Female; Humans; Hydroxychloroquine; Interferon beta-1b; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Treatment Outcome

Despite the severity of coronavirus disease 2019 (COVID-19) being more frequently related to acute respiratory distress syndrome and acute cardiac and renal injuries, thromboembolic events have been increasingly reported. We report a unique series of young patients with COVID-19 presenting with cerebral venous system thrombosis. Three patients younger than 41 years of age with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) infection had neurologic findings related to cerebral venous thrombosis. They were admitted during the short period of 10 days between March and April 2020 and were managed in an academic institution in a large city. One patient had thrombosis in both the superficial and deep systems; another had involvement of the straight sinus, vein of Galen, and internal cerebral veins; and a third patient had thrombosis of the deep medullary veins. Two patients presented with hemorrhagic venous infarcts. The median time from COVID-19 symptoms to a thrombotic event was 7 days (range, 2-7 days). One patient was diagnosed with new-onset diabetic ketoacidosis, and another one used oral contraceptive pills. Two patients were managed with both hydroxychloroquine and azithromycin; one was treated with lopinavir-ritonavir. All patients had a fatal outcome. Severe and potentially fatal deep cerebral thrombosis may complicate the initial clinical presentation of COVID-19. We urge awareness of this atypical manifestation.

Topics: Adult; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Female; Humans; Hydroxychloroquine; Intracranial Thrombosis; Male; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Venous Thrombosis; Young Adult

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Betacoronavirus; China; Chloroquine; Coronavirus Infections; COVID-19; Drug Combinations; Drugs, Chinese Herbal; Female; gamma-Globulins; Glucocorticoids; Hospitalization; Humans; Immunologic Factors; Indoles; Interferons; Lopinavir; Male; Middle Aged; Oxygen; Pandemics; Pneumonia, Viral; Respiration, Artificial; Retrospective Studies; Ritonavir; SARS-CoV-2

Topics: Adult; Aged; Aged, 80 and over; Betacoronavirus; Coronavirus Infections; COVID-19; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Drug Therapy, Combination; Female; Humans; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Time Factors; Withholding Treatment; Young Adult

The rapidly enlarging COVID-19 pandemic caused by the novel SARS-corona virus-2 is a global public health emergency of an unprecedented level. Unfortunately no treatment therapy or vaccine is yet available to counter the SARS-CoV-2 infection, which substantiates the need to expand research efforts in this direction. The indispensable function of the main protease in virus replication makes this enzyme a promising target for inhibitors screening and drug discovery to treat novel coronavirus infection. The recently concluded α-ketoamide ligand-bound X-ray crystal structure of SARS-CoV-2 M. For the study, we have targeted the SARS-CoV-2 M. The phylogenetic analysis of the SARS-CoV-2 genome reveals that the virus is closely related to the Bat-SL-CoV and does not exhibit any divergence at the genomic level. Molecular docking studies revealed that among the 77 drugs, screened top ten drugs shows good binding affinities, whereas the top three drugs: Lopinavir-Ritonavir, Tipranavir, and Raltegravir were undergone for molecular dynamics simulation studies for their conformational stability in the active site of the SARS-CoV-2 M. In the present study among the library of FDA approved antiviral drugs, the top three inhibitors Lopinavir-Ritonavir, Tipranavir, and Raltegravir show the best molecular interaction with the main protease of SARS-CoV-2. However, the in-vitro efficacy of the drug molecules screened in this study further needs to be corroborated by carrying out a biochemical and structural investigation.

Topics: Antiviral Agents; Betacoronavirus; Coronavirus 3C Proteases; Coronavirus Infections; COVID-19; Cysteine Endopeptidases; Drug Combinations; Drug Repositioning; Humans; Lopinavir; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Pandemics; Phylogeny; Pneumonia, Viral; Protease Inhibitors; Pyridines; Pyrones; Raltegravir Potassium; Ritonavir; SARS-CoV-2; Sulfonamides; Viral Nonstructural Proteins

There is no identified pharmacological therapy for COVID-19 patients, where potential therapeutic strategies are underway to determine effective therapy under such unprecedented pandemic. Therefore, combination therapies may have the potential of alleviating the patient's outcome. This study aimed at comparing the efficacy of two different combination regimens in improving outcomes of patients infected by novel coronavirus (COVID-19).. This is a single centered, retrospective, observational study of 60 laboratory-confirmed COVID-19 positive inpatients (≥18 years old) at two wards of the Baqiyatallah Hospital, Tehran, Iran. Patient's data including clinical and laboratory parameters were recorded. According to the drug regimen, the patients were divided into two groups; group I who received regimen I consisting azithromycin, prednisolone, naproxen, and lopinavir/ritonavir and group II who received regimen II including meropenem, levofloxacin, vancomycin, hydroxychloroquine, and oseltamivir.. The oxygen saturation (SpO2) and temperature were positively changed in patients receiving regimen I compared to regimen II (P = 0.013 and P = 0.012, respectively). The serum level of C-reactive protein (CRP) changed positively in group I (P < 0.001). Although there was a significant difference in platelets between both groups (75.44 vs 51.62, P < 0.001), their change did not clinically differ between two groups. The findings indicated a significant difference of the average length of stay in hospitals (ALOS) between two groups, where the patients under regimen I showed a shorter ALOS (6.97 vs 9.93, P = 0.001).. This study revealed the beneficial effect of the short-term use of low-dose prednisolone in combination with azithromycin, naproxen and lopinavir/ritonavir (regimen I), in decreasing ALOS compared to regimen II. Since there is still lack of evidence for safety of this regimen, further investigation in our ongoing follow-up to deal with COVID-19 pneumonia is underway. Graphical abstract.

Topics: Adult; Aged; Azithromycin; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Therapy, Combination; Female; Hospitalization; Humans; Hydroxychloroquine; Iran; Length of Stay; Levofloxacin; Lopinavir; Male; Meropenem; Middle Aged; Naproxen; Oseltamivir; Pneumonia, Viral; Prednisolone; Retrospective Studies; Ritonavir; Treatment Outcome; Vancomycin

Topics: Anti-Anxiety Agents; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Antiviral Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Betacoronavirus; Central Nervous System Stimulants; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme System; Drug Combinations; Drug Interactions; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Psychotropic Drugs; Ritonavir; SARS-CoV-2

Topics: Aged; Anemia; Anticoagulants; Anticonvulsants; Antiviral Agents; Betacoronavirus; Calcium Channel Blockers; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Enzyme Inhibitors; Humans; Hydroxychloroquine; Lopinavir; Lymphopenia; Male; Pandemics; Pneumonia, Viral; Posterior Leukoencephalopathy Syndrome; Ritonavir; SARS-CoV-2; Status Epilepticus; Verapamil

COVID-19 is an ongoing, global public health crisis for which safe and effective treatments need to be identified. The benefit-risk balance for the use of lopinavir-ritonavir in COVID-19 needs to be monitored on an ongoing basis, therefore a systematic benefit-risk assessment was designed and conducted. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation; although initially this evaluation is likely to contain limited information, it is required because of the urgent unmet public need. Importantly, it allows additional data to be incorporated as they become available, and re-evaluation of the benefit-risk profile.. A systematic benefit-risk assessment was conducted using the Benefit-Risk Action Team (BRAT) framework. The exposure of interest was lopinavir-ritonavir treatment in severe COVID-19 compared to standard of care, placebo or other treatments. A literature search was conducted in PubMed and Embase to identify peer-reviewed papers reporting clinical outcomes. Two clinicians constructed a value tree and ranked key benefits and risks in order of considered clinical importance.. We screened 143 papers from PubMed and 264 papers from Embase for lopinavir-ritonavir; seven papers were included in the final benefit-risk assessment. In comparison to standard of care, data for several key benefits and risks were identified for lopinavir-ritonavir. Time to clinical improvement was not significantly different for lopinavir-ritonavir in comparison to standard of care (hazard ratio 1.31, 95% confidence interval 0.95-1.80). From one study, there were fewer cases of acute respiratory distress syndrome with lopinavir-ritonavir compared with standard of care (13% vs 27%). There also appeared to be fewer serious adverse events with lopinavir-ritonavir (20%) vs standard of care (32%). Limited data were available for comparison of lopinavir-ritonavir to other treatments.. Based on currently available data, there was no clear benefit for the use of lopinavir-ritonavir compared to standard of care in severe COVID-19. Risk data suggested a possible decrease in serious adverse events. There was a reduction in acute respiratory distress syndrome with lopinavir-ritonavir in one study. Overall, the benefit-risk profile for lopinavir-ritonavir in severe COVID-19 cannot be considered positive until further efficacy and effectiveness data become available.

Topics: Adult; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Risk Assessment; Ritonavir; SARS-CoV-2

The presence of rhabdomyolysis secondary to multiple infections has been reported, predominantly viral, but also bacterial and fungal. It is well known that COVID-19 can present a wide variety of complications during the course of infection; however, the presence of rhabdomyolysis as an initial condition has not been reported so far. We report a case of rhabdomyolysis as an initial presentation in a patient diagnosed with SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection.

Topics: Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Anticoagulants; Azithromycin; Betacoronavirus; Bicarbonates; Ceftriaxone; Coronavirus Infections; COVID-19; Cytochrome P-450 CYP3A Inhibitors; Enoxaparin; Enzyme Inhibitors; Fluid Therapy; Humans; Hydroxychloroquine; Lopinavir; Lung; Male; Pandemics; Pneumonia, Viral; Respiration, Artificial; Rhabdomyolysis; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome

Topics: Adenine; Adult; Alanine; Anti-HIV Agents; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Dideoxynucleosides; Drug Combinations; Emtricitabine; Female; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, 4 or More Rings; HIV Infections; Humans; Lamivudine; Lopinavir; Male; Middle Aged; Oxazines; Pandemics; Piperazines; Pneumonia, Viral; Pyridones; Ritonavir; SARS-CoV-2; Tenofovir; Transgender Persons

Topics: Adult; Betacoronavirus; Biomarkers; C-Reactive Protein; Coronavirus Infections; COVID-19; Drug Combinations; Female; Humans; Hydroxychloroquine; Imatinib Mesylate; Lopinavir; Lung; Pandemics; Pneumonia, Viral; Protein Kinase Inhibitors; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome

Topics: Adult; Aged; Antirheumatic Agents; Antiviral Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Azithromycin; Betacoronavirus; Cohort Studies; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Female; Glucocorticoids; Humans; Hydroxychloroquine; Immunoglobulins, Intravenous; Immunologic Factors; Lopinavir; Lupus Erythematosus, Systemic; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; Rheumatic Diseases; Ritonavir; SARS-CoV-2; Severity of Illness Index; Spondylarthropathies

Topics: Amides; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Antiviral Agents; Betacoronavirus; Chemical and Drug Induced Liver Injury; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytochrome P-450 Enzyme System; Drug Combinations; Drug Interactions; Histone Deacetylase Inhibitors; Humans; Hydroxychloroquine; Immunosuppression Therapy; Kidney Diseases; Long QT Syndrome; Lopinavir; Neoplasms; Pandemics; Pneumonia, Viral; Poly(ADP-ribose) Polymerase Inhibitors; Proteasome Inhibitors; Protein Kinase Inhibitors; Pyrazines; Ritonavir; SARS-CoV-2

The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic, but the factors influencing viral RNA shedding, which would help inform optimal control strategies, remain unclear.. The clinical course and viral RNA shedding pattern of 267 consecutive symptomatic COVID-19 patients admitted to the hospital from January 20, 2020 to March 15, 2020 were evaluated retrospectively.. The median duration of viral RNA shedding was 12 days (interquartile range 8-16 days) after the onset of illness. Of the 267 patients included in this study, 65.2% had viral RNA clearance within 14 days, 88.8% within 21 days, and 94.4% within 28 days. Older age (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.98-1.00; p = 0.04), time lag from illness onset to hospital admission (HR 0.91, 95% CI 0.88-0.94; p < 0.001), diarrhea (HR 0.59, 95% CI 0.36-0.96; p = 0.036), corticosteroid treatment (HR 0.60, 95% CI 0.39-0.94; p = 0.024), and lopinavir/ritonavir use (HR 0.70, 95% CI 0.52-0.94; p = 0.014) were significantly and independently associated with prolonged viral RNA shedding.. Early detection and timely hospital admission may be warranted for symptomatic COVID-19 patients, especially for older patients and patients with diarrhea. Corticosteroid treatment is associated with prolonged viral RNA shedding and should be used with caution. Lopinavir/ritonavir use may be associated with prolonged viral RNA shedding in non-severe patients; further randomized controlled trials are needed to confirm this finding.

Topics: Adult; Aged; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Hospitalization; Humans; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; RNA, Viral; SARS-CoV-2; Virus Shedding

Coronavirus disease 2019 (COVID-19) is rapidly spreading around the world, causing much morbidity and mortality everywhere. However, effective treatments or vaccines are still not available. Although convalescent plasma (CP) therapy can be useful in the treatment of COVID-19, it has not been widely used in Korea because of the concerns about adverse effects and the difficulty in matching patients to donors. The use of ABO-incompatible plasma is not contraindicated in treatment, but can be hesitated due to the lack of experience of physicians. Here, we describe a 68-year old man with COVID-19 who was treated ABO-incompatible plasma therapy; additionally, we comment on the acute side effects associated with ABO mismatch transfusion. To overcome the obstacles of donor-recipient connections (schedule and distance), we propose the storage of frozen plasma, modification of the current Blood Management Law, and the establishment of a CP bank. We suggest that experience gained in CP therapy will be useful for not only the treatment of COVID-19, but also for coping with new emerging infectious diseases.

Topics: Aged; Antibodies, Neutralizing; Antiviral Agents; Betacoronavirus; Blood Grouping and Crossmatching; Coronavirus Infections; COVID-19; COVID-19 Serotherapy; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Lopinavir; Male; Pandemics; Pneumonia, Viral; Republic of Korea; Ritonavir; SARS-CoV-2; Transfusion-Related Acute Lung Injury

Coronavirus disease 2019 (COVID-19) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the levels of the acute-phase inflammation marker C-reactive protein (CRP). LPV plasma concentrations in 92 patients hospitalized at our institution were prospectively collected. Lopinavir-ritonavir was administered every 12 hours, 800/200 mg on day 1 and 400/100 mg on day 2 until day 5 or 7. HCQ was given at 800 mg, followed by 400 mg after 6, 24, and 48 h. Hematological, liver, kidney, and inflammation laboratory values were analyzed on the day of drug level determination. The median age of study participants was 59 (range, 24 to 85) years, and 71% were male. The median durations from symptom onset to hospitalization and treatment initiation were 7 days (interquartile range [IQR], 4 to 10) and 8 days (IQR, 5 to 10), respectively. The median LPV trough concentration on day 3 of treatment was 26.5 μg/ml (IQR, 18.9 to 31.5). LPV plasma concentrations positively correlated with CRP values (

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Biomarkers; C-Reactive Protein; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Drug Administration Schedule; Drug Combinations; Female; Hospitals, University; Humans; Hydroxychloroquine; Length of Stay; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; SARS-CoV-2; Severity of Illness Index; Survival Analysis

A patient with COVID-19-related severe respiratory failure, with insufficient response to an antiretroviral therapy, hydroxychloroquine and Interleukin-6 (IL-6) antagonist therapy, presented a prompt resolution of the respiratory function and improvement in the radiological picture after baricitinib at an oral dose of 4 mg per day for 2 weeks.

Topics: Acute Disease; Aged; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azetidines; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Drug Repositioning; Humans; Hydroxychloroquine; Lopinavir; Male; Pandemics; Pneumonia, Viral; Purines; Pyrazoles; Respiratory Insufficiency; Ritonavir; SARS-CoV-2; Sulfonamides; Treatment Outcome

At the end of December 2019, the Health Commission of the city of Wuhan, China, alerted the World Health Organization (WHO) to a pneumonia cluster in the city. The cause was identified as being a new virus, later named SARS-CoV-2. We can distinguish three clinical phases of the disease with a distinct pathogenesis, manifestations and prognosis. Here, we describe the case of a 45-year-old male, successfully treated for Coronavirus disease (COVID-19). The patient was feeling sick in early April 2020; he had a fever and pharyngodynia. When he came to our COVID hospital, his breathing was normal. The nasopharyngeal swab specimen turned out positive. High-resolution computed tomography (HRCT) showed mild interstitial pneumonia. The patient was admitted to our department and treated with hydroxychloroquine, ritonavir, darunavir, azithromycin and enoxaparin. On day seven of the disease, the patient's respiratory condition got worse as he was developing acute respiratory distress syndrome (ARDS). He was given tocilizumab and corticosteroids and was immediately treated with non-invasive mechanical ventilation (NIMV). His condition improved, and in the ensuing days, the treatment gradually switched to a high-flow nasal cannula (HFNC); after 18 days, the patient's clinical condition was good.The successful results we have been able to obtain are closely associated with avoidance of invasive ventilation that may lead to intensive care unit (ICU)-related superinfections. In our opinion, it is fundamental to understand that COVID-19 is a systemic disease that is a consequence of an overwhelming inflammatory response, which can cause severe medical conditions, even in young patients.

Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal, Humanized; Azithromycin; China; Coronavirus Infections; COVID-19; Darunavir; Disease Progression; Enoxaparin; Humans; Hydroxychloroquine; Male; Middle Aged; Noninvasive Ventilation; Pandemics; Pneumonia, Viral; Respiratory Distress Syndrome; Ritonavir

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients.. The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7.. Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7.. In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.

Topics: Aged; Coronavirus Infections; COVID-19; Critical Illness; Drug Combinations; Female; Humans; Hydroxychloroquine; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; Standard of Care; Treatment Outcome

Topics: Anticonvulsants; Antiviral Agents; Atazanavir Sulfate; Betacoronavirus; Carbamazepine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Interactions; Humans; Lopinavir; Pandemics; Phenytoin; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Seizures

In view of this pandemic, as of February 2020, South Korea has the second highest number of confirmed cases in the world. Herein, we report four confirmed coronavirus disease 2019 (COVID-19) cases in the early stage of the pandemic in South Korea and describe the identification, diagnosis, clinical course, and management, including one patient's initial mild symptoms at presentation and their progression to pneumonia on day 21 of illness. Within 48 hours of hospitalization, all four patients underwent evaluation for initial laboratory parameters, COVID-19 polymerase chain reaction (PCR), and chest computed tomography (CT) findings. All four mild COVID-19 patients were discharged, and they were re-examined 14 days after discharge. Despite all four of them being asymptomatic, one patient was re-admitted after confirmation of COVID-19 through PCR viral nucleic acid detection. She could be discharged after 7 days with two subsequent negative COVID-19 PCR at 24-hour intervals. Patients with mild COVID-19 generally have normal follow-up chest CT scans after discharge, even if the early chest CT definitely indicates pneumonia. Re-hospitalized patients with COVID-19 PCR positive results after discharge were not related to her initial chest CT, lab, symptoms compared other three patients.

Topics: Adult; Coronavirus Infections; COVID-19; Drug Combinations; Female; Humans; Lopinavir; Male; Pandemics; Pneumonia, Viral; Radiography, Thoracic; Ritonavir

Topics: Acquired Immunodeficiency Syndrome; Adult; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Indoles; Interferon-alpha; Lopinavir; Lung; Male; Pandemics; Pneumonia, Viral; Radiography, Thoracic; Ritonavir; SARS-CoV-2; Sputum; Tomography, X-Ray Computed; Treatment Outcome

The combination lopinavir/ritonavir is recommended to treat HIV-infected patients at the dose regimen of 400/100 mg q12h, oral route. The usual lopinavir trough plasma concentrations are 3000-8000 ng/mL. A trend towards a 28 day mortality reduction was observed in COVID-19-infected patients treated with lopinavir/ritonavir.. To assess the plasma concentrations of lopinavir and ritonavir in patients with severe COVID-19 infection and receiving lopinavir/ritonavir.. Mechanically ventilated patients with COVID-19 infection included in the French COVID-19 cohort and treated with lopinavir/ritonavir were included. Lopinavir/ritonavir combination was administered using the usual adult HIV dose regimen (400/100 mg q12h, oral solution through a nasogastric tube). A half-dose reduction to 400/100 mg q24h was proposed if lopinavir Ctrough was >8000 ng/mL, the upper limit considered as toxic and reported in HIV-infected patients. Lopinavir and ritonavir pharmacokinetic parameters were determined after an intensive pharmacokinetic analysis. Biological markers of inflammation and liver/kidney function were monitored.. Plasma concentrations of lopinavir and ritonavir were first assessed in eight patients treated with lopinavir/ritonavir. Median (IQR) lopinavir Ctrough reached 27 908 ng/mL (15 928-32 627). After the dose reduction to 400/100 mg q24h, lopinavir/ritonavir pharmacokinetic parameters were assessed in nine patients. Lopinavir Ctrough decreased to 22 974 ng/mL (21 394-32 735).. In mechanically ventilated patients with severe COVID-19 infections, the oral administration of lopinavir/ritonavir elicited plasma exposure of lopinavir more than 6-fold the upper usual expected range. However, it remains difficult to safely recommend its dose reduction without compromising the benefit of the antiviral strategy, and careful pharmacokinetic and toxicity monitoring are needed.

Topics: Administration, Oral; Betacoronavirus; Coronavirus Infections; COVID-19; Cytochrome P-450 CYP3A Inhibitors; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Lopinavir; Male; Middle Aged; Pandemics; Pharmaceutical Solutions; Pneumonia, Viral; Prospective Studies; Respiration, Artificial; Ritonavir; SARS-CoV-2

Interferons (IFNs) are widely used in treating coronavirus disease 2019 (COVID-19) patients. However, a recent report of ACE2, the host factor mediating SARS-Cov-2 infection, identifying it as interferon-stimulated raised considerable safety concern. To examine the association between the use and timing of IFN-α2b and clinical outcomes, we analyzed in a retrospective multicenter cohort study of 446 COVID-19 patients in Hubei, China. Regression models estimated that early administration (≤5 days after admission) of IFN-α2b was associated with reduced in-hospital mortality in comparison with no admission of IFN-α2b, whereas late administration of IFN-α2b was associated with increased mortality. Among survivors, early IFN-α2b was not associated with hospital discharge or computed tomography (CT) scan improvement, whereas late IFN-α2b was associated with delayed recovery. Additionally, early IFN-α2b and umifenovir alone or together were associated with reduced mortality and accelerated recovery in comparison with treatment with lopinavir/ritonavir (LPV/r) alone. We concluded that administration of IFN-α2b during the early stage of COVID-19 could induce favorable clinical responses.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Betacoronavirus; Child; China; Cohort Studies; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Female; Hospital Mortality; Host Microbial Interactions; Humans; Indoles; Interferon alpha-2; Interferon-alpha; Length of Stay; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; SARS-CoV-2; Treatment Outcome; Young Adult

To determine the prevalence of potential interactions in COVID-19 patients receiving lopinavir/ritonavir (LPV/r). The secondary objective was to develop recommendations and identify the risk factors associated with presenting potential interactions with LPV/r.. Cross-sectional and multicenter study with the participation of 2 hospitals. COVID-19 patients over 18 years of age, admitted to hospital and under treatment with LPV/r were included. A screening of potential interactions related to LPV/r and home and hospital medication was carried out. Lexicomp® (Uptodate), HIV-drug interactions and COVID-drug interactions were used as the query database.. 361 patients with a mean age of 62.77 ± 14.64 years were included, where 59.6% (n = 215) were men. 62.3% (n = 225) had 1 or more potential interactions and 26, 87% (n = 97) 2 or more. The independent variables associated with presenting ≥1 potential interactions were age (> 65) (OR 1.95; 95% CI 1.06-3.59, P =.033), ICU admission (OR 9.22; CI 95% 1.98-42.93; P =.005), previous respiratory pathology (OR 2.90; 95% CI 1.15-7.36; P =.024), psychiatric (OR 4.14; 95 CI % 1.36-12.61; P =.013), dyslipidemia (OR 3.21; 95% CI 1.63-6.35; P =.001) and the number of drugs prescribed (OR 4.33; 95% CI 2.40-7.81; P =.000).. The prevalence of potential interactions in COVD-19 patient undergoing treatment with LPV/r is high, with age (> 65), ICU admission, previous respiratory and psychiatric pathology, dyslipidemia and the number of prescribed drugs acting as risk factors.

Topics: Adult; Aged; Aged, 80 and over; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cross-Sectional Studies; Drug Combinations; Drug Interactions; Female; Humans; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Risk Factors; Ritonavir; SARS-CoV-2; Treatment Outcome

Over the month of April, Spain has become the European country with more confirmed cases of COVID-19 infection, after surpassing Italy on April 2nd. The community of Castile and León in Spain is one of the most affected by COVID-19 infection and the province of León has a total of 3711 cases and 425 deaths so far. Rheumatic patients should be given special attention regarding COVID-19 infection due to their immunocompromised state resulting from their underlying immune conditions and use of targeted immune-modulating therapies. Studying epidemiological and clinical characteristics of patients with rheumatic diseases infected with SARS-CoV2 is pivotal to clarify determinants of COVID-19 disease severity in patients with underlying rheumatic disease.. To describe epidemiological characteristics of patients with rheumatic diseases hospitalized with COVID-19 and determine risk factors associated with mortality in a third level Hospital setting in León, Spain.. We performed a prospective observational study, from 1st March 2020 until the 1st of June including adults with rheumatic diseases hospitalized with COVID-19 and performed a univariate and multivariate logistic regression model to estimate ORs and 95% CIs of mortality. Age, sex, comorbidities, rheumatic disease diagnosis and treatment, disease activity prior to infection, radiographic and laboratorial results at arrival were analysed.. During the study period, 3711 patients with COVID-19 were admitted to our hospital, of whom 38 (10%) had a rheumatic or musculoskeletal disease. Fifty-three percent were women, with a mean age at hospital admission of 75.3 (IQR 68-83) years. The median length of stay was 11 days. A total of 10 patients died (26%) during their hospital admission. Patients who died from COVID-19 were older (median age 78.4 IQR 74.5-83.5) than those who survived COVID-19 (median age 75.1 IQR 69.3-75.8) and more likely to have arterial hypertension (9 [90%] vs 14 [50%] patients; OR 9 (95% CI 1.0-80.8), p 0.049), dyslipidaemia (9 (90%) vs 12 (43%); OR 12 (95% CI 1.33-108), p 0.03), diabetes ((9 (90%) vs 6 (28%) patients; OR 33, p 0.002), interstitial lung disease (6 (60%) vs 6 (21%); OR 5.5 (95% CI 1.16-26), p 0.03), cardiovascular disease (8 (80%) vs 11 (39%); OR 6.18 (95% IC 1.10-34.7, p 0.04) and a moderate/high index of rheumatic disease activity (7 (25%) vs 6(60%); OR 41.4 (4.23-405.23), p 0.04). In univariate analyses, we also found that patients who died from COVID-19 had higher hyperinflammation markers than patients who survived: C-reactive protein (181 (IQR 120-220) vs 107.4 (IQR 30-150; p 0.05); lactate dehydrogenase (641.8 (IQR 465.75-853.5) vs 361 (IQR 250-450), p 0.03); serum ferritin (1026 (IQR 228.3-1536.3) vs 861.3 (IQR 389-1490.5), p 0.04); D-dimer (12,019.8 (IQR 843.5-25,790.5) vs 1544.3 (IQR 619-1622), p 0.04). No differences in sex, radiological abnormalities, rheumatological disease, background therapy or symptoms before admission between deceased patients and survivors were found. In the multivariate analysis, the following risk factors were associated with mortality: rheumatic disease activity (p = 0.003), dyslipidaemia (p = 0.01), cardiovascular disease (p = 0.02) and interstitial lung disease (p = 0.02). Age, hypertension and diabetes were significant predictors in univariate but not in multivariate analysis. Rheumatic disease activity was significantly associated with fever (p = 0.05), interstitial lung disease (p = 0.03), cardiovascular disease (p = 0.03) and dyslipidaemia (p = 0.01).. Our results suggest that comorbidities, rheumatic disease activity and laboratorial abnormalities such as C-reactive protein (CRP), D-Dimer, lactate dehydrogenase (LDH), serum ferritin elevation significantly associated with mortality whereas previous use of rheumatic medication did not. Inflammation is closely related to severity of COVID-19. Key Points • Most patients recover from COVID-19. • The use of DMARDs, corticosteroids and biologic agents did not increase the odds of mortality in our study. • Rheumatic disease activity might be associated with mortality.

Topics: Age Factors; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Antiviral Agents; Betacoronavirus; C-Reactive Protein; Cardiovascular Diseases; Comorbidity; Coronavirus Infections; COVID-19; Diabetes Mellitus; Drug Combinations; Dyslipidemias; Female; Ferritins; Fibrin Fibrinogen Degradation Products; Hospitalization; Humans; Hydroxychloroquine; Hypertension; Interleukin 1 Receptor Antagonist Protein; L-Lactate Dehydrogenase; Length of Stay; Lopinavir; Lung Diseases, Interstitial; Male; Mortality; Odds Ratio; Pandemics; Pneumonia, Viral; Prospective Studies; Rheumatic Diseases; Risk Factors; Ritonavir; SARS-CoV-2; Severity of Illness Index; Spain

The COVID-19 pandemic presents two main concerns for patients with myasthenia gravis (MG); chronic immunosuppression may put them at greater risk, and some proposed treatments for COVID-19 could cause MG exacerbation.. We present three patients with generalized seropositive MG who developed COVID-19. All patients had a favorable outcome, with only one patient experiencing exacerbation. In this case, exacerbation began before COVID-19; she required ICU admission, non-invasive ventilatory support, and received hydroxychloroquine, lopinavir and ritonavir which were well tolerated. One patient received IVIG in place of scheduled plasma exchange.. Outcome was favorable in all cases despite immunosuppressive therapy, use of experimental COVID-19 medication and switching of plasma exchange for IVIG.

Topics: Adult; Aged; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Diabetes Mellitus, Type 2; Female; Humans; Hydroxychloroquine; Hypertension; Hypothyroidism; Immunocompromised Host; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lopinavir; Male; Myasthenia Gravis; Pandemics; Plasmapheresis; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Treatment Outcome

The outbreak of COVID-19 posed the issue of urgently identifying treatment strategies. Colchicine was considered for this purpose based on well-recognised anti-inflammatory effects and potential antiviral properties. In the present study, colchicine was proposed to patients with COVID-19, and its effects compared with 'standard-of-care' (SoC).. In the public hospital of Esine, northern Italy, 140 consecutive inpatients, with virologically and radiographically confirmed COVID-19 admitted in the period 5-19 March 2020, were treated with 'SoC' (hydroxychloroquine and/or intravenous dexamethasone; and/or lopinavir/ritonavir). They were compared with 122 consecutive inpatients, admitted between 19 March and 5 April 2020, treated with colchicine (1 mg/day) and SoC (antiviral drugs were stopped before colchicine, due to potential interaction).. This proof-of-concept study may support the rationale of use of colchicine for the treatment of COVID-19. Efficacy and safety must be determined in controlled clinical trials.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents; Antiviral Agents; Betacoronavirus; Case-Control Studies; Cohort Studies; Colchicine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Dexamethasone; Drug Combinations; Enzyme Inhibitors; Female; Hospitalization; Humans; Hydroxychloroquine; Italy; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Proof of Concept Study; Proportional Hazards Models; Respiratory Distress Syndrome; Ritonavir; SARS-CoV-2; Survival Rate

The effectiveness of lopinavir/ritonavir (LPV/r) and chloroquine treatment for COVID-19 has not been verified.. We conducted a retrospective study to summarize the clinical practices of nonsevere patients with COVID-19 receiving the standard care, LPV/r or chloroquine in Beijing Ditan Hospital from January 20 to March 26, 2020. The main outcome measurements include the changes of cycle threshold values of open reading frame 1 ab (ORF1ab) and nucleocapsid (N) genes by reverse transcriptase-polymerase chain reaction assay from day 1 to 7 after admission for patients receiving standard care or after treatment being initiated for patients receiving either LPV/r or chloroquine. The proportion of developing severe illness, fever duration and the time from symptom onset to chest computer tomography improvement, and negative conversion of nucleic acid were compared.. Of the 129 patients included in the study, 59 received the standard care, 51 received LPV/r, and 19 received chloroquine. The demographics and baseline characteristics were comparable among the 3 groups. The median duration of fever, median time from symptom onset to chest computer tomography improvement, and negative conversion of the nucleic acid were similar among the 3 groups. The median increase in cycle threshold values of N and ORF1ab gene for patients receiving LPV/r or chloroquine or the standard care during the treatment course was 7.0 and 8.5, 8.0, and 7.6, 5.0, and 4.0, respectively. These figures were not found significantly different among the 3 groups.. Antiviral therapy using LPV/r or chloroquine seemed not to improve the prognosis or shorten the clinical course of COVID-19.

Topics: Adult; Antimalarials; Chloroquine; Chronic Disease; Coronavirus Infections; COVID-19; Drug Combinations; Female; Fever; HIV Protease Inhibitors; Humans; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; Treatment Outcome; Young Adult

Due to the COVID-19 pandemic caused by infection with the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), transplant medicine also had to face a new, hitherto unknown challenge. To be prepared for any possibility, we consider it important to summarize the current knowledge regarding COVID-19 of liver and kidney transplant patients. Very early reports from Spanish and French registry recorded fatality rates of 18.6% and 13%, respectively, in renal patients which suggests a moderately worse outcome compared to the general population. In patients with positive PCR test but not showing clinical signs, the reduction of immunosuppression is not advised. In the case of gastrointestinal or respiratory signs with fever, the discontinuation of mycophenolate or mTOR inhibitors is recommended with decrease of the trough levels of calcineurin inhibitors to the lowest effective limit. Stop (kidney transplanted patients) or decrease (liver transplanted patients) immunosuppression and maintain corticosteroids when pulmonal injury develops and consider anti-IL1 and anti-IL6 monoclonal antibody use when hyperinflammatory syndrome is evolving. No proven effective treatment for SARS-CoV-2 exists currently. The use of lopinavir/ritonavir should be avoided because of the severe drug interaction with calcineurin inhibitors. The efficacy and tolerability of hidroxychloroquin remains to be also questionable; enroll patients into clinical trial with remdesivir or favipiravir if available. COVID-19 is characterized by virus-induced endothelial dysfunction, procoagulant state and renin-angiotensin-aldosteron system imbalance. Early thromboprofilaxis combination with low-molecular-weight heparin and low-dose aspirin is strongly recommended with the maintenance of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II-receptor blocker (ARB) therapy when they were prescribed earlier. Orv Hetil. 2020; 161(32): 1310-1321.

Topics: Adrenal Cortex Hormones; Betacoronavirus; Calcineurin Inhibitors; Contraindications, Drug; Coronavirus Infections; COVID-19; Drug Combinations; Drug Interactions; Humans; Immunosuppression Therapy; Kidney Transplantation; Liver Transplantation; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Transplant Recipients

Observational case-control study.. Individuals with spinal cord injury (SCI) develop systemic physiological changes that could increase the risk of severe evolution of coronavirus disease 2019 (COVID-19) and result in atypical clinical features of COVID-19 with possible delay in both diagnosis and treatment. We evaluated differences in clinical features and evolution of COVID-19 between people with SCI and able-bodied individuals.. The study was conducted in an Italian inpatient rehabilitation referral center for individuals with SCI during the lockdown for the COVID-19 pandemic.. We compared clinical information between patients with SCI and able-bodied healthcare workers of the same center who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nasopharyngeal swab polymerase chain reaction.. Overall, 15 out of the 25 SCI patients admitted to the center and 17 out of the 69 healthcare workers tested positive for SARS-CoV-2. Patients with SCI exhibited a significantly more advanced age and a higher prevalence of comorbidities. Nevertheless, no significant differences in clinical expression of COVID-19 and treatment strategies were observed between the two groups. All hospitalized subjects were treated in nonintensive care units and no deaths occurred in either group.. This study does not support the supposed notion that COVID-19 could exhibit atypical clinical features or a worse evolution in the frail population of people with SCI.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Anticoagulants; Antiviral Agents; Azithromycin; Betacoronavirus; Case-Control Studies; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Enzyme Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Hydroxychloroquine; Italy; Lopinavir; Male; Middle Aged; Oxygen Inhalation Therapy; Pandemics; Pneumonia, Viral; Prognosis; Rehabilitation Centers; Ritonavir; SARS-CoV-2; Spinal Cord Injuries

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is already responsible for far more deaths than previous pathogenic coronaviruses (CoVs) from 2002 and 2012. The identification of clinically approved drugs to be repurposed to combat 2019 CoV disease (COVID-19) would allow the rapid implementation of potentially life-saving procedures. The major protease (Mpro) of SARS-CoV-2 is considered a promising target, based on previous results from related CoVs with lopinavir (LPV), an HIV protease inhibitor. However, limited evidence exists for other clinically approved antiretroviral protease inhibitors. Extensive use of atazanavir (ATV) as antiretroviral and previous evidence suggesting its bioavailability within the respiratory tract prompted us to study this molecule against SARS-CoV-2. Our results show that ATV docks in the active site of SARS-CoV-2 Mpro with greater strength than LPV, blocking Mpro activity. We confirmed that ATV inhibits SARS-CoV-2 replication, alone or in combination with ritonavir (RTV) in Vero cells and a human pulmonary epithelial cell line. ATV/RTV also impaired virus-induced enhancement of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels. Together, our data strongly suggest that ATV and ATV/RTV should be considered among the candidate repurposed drugs undergoing clinical trials in the fight against COVID-19.

Topics: Animals; Antiviral Agents; Atazanavir Sulfate; Betacoronavirus; Cell Death; Chlorocebus aethiops; Coronavirus 3C Proteases; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cysteine Endopeptidases; Cytokines; Drug Therapy, Combination; Humans; Inflammation; Lopinavir; Molecular Docking Simulation; Monocytes; Pandemics; Pneumonia, Viral; Protease Inhibitors; Ritonavir; SARS-CoV-2; Vero Cells; Viral Nonstructural Proteins; Virus Replication

At the end of 2019, the Novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), spread rapidly from China to the whole world. Circadian rhythms can play crucial role in the complex interplay between viruses and organisms, and temporized schedules (chronotherapy) have been positively tested in several medical diseases. We aimed to compare the possible effects of a morning vs. evening antiviral administration in COVID patients.. We retrospectively evaluated all patients admitted to COVID internal medicine units with confirmed SARS-CoV-2 infection, and treated with darunavir-ritonavir (single daily dose, for seven days). Age, sex, length of stay (LOS), pharmacological treatment, and timing of antiviral administration (morning or evening), were recorded. Outcome indicators were death or LOS, and laboratory parameters, e.g., variations in C-reactive protein (CRP) levels, ratio of arterial oxygen partial pressure (PaO2, mmHg) to fractional inspired oxygen (FiO2) (PaO2/FiO2), and leucocyte count.. The total sample consisted of 151 patients, 33 (21.8%) of whom were selected for antiviral treatment. The mean age was 61.8±18.3 years, 17 (51.5%) were male, and the mean LOS was 13.4±8.6 days. Nine patients (27.3%) had their antiviral administration in the morning, and 24 (72.7%) had antiviral administration in the evening. No fatalities occurred. Despite the extremely limited sample size, morning group subjects showed a significant difference in CRP variation, compared to that in evening group subjects (-65.82±33.26 vs. 83.32±304.89, respectively, p<0.032). No significant differences were found for other parameters.. This report is the first study evaluating temporized morning vs. evening antiviral administration in SARS-CoV-2 patients. The morning regimen was associated with a significant reduction in CRP values. Further confirmations with larger and multicenter samples of patients could reveal novel potentially useful insights.

Topics: Adult; Aged; Aged, 80 and over; Antiviral Agents; Betacoronavirus; Blood Gas Analysis; C-Reactive Protein; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Darunavir; Drug Chronotherapy; Drug Therapy, Combination; Hospital Mortality; Humans; Italy; Length of Stay; Leukocyte Count; Middle Aged; Oxygen; Pandemics; Partial Pressure; Pneumonia, Viral; Retrospective Studies; Ritonavir; SARS-CoV-2

In the last months great efforts have been developed to evaluate the more efficient therapeutic agents in the management of patients with COVID-19. Currently, no specific drug combination has consistently demonstrated an association with mortality. The aim of this study was to assess the pattern of associations observed between the different in-hospital treatments administered to a series of 238 patients admitted for COVID-19 and their relationship with mortality.. The electronic medical records of patients that discharged or died from COVID-19 in the Hospital Universitario San Cecilio (Granada, Spain) between March 16 and April 10, 2020 were analysed. From these records, information was obtained on sex, age, comorbidities at admission, clinical information, analytical parameters, imaging tests and empirical treatments used. The outcome variable was the in-hospital mortality. To estimate the associations between the different therapeutic alternatives and the risk of mortality, hazard ratios adjusted for age, sex, previous pathologies and severity at discharge were estimated using Cox regression models.. The most frequently used combination of drugs was low molecular weight heparins, hydroxychloroquine, and ritonavir/lopinavir. None of the analysed treatments showed independent association with mortality. The drugs that showed a greater inverse association with mortality were tocilizumab and corticoids.. The observed association patterns are consistent with previous literature. It seems necessary to design randomized controlled clinical trials that evaluate the possible protector effect of tocilizumab and corticoids in the risk of mortality for some subgroups of COVID-19 hospitalized patients.

Topics: Adrenal Cortex Hormones; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azithromycin; Betacoronavirus; Comorbidity; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Female; Humans; Hydroxychloroquine; Inpatients; Lopinavir; Male; Pandemics; Pneumonia, Viral; Proportional Hazards Models; Retrospective Studies; Ritonavir; SARS-CoV-2; Spain; Treatment Outcome

Since December 2019, severe acute respiratory syndrome coronavirus 2 infection has spread worldwide. We all are concerned about immunocompromised children, especially hematologic and oncologic pediatric patients. We want to share our experience with 2 pediatric cancer patients with severe acute respiratory syndrome coronavirus 2 infection. Both presented mild disease and good outcome. No respiratory symptoms were identified, but both developed diarrhea, one probably secondary to lopinavir/ritonavir. Pediatric cancer patients may have milder disease than adults, but larger studies are needed to make conclusions.

Topics: Adolescent; Betacoronavirus; Child; Child, Preschool; Coronavirus Infections; COVID-19; Diarrhea; Female; Humans; Kidney Neoplasms; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; Sarcoma, Ewing; SARS-CoV-2; Spain; Wilms Tumor

A 78-year-old man had a medical history of hypertension, atrial fibrillation, chronic kidney disease, and metastatic castration-resistant prostate cancer (CRPC). He had progressed to first-line therapy for CRPC with abiraterone plus androgen-deprivation therapy (ADT) and as second-line therapy he was being treated with docetaxel, with biochemical progression in his last prostate specific antigen measurement. He was admitted to the hospital on April 2020, in the middle of the coronavirus disease 2019 (COVID-19) pandemic, because of painful bone lesions and deterioration of renal function.

Topics: Aged; Androgen Antagonists; Androstenes; Anticoagulants; Antineoplastic Agents; Betacoronavirus; Bone Density Conservation Agents; Bone Neoplasms; Cancer Pain; Coronavirus Infections; COVID-19; Disease Progression; Docetaxel; Drug Combinations; Eligibility Determination; Heparin, Low-Molecular-Weight; Humans; Intensive Care Units; Lopinavir; Male; Oxygen Inhalation Therapy; Palliative Care; Pandemics; Pneumonia, Viral; Prostatic Neoplasms, Castration-Resistant; Renal Insufficiency; Respiratory Insufficiency; Reverse Transcriptase Polymerase Chain Reaction; Ritonavir; SARS-CoV-2; Severity of Illness Index; Zoledronic Acid

Topics: Aged, 80 and over; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Eryptosis; Erythrocytes; Humans; Lopinavir; Lung; Male; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed

To describe clinical characteristics of patients with rheumatic and musculoskeletal diseases (RMDs) and immunosuppressive therapies with Coronavirus disease 2019 (COVID-19) at an academic rheumatology center in Madrid and to identify baseline variables associated with a severe infection requiring hospitalization.. We identified SARS-CoV-2 positive cases by polymerase chain reaction performed at our center within an updated RMDs database in our clinic. Additional RMDs patients were identified when they contacted the clinic because of a positive infection. Data extraction included diagnosis, demographics, immunosuppressive treatment, comorbidities, and laboratory tests. Comparisons between patients with or without hospitalization were performed. Multivariate logistic regression was used to analyze associations between baseline variables and need for hospitalization.. A total of 62 patients with COVID-19 and underlying RMDs were identified by April 24, 2020. Median age was 60.9 years, and 42% men. Forty-two patients required hospitalization; these were more frequently men, older and with comorbidities. There were no statistically significant between-group differences for rheumatologic diagnosis and for baseline use of immunosuppressive therapy except for glucocorticoids that were more frequent in hospitalized patients. Total deaths were 10 (16%) patients. In multivariate analysis, male sex (odds ratio [OR], 8.63; p = 0.018), previous lung disease (OR, 27.47; p = 0.042), and glucocorticoids use (> 5 mg/day) (OR, 9.95; p = 0.019) were significantly associated to hospitalization.. Neither specific RMD diagnoses or exposures to DMARDs were associated with increased odds of hospitalization. Being male, previous lung disease and exposure to glucocorticoids were associated with higher odds of hospitalization in RMDs patients.

Topics: Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Antiviral Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Autoimmune Diseases; Azithromycin; Betacoronavirus; Comorbidity; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Female; Glucocorticoids; Hospitalization; Humans; Hydroxychloroquine; Immunosuppressive Agents; Logistic Models; Lopinavir; Lung Diseases; Lupus Erythematosus, Systemic; Male; Middle Aged; Multivariate Analysis; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; SARS-CoV-2; Severity of Illness Index; Sex Factors; Spain

The impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here, we compare the outcomes of a cohort of patients with rheumatic diseases with a matched control cohort to identify potential risk factors for severe illness.. In this comparative cohort study, we identified hospital PCR+COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or connective tissue diseases (CTDs). Non-rheumatic controls were randomly sampled 1:1 and matched by age, sex and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, intensive care unit admission or serious complications. We assessed the association between the outcome and the potential prognostic variables, adjusted by COVID-19 treatment, using logistic regression.. The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 (IQR 53-78) years and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and CTD (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID-19 was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID-19 were increased age (OR 4.83; 95% CI 2.78 to 8.36), male sex (1.93; CI 1.21 to 3.07) and having a CTD (OR 1.82; CI 1.00 to 3.30).. In hospitalised patients with chronic inflammatory rheumatic diseases, having a CTD but not IA nor previous immunosuppressive therapies was associated with severe COVID-19.

Topics: Adenosine Monophosphate; Age Factors; Aged; Alanine; Antiviral Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Betacoronavirus; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Comorbidity; Connective Tissue Diseases; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Female; Glucocorticoids; Hospitalization; Humans; Hydroxychloroquine; Immunosuppressive Agents; Logistic Models; Lopinavir; Lupus Erythematosus, Systemic; Male; Middle Aged; Obesity; Pandemics; Pneumonia, Viral; Polymyalgia Rheumatica; Prognosis; Rheumatic Diseases; Risk Factors; Ritonavir; SARS-CoV-2; Severity of Illness Index; Sex Factors; Sjogren's Syndrome; Spondylarthropathies

Topics: Age Factors; Aged; Aged, 80 and over; Antiviral Agents; Betacoronavirus; Bradycardia; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Female; Heart Rate; Humans; Intensive Care Units; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prospective Studies; Risk Assessment; Risk Factors; Ritonavir; SARS-CoV-2; Time Factors; Treatment Outcome

Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome.. This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HROW).. Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO2/FiO2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HROW 0.48, 95%CI, 0.23-0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HROW 0.41, 95%CI: 0.19-0.89, p = 0.025.. Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antimalarials; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Darunavir; Female; Follow-Up Studies; HIV Protease Inhibitors; Humans; Hydroxychloroquine; Male; Methylprednisolone; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Treatment Outcome

As the global COVID-19 pandemic continues, unabated and clinical trials demonstrate limited effective pharmaceutical interventions, there is a pressing need to accelerate treatment evaluations. Among options for accelerated development is the evaluation of drug combinations in the absence of prior monotherapy data. This approach is appealing for a number of reasons. First, combining two or more drugs with related or complementary therapeutic effects permits a multipronged approach addressing the variable pathways of the disease. Second, if an individual component of a combination offers a therapeutic effect, then in the absence of antagonism, a trial of combination therapy should still detect individual efficacy. Third, this strategy is time saving. Rather than taking a stepwise approach to evaluating monotherapies, this strategy begins with testing all relevant therapeutic options. Finally, given the severity of the current pandemic and the absence of treatment options, the likelihood of detecting a treatment effect with combination therapy maintains scientific enthusiasm for evaluating repurposed treatments. Antiviral combination selection can be facilitated by insights regarding SARS-CoV-2 pathophysiology and cell cycle dynamics, supported by infectious disease and clinical pharmacology expert advice. We describe a clinical evaluation strategy using adaptive combination platform trials to rapidly test combination therapies to treat COVID-19.

Topics: Antiviral Agents; Betacoronavirus; Clinical Trials as Topic; Coronavirus Infections; COVID-19; Drug Combinations; Drug Repositioning; Drug Therapy, Combination; Epidemiologic Research Design; Humans; Interferon beta-1b; Lopinavir; Pandemics; Pneumonia, Viral; Ribavirin; Ritonavir; SARS-CoV-2

Topics: Acute Kidney Injury; Adult; Antiviral Agents; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Darunavir; Drug Interactions; Drug Monitoring; Humans; Hydroxychloroquine; Immunosuppressive Agents; Liver Transplantation; Male; Pandemics; Pneumonia, Viral; Prednisone; Risk Adjustment; Ritonavir; SARS-CoV-2; Tacrolimus; Transplant Recipients; Treatment Outcome

At the end of February, the Lombardy region (Northern Italy) was involved in the pandemic spread of the new COVID-19. We here summarize the clinical and radiological characteristics of 90 confirmed cases and analyze their role in predicting the evolution of fibrosis.. We retrospectively analyzed the clinical and radiological data of 90 patients with COVID-19 pneumonitis. All subjects underwent an HRCT study on the day of admission and eight weeks later, and were treated with lopinavir + ritonavir (Kaletra) 400/100 mg two times a day or darunavir + ritonavir two times a day, and Hydroxychloroquine 200 mg two times a day. Pulmonary fibrosis was defined according to the Fleischner Society glossary of terms for thoracic imaging.. Twenty-three patients developed pulmonary fibrosis (25.5%): 15 were males, whose mean age was 75 ± 15. The majority were active smokers (60.8%) and had comorbidities (78.2%), above all, hypertension (47.8%), and diabetes (34.7%). Interestingly, in our series of cases, the "reversed halo sign" is frequent (63%) and seems to be a typical COVID-19 pneumonitis pattern. The patients showing fibrosis had a higher grade of systemic inflammation (ESR and PCR) and appeared to have bone marrow inhibition with a significant reduction in platelets, leukocytes, and hemoglobin.. To conclude, our data showed that the reversed halo sign associated with a ground-glass pattern may be a typical HRCT pattern of COVID-19 pneumonitis. The evolution to pulmonary fibrosis is frequent in older males and patients with comorbidities and bone marrow involvement.

Topics: Aged; Aged, 80 and over; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Female; Humans; Hydroxychloroquine; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Pulmonary Fibrosis; Radiography; Retrospective Studies; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed

Fulminant (life-threatening) COVID-19 can be associated with acute respiratory failure (ARF), multi-system organ failure and cytokine release syndrome (CRS). We present a rare case of fulminant COVID-19 associated with reverse-takotsubo-cardiomyopathy (RTCC) that improved with therapeutic plasma exchange (TPE).. A 40 year old previous healthy male presented in the emergency room with 4 days of dry cough, chest pain, myalgias and fatigue. He progressed to ARF requiring high-flow-nasal-cannula (flow: 60 L/minute, fraction of inspired oxygen: 40%). Real-Time-Polymerase-Chain-Reaction (RT-PCR) assay confirmed COVID-19 and chest X-ray showed interstitial infiltrates. Biochemistry suggested CRS: increased C-reactive protein, lactate dehydrogenase, ferritin and interleukin-6. Renal function was normal but lactate levels were elevated. Electrocardiogram demonstrated non-specific changes and troponin-I levels were slightly elevated. Echocardiography revealed left ventricular (LV) basal and midventricular akinesia with apex sparing (LV ejection fraction: 30%) and depressed cardiac output (2.8 L/min) consistent with a rare variant of stress-related cardiomyopathy: RTCC. His ratio of partial arterial pressure of oxygen to fractional inspired concentration of oxygen was < 120. He was admitted to the intensive care unit (ICU) for mechanical ventilation and vasopressors, plus antivirals (lopinavir/ritonavir), and prophylactic anticoagulation. Infusion of milrinone failed to improve his cardiogenic shock (day-1). Thus, rescue TPE was performed using the Spectra Optia™ Apheresis System equipped with the Depuro D2000 Adsorption Cartridge (Terumo BCT Inc., USA) without protective antibodies. Over 5 days he received daily TPE (each lasting 4 hours). His lactate levels, oxygenation, and LV function normalized and he was weaned off vasopressors. His inflammation markers improved, and he was extubated on day-7. RT-PCR was negative on day-17. He was discharged to home isolation in good condition.. Stress-cardiomyopathy may complicate the course of fulminant COVID-19 with associated CRS. If inotropic therapy fails, TPE without protective antibodies may help rescue the critically ill patient.

Topics: Adult; Antiviral Agents; Betacoronavirus; Cardiotonic Agents; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytokine Release Syndrome; Drug Combinations; Echocardiography; Humans; Lopinavir; Male; Pandemics; Plasma Exchange; Pneumonia, Viral; Respiration, Artificial; Respiratory Distress Syndrome; Ritonavir; SARS-CoV-2; Shock, Cardiogenic; Takotsubo Cardiomyopathy

This longitudinal, prospective cohort study aimed to assess risk of QTc interval prolongation and its predicting factors in subjects treated with combinations containing hydroxychloroquine (HCQ) for COVID-19. Moderate-to-severe QTc prolongation during therapy was defined as a QTc interval >470 ms in men or >480 ms in women. Patients were treated under strict cardiac supervision. A total of 105 adults were included [56% male; median (IQR) age 69 (57-79) years]. All patients received therapy with HCQ in combination with azithromycin (AZM), and 95 (90%) also with lopinavir/ritonavir (LPV/r). Concomitant medications classified as having risk of developing torsades de pointes (TdP) were simultaneously used in 81 patients (77%). Moderate-to-severe QTc prolongation was observed in 14 patients (13%), mostly at Days 3-5 from baseline, with 6 (6%) developing severe prolongation (>500 ms). There was no evidence of TdP arrhythmia or TdP-associated death. Adding LPV/r to HCQ+AZM did not significantly prolong the QTc interval. Multivariable Cox regression revealed that comedications with known risk of TdP (HR = 11.28, 95% CI 1.08-117.41), higher neutrophil-to-lymphocyte (NLR) ratio (HR = 1.10, 95% CI 1.03-1.18 per unit increase) and higher serum hs-cardiac troponin I (HR = 4.09, 95% CI 1.36-12.2 per unit increase) were major contributors to moderate-to-severe QTc prolongation. In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed during pharmacological therapy containing HCQ for COVID-19. Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher NLR, are conditions requiring careful QTc interval monitoring.

Topics: Aged; Anti-Infective Agents; Azithromycin; Betacoronavirus; Biomarkers; Coronavirus Infections; COVID-19; Disease Progression; Drug Combinations; Female; Humans; Hydroxychloroquine; Intensive Care Units; Long QT Syndrome; Lopinavir; Lymphocytes; Male; Middle Aged; Neutrophils; Pandemics; Pneumonia, Viral; Prognosis; Proportional Hazards Models; Retrospective Studies; Ritonavir; SARS-CoV-2; Treatment Outcome; Troponin I

We investigated the potential hepatotoxicity of lopinavir/ritonavir recently used in the treatment of Severe Acute Respiratory Syndrome Coronavirus.. This is a retrospective cohort of critical patients in a teaching hospital: 12 treated with lopinavir/ritonavir and 30 in the standard-of-care group.. Elevation occurred more frequently in patients treated with lopinavir/ritonavir (33% vs 6.7%).. Caution is advised regarding the use of lopinavir/ritonavir in the most severe cases of Severe Acute Respiratory Syndrome Coronavirus.

Topics: Aged; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Intensive Care Units; Jaundice; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prospective Studies; Retrospective Studies; Ritonavir; SARS-CoV-2; Severity of Illness Index; Standard of Care

Several drug candidates have been proposed and tested as the latest clinical treatment for coronavirus pneumonia (COVID-19). Chloroquine, hydroxychloroquine, ritonavir/lopinavir, and favipiravir are under trials for the treatment of this disease. The hyperpolarization technique has the ability to further provide a better understanding of the roles of these drugs at the molecular scale and in different applications in the field of nuclear magnetic resonance/magnetic resonance imaging. This technique may provide new opportunities in diagnosis and research of COVID-19. Signal amplification by reversible exchange-based hyperpolarization studies on large-sized drug candidates were carried out. We observed hyperpolarized proton signals from whole structures, due to the unprecedented long-distance polarization transfer by para-hydrogen. We also found that the optimal magnetic field for the maximum polarization transfer yield was dependent on the molecular structure. We can expect further research on the hyperpolarization of other important large molecules, isotope labeling, as well as polarization transfer on nuclei with a long spin relaxation time. A clinical perspective of these features on drug molecules can broaden the application of hyperpolarization techniques for therapeutic studies.

Topics: Amides; Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Drug Discovery; Humans; Lopinavir; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; SARS-CoV-2

Topics: Aged; Anaplastic Lymphoma Kinase; Anti-HIV Agents; Betacoronavirus; Carbazoles; Carcinoma, Non-Small-Cell Lung; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Humans; Hydroxychloroquine; Lopinavir; Lung; Lung Neoplasms; Male; Masks; Noninvasive Ventilation; Pandemics; Piperidines; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome

The clinical manifestations of the SARS-CoV-2 infection are mainly respiratory but the virus can cause a variety of symptoms. Dermatological findings are less well-characterized. Data is scarce on their timing, type and correlation with the immune response.. We present the case of SARS-CoV-2 infection in a previously healthy woman who presented with respiratory symptoms and developed anosmia, diarrhea, and an erythematous maculo-papular rash on day 15 from symptom onset.. The nasopharyngeal swab tested by real time PCR for COVID-19 was positive. We interpreted this as a viral exanthema likely caused by an immune response to SARS-CoV-2 nucleotides.. She was treated with Hydroxychloroquine, Azithromycin and Lopinavir/Ritonavir, and the rash with topical corticosteroids.. All symptoms resolved except for anosmia which persisted for 6 weeks. At the 4- and 6-weeks follow-up the IgG titers for SARS-CoV-2 were high.. We must consider that SARS-CoV-2 has a multi-organ tropism. In our case, the SARS-CoV-2 infection had lung, nasopharyngeal, neurological, digestive, and skin manifestations. Identifying the different manifestations is useful for understanding the extent of SARS-CoV-2 infection. We not only present a rare manifestation but also suggest that cutaneous manifestations may correlate with immunity.

Topics: Administration, Topical; Adult; Antiviral Agents; Azithromycin; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Drug Combinations; Exanthema; Female; Glucocorticoids; Humans; Hydroxychloroquine; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Symptom Assessment; Treatment Outcome

Topics: Anti-Inflammatory Agents; Antiviral Agents; Benzimidazoles; Betacoronavirus; Betamethasone; Causality; Coronavirus Infections; COVID-19; Drug Eruptions; Drug Therapy, Combination; Humans; Hydroxychloroquine; Lopinavir; Male; Middle Aged; Pandemics; Piperidines; Pneumonia, Viral; Prednisone; Ritonavir; SARS-CoV-2; Skin Diseases, Viral

A 64-year-old woman presented to our emergency department during the outbreak of the covid-19 emergency in Italy with syncope, anosmia, mild dyspnoea and atypical chest and dorsal pain. A chest CT scan showed an acute type B aortic dissection (ATBAD) and bilateral lung involvement with ground-glass opacity, compatible with interstitial pneumonia. Nasopharyngeal swabs resulted positive for SARS-CoV-2. For the persistence of chest pain, despite the analgesic therapy, we decided to treat her with a TEVAR. Patient's chest and back pain resolved during the first few days after the procedure. No surgical or respiratory complications occurred and the patient was discharged 14 days after surgery.. By performing the operation under local anesthesia, it was possible to limit both the staff inside the operatory room and droplet/aerosol release. Since we had to perform the operation in a hemodynamics room, thanks to the limited extension of the endoprosthesis and the good caliber of the right vertebral artery we were able to reduce the risk of spinal cord ischemia despite the lack of a revascularization of the left subclavian artery.. A minimally invasive total endovascular approach allows, through local anesthesia and percutaneous access, to avoid surgical cut down and orotracheal intubation. This, combined with a defined management protocol for infected patients, seems to be a reasonable way to perform endovascular aortic procedures in urgent setting, even in a SARSCoV- 2 positive patient.. COVID-19, Dissection, TEVAR.. Nel marzo 2020 una donna di 64 anni si è presentata presso il nostro pronto soccorso con sincope, anosmia, lieve dispnea e dolore toracico. Riferiva inoltre febbricola nei giorni precedenti, ma al momento del ricovero era apiretica e la sua saturazione di ossigeno in aria ambiente era 93%. Una TC del torace (eseguita per escludere una tromboembolia polmonare) ha evidenziato una dissezione aortica acuta di tipo B e una polmonite interstiziale bilaterale, con successiva positività del tampone naso-faringeo per SARS-CoV-2. La dissezione aortica era estesa longitudinalmente per circa 6 cm, con un tear di entrata situato subito distalmente rispetto all’origine dell’arteria succlavia sinistra. Come per tutte le sindromi aortiche acute, la paziente è stata trasferita in terapia intensiva per monitoraggio invasivo della pressione arteriosa; in questo caso è stata pianificata una stanza singola con isolamento da contatto e per droplets. Secondo il protocollo interno è stata impostata una terapia antivirale ed una profilassi antibiotica ed antitrombotica. La somministrazione di ossigeno a basso flusso attraverso occhialini nasali era sufficiente per mantenere una saturazione > 94%. Una scansione TC dopo 24 ore non ha mostrato cambiamenti nell’estensione della dissezione, ma la paziente continuava a riferire dolore toracico nonostante la terapia analgesica per cui è stato deciso di sottoporla a trattamento chirurgico. In anestesia locale (senza intubazione oro-tracheale e con un anestesista in stand-by fuori dalla stanza) ed utilizzando una sala di emodinamica (per la indisponibilità delle sale operatorie, trasformate in terapia intensiva per i pazienti COVID-19) la lesione è stata esclusa mediante il posizionamento di una endoprotesi toracica con copertura intenzionale dell’origine della succlavia di sinistra senza rivascolarizzazione. L’angiografia finale ha mostrato la completa esclusione della dissezione e l’assenza di endoleak. In base al nostro protocollo infettivologico, per l’intera durata della procedura alla paziente è stata applicata una mascherina chirurgica al fine di limitare la diffusione di droplets e l’ossigenoterapia è stata somministrata tramite occhialini nasali. Il personale presente all’interno della sala di emodinamica è stato ridotto al minimo (tre chirurghi vascolari ed un infermiere di sala operatoria) per abbattere il rischio infettivo e l’impiego di dispositivi di protezione individuale. Oltre alla divisa, al camice piombato ed agli occhi

Topics: Anesthesia, Local; Antibiotic Prophylaxis; Anticoagulants; Antiviral Agents; Aortic Aneurysm, Thoracic; Aortic Dissection; Betacoronavirus; Blood Vessel Prosthesis Implantation; Contraindications, Procedure; Coronavirus Infections; COVID-19; Darunavir; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Endovascular Procedures; Enoxaparin; Female; Humans; Hydroxychloroquine; Infection Control; Infectious Disease Transmission, Patient-to-Professional; Intraoperative Complications; Intubation, Intratracheal; Middle Aged; Nasopharynx; Operating Rooms; Pandemics; Patient Isolation; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Spinal Cord Ischemia; Vertebral Artery

The number of people infected with severe acute respiratory syndrome coronavirus 2 is increasing globally, and some patients have a fatal clinical course. In light of this situation, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic on March 11, 2020. While clinical studies and basic research on a treatment for COVID-19 are ongoing around the world, no treatment has yet been proven to be effective. Several clinical studies have demonstrated the efficacy of chloroquine phosphate and nafamostat mesylate with COVID-19. Here, we report the case of a Japanese patient with COVID-19 with severe respiratory failure who improved following the administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate. Hence, hydroxychloroquine with nafamostat mesylate might be a treatment option for severe COVID-19.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Benzamidines; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Guanidines; Hemodiafiltration; Humans; Hydroxychloroquine; Japan; Lopinavir; Male; Pandemics; Pneumonia, Viral; Respiratory Insufficiency; Ritonavir; SARS-CoV-2; Treatment Outcome

To describe the characteristics of liver damage in severe coronavirus disease 2019 (COVID-19) patients in Sichuan area and the effect of antiviral drugs on liver function.. The clinical data of severe COVID-19 patients admitted to Chengdu Public Health Clinical Medical Center from January 21 to February 24, 2020 were retrospectively collected, including demographic data, clinical manifestations and liver function changes within 1 week after admission to intensive care unit (ICU). The changes of liver function during the course of disease in severe COVID-19 patients were analyzed and summarized, and group analysis was performed.. A total of 30 COVID-19 patients with complete clinical data were enrolled. The incidence of severe COVID-19 in elderly men was higher (60.0%), with median age of 61 (47, 79) years old, and those aged 80 or above accounted for 23.3%. The severe COVID-19 patients mainly presented with respiratory symptoms such as fever (96.7%), cough (80.0%) and dyspnea (66.7%). The alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and prothrombin time (PT) of 30 patients were increased to various degrees within 1 week after ICU admission, and albumin (ALB) was decreased. (1) The patients were divided into two groups according to whether to take lopinavir/ritonavir (kaletra). It was shown that the incidence of liver dysfunction in patients taking kaletra was significantly higher than those who did not take kaletra (7-day abnormal rate of ALT was 54% vs. 33%, the abnormal rate of AST was 38% vs. 33%, the abnormal rate of TBil was 8% vs. 0%), but there were no statistical differences (all P > 0.05). (2) The patients were divided into normal dose group (500 mg, twice a day, n = 19) and reduced dose group (250 mg, twice a day, n = 5) according to the dosage of kaletra. It was shown that patients taking low-dose kaletra had a smaller effect on liver function within 1 week after ICU admission than those receiving normal dosage, and ALB, TBil in the reduced dose group were significantly lower than those in the normal dose group on the 2nd day after ICU admission [ALB (g/L): 33.3±2.0 vs. 37.5±4.0, TBil (μmol/L): 6.3±3.3 vs. 11.3±4.8, both P < 0.05].. Severe COVID-19 patients in Sichuan area suffered obvious liver damage in the early course of the disease and have a slower recovery. It is important to pay attention to avoid using drugs that can aggravate liver damage while treating the disease. If there is no alternative drug, liver protection treatment should be considered appropriately.

Topics: Aged; Aged, 80 and over; Antiviral Agents; China; Coronavirus Infections; COVID-19; Drug Combinations; Humans; Liver Diseases; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; Severity of Illness Index; Treatment Outcome

Topics: Alanine Transaminase; Antiviral Agents; Aspartate Aminotransferases; Betacoronavirus; Chemical and Drug Induced Liver Injury; Chloroquine; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Testing; Diagnosis, Differential; Drug Combinations; Hepatitis, Viral, Human; Humans; Liver; Liver Function Tests; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

Improvement of COVID-19 clinical condition was seen in studies where combination of antiretroviral drugs, lopinavir and ritonavir, as well as immunomodulant antimalaric, chloroquine/hydroxychloroquine together with the macrolide-type antibiotic, azithromycin, was used for patient's treatment. Although these drugs are "old", their pharmacological and toxicological profile in SARS-CoV-2 - infected patients are still unknown. Thus, by using in silico toxicogenomic data-mining approach, we aimed to assess both risks and benefits of the COVID-19 treatment with the most promising candidate drugs combinations: lopinavir/ritonavir and chloroquine/hydroxychloroquine + azithromycin. The Comparative Toxicogenomics Database (CTD; http://CTD.mdibl.org), Cytoscape software (https://cytoscape.org) and ToppGene Suite portal (https://toppgene.cchmc.org) served as a foundation in our research. Our results have demonstrated that lopinavir/ritonavir increased the expression of the genes involved in immune response and lipid metabolism (IL6, ICAM1, CCL2, TNF, APOA1, etc.). Chloroquine/hydroxychloroquine + azithromycin interacted with 6 genes (CCL2, CTSB, CXCL8, IL1B, IL6 and TNF), whereas chloroquine and azithromycin affected two additional genes (BCL2L1 and CYP3A4), which might be a reason behind a greater number of consequential diseases. In contrast to lopinavir/ritonavir, chloroquine/hydroxychloroquine + azithromycin downregulated the expression of TNF and IL6. As expected, inflammation, cardiotoxicity, and dyslipidaemias were revealed as the main risks of lopinavir/ritonavir treatment, while chloroquine/hydroxychloroquine + azithromycin therapy was additionally linked to gastrointestinal and skin diseases. According to our results, these drug combinations should be administrated with caution to patients suffering from cardiovascular problems, autoimmune diseases, or acquired and hereditary lipid disorders.

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Chloroquine; Computer Simulation; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Data Mining; Databases, Genetic; Drug Therapy, Combination; Gene Regulatory Networks; Humans; Hydroxychloroquine; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Toxicogenetics

To characterise current COVID-19-related research activities.. Cross-sectional analysis.. Clinical trials registered with ClinicalTrials.gov testing interventions relevant to COVID-19.. ClinicalTrials.gov was searched for COVID-19 and related terms to identify trials registered between 1 December 2019 and 1 May 2020 that test interventions related to the COVID-19 pandemic.. We classified trials according to intervention type, and report key trial characteristics including recruitment status, location, funder type, target enrolment number, intervention model (single group, randomised or sequential assignment) and projected completion date.. Of the 630 identified clinical trials related to COVID-19, 509 (81%) involved the study of drugs or biological agents. Of these trials of drugs and biologics, 305 (60%) use an open-label design, 43 (8%) are single blinded (participant only) and 161 (32%) are double blinded (participant and investigator). 94 (18%) of the drug/biological trials are non-randomised. Either hydroxychloroquine or chloroquine is administered as part of the study protocol in 152 (30%) of the drug/biological trials. The total planned enrolment for these hydroxychloroquine/chloroquine trials is over 200 000 participants, which represents 65% of the total planned enrolment for all registered trials of drugs or biologics. There are also at least 25 registered trials of azithromycin (n=53), convalescent plasma (n=38), lopinavir/ritonavir (n=30), stem cell treatments (n=29) and tocilizumab (n=25). 142 trials were registered in the first 3 months of 2020, and 488 trials were registered between 1 April and 1 May 2020.. These findings demonstrate a robust research response to the COVID-19 pandemic, though many of the currently planned and ongoing trials focus on a small number of potential therapies, and many also lack essential design features and power necessary to provide accurate treatment effect estimates.

Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Azithromycin; Betacoronavirus; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; Double-Blind Method; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Lopinavir; Pandemics; Pneumonia, Viral; Registries; Ritonavir; SARS-CoV-2; Single-Blind Method; Stem Cell Transplantation

Presentation of a case illustrating the benefits of traditional Chinese medicine (TCM) for treatment of Coronavirus disease 2019 (COVID-19) in critically ill patients.. A 58-year-old woman presented with cough, fever, dizziness, chest tightness, polypnea and poor appetite. She was admitted to Guizhou Provincial People's hospital, and diagnosed with critically ill type of COVID-19 in February 2020. According to the patient's symptoms and signs, the TCM syndrome differentiation was qi deficiency, dampness-stasis and toxin accumulation. Then she received the combined therapy of a modified Chinese herbal formula and Western medicine. During a twelve-day period of treatment, her respiratory distress and appetite quickly improved. Abnormal laboratory indicators were resumed in time and lung lesions in CT scan largely absorbed. No side effects associated with this Chinese herbal formula were found. Before discharge, two consecutive nasopharyngeal swabs were shown to be negative for severe acute respiratory coronavirus 2 (SARS-CoV-2).. Our case report suggests that collaborative treatments with traditional Chinese medicine prove beneficial in the management of COVID-19 in critically ill patients. In order to give optimal care for this COVID-19 crisis for the whole world, Chinese medicine practitioners and Western medical doctors should work together in frontline.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Critical Illness; Drug Combinations; Drugs, Chinese Herbal; Female; Humans; Indoles; Lopinavir; Medicine, Chinese Traditional; Methylprednisolone; Middle Aged; Moxifloxacin; Noninvasive Ventilation; Oxygen Inhalation Therapy; Pandemics; Pneumonia, Viral; Qi; Ritonavir; SARS-CoV-2

A prospective observational study was conducted for assessing the therapeutic efficacy of interferon (IFN)-α2b in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first month after the coronavirus disease 2019 (COVID-19) outbreak began in Cuba. From March 11th to April 14th, 814 patients were confirmed SARS-CoV-2 positive in Cuba. Seven hundred sixty-one (93.4%) were treated with a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular administration of IFN-α2b (Heberon

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Betacoronavirus; Child; Child, Preschool; Chloroquine; Coronavirus Infections; COVID-19; Cuba; Drug Therapy, Combination; Female; Humans; Infant; Interferon alpha-2; Interferon-alpha; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prospective Studies; Ritonavir; SARS-CoV-2; Young Adult

The global pandemic of coronavirus disease 2019 (COVID-19) infection is ongoing and associated with high mortality. The aim of this study was to investigate the efficacy and safety of subcutaneous injection of interferon alpha-2b (IFN alpha-2b) combined with lopinavir/ritonavir (LPV/r) in the treatment of COVID-19 infection, compared with that of using LPV/r alone.. Patients diagnosed with laboratory-confirmed COVID-19 infection in Wuhan Red Cross hospital during the period from January 23, 2020 to March 19, 2020 were included. The length of stay, the time to viral clearance and adverse reactions during hospitalization were compared between patients using oral LPV/r and combined therapy of LPV/r and subcutaneous injection of IFN alpha-2b.. A total of 22 patients were treated with LPV/r alone and 19 with combined therapy with subcutaneous injection of IFN alpha-2b. The average length of hospitalization in the combination group was shorter than that of LPV/r group (16 ± 9.7 vs 23 ± 10.5 days; P = 0.028). Moreover, the days of hospitalization in early intervention group decreased from 25 ± 8.5 days to 10 ± 2.9 days compared with delayed intervention group (P = 0.001). Combined therapy with IFN alpha-2b also significantly reduced the duration of detectable virus in the upper respiratory tract. No patient in each group was transferred to intensive care unit (ICU) or died during the treatment. There was no significant difference in the adverse effect composition between two groups.. Subcutaneous injection of IFN alpha-2b combined with LPV/r shortened the length of hospitalization and accelerated viral clearance in COVID-19 patients, which deserves further investigation in clinical practice.

Topics: Aged; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Female; Humans; Injections, Subcutaneous; Interferon alpha-2; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

We performed molecular dynamics simulation of the dimeric SARS-CoV-2 (severe acute respiratory syndrome corona virus 2) main protease (M

Topics: Betacoronavirus; Binding Sites; Biophysical Phenomena; Catalytic Domain; Computational Biology; Coronavirus 3C Proteases; Coronavirus Infections; COVID-19; Cysteine Endopeptidases; Darunavir; Drug Repositioning; HIV Protease Inhibitors; Humans; Indinavir; Lopinavir; Molecular Dynamics Simulation; Nelfinavir; Pandemics; Pneumonia, Viral; Ritonavir; Saquinavir; SARS-CoV-2; Viral Nonstructural Proteins

During the SARSCoV-2 pandemic many drugs have been used as potential treatments in order to improve the clinical outcome and reduce the mortality. But since it is a currently unknown disease, the evidence about efficacy and safety is built as the drugs are prescribed. In this context, intensive pharmacovigilance allows early detection of adverse events, and thereby infer the safety profile of the indication. We conducted an observational, retrospective, single-center study involving adult patients with severe SARS-CoV-2 infection. All adverse events detected in 23 patients in the Intensive Care Unit between March 15 and June 15, 2020 were registered. We describe type and severity of the adverse events and if treatment suspension was needed. The results show a high rate of adverse events (10/23, 43%) in treatment with lopinavir/ritonavir. In most cases early treatment suspension was required. Even though the limitations of our study derived from the small sample size, these results could help in building evidence about the safety of using lopinavir/ritonavir for severe SARS-CoV-2 infection.. Durante el transcurso de la pandemia causada por el virus SARS-CoV-2 se han utilizado diferentes fármacos como potenciales tratamientos específicos con el objetivo de lograr mejoría clínica y/o disminuir la mortalidad de los afectados, pero al tratarse de una enfermedad hasta ahora desconocida, la evidencia acerca de su seguridad y eficacia se va construyendo a medida que se los prescribe. La farmacovigilancia intensiva en este contexto permite detectar eventos adversos y mediante su reporte y análisis inferir el perfil de seguridad en cada indicación. Se realizó un estudio observacional, retrospectivo, en un único centro, en el cual se relevaron los eventos adversos en 23 pacientes adultos en estado crítico, de los cuales 18 recibieron lopinavir/ritonavir como tratamiento empírico, entre el 15 de marzo y el 15 de junio de 2020, durante su internación en una Unidad de Cuidados Intensivos. Se describe el tipo de eventos adversos, su gravedad y si fueron motivo de suspensión del tratamiento. Los resultados del presente análisis muestran una alta tasa de eventos adversos (10/23, 43%) entre los que recibieron lopinavir/ritonavir, llevando en la mayoría de los casos a la decisión de suspender el mismo antes de completar el tratamiento. Aun con las limitaciones propias del reducido número de casos, la divulgación de dichos resultados aporta evidencia para definir el perfil de seguridad de la combinación lopinavir/ritonavir usado en enfermedad grave por SARS-CoV-2.

Topics: Adult; Aged; Argentina; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Critical Illness; Cytochrome P-450 CYP3A Inhibitors; Female; Humans; Lopinavir; Male; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; SARS-CoV-2; Treatment Outcome

Topics: Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Public Health; Ritonavir; SARS-CoV-2

Topics: Adolescent; Adult; Betacoronavirus; Chemical and Drug Induced Liver Injury; Child; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytokines; Female; Humans; Inflammation; Male; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; T-Lymphocyte Subsets; Young Adult

Topics: Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Interferon beta-1b; Lopinavir; Pandemics; Pneumonia, Viral; Ribavirin; Ritonavir; SARS-CoV-2

Topics: Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Interferon beta-1b; Lopinavir; Pandemics; Pneumonia, Viral; Ribavirin; Ritonavir; SARS-CoV-2

In December 2019, the novel coronavirus disease 2019 (COVID-19) emerged in Wuhan, Hubei Province, China. It rapidly spread and many cases were identified in multiple countries, posing a global health problem. Here, we report the first patient cured of COVID-19 infection in Changsha, China, and the symptoms, diagnosis, treatment, and management of this patient are all described in this report.. A 57-year-old woman developed cough and fever after returning to Changsha from Wuhan on January 9, 2020. She tested positive for COVID-19 infection, a diagnosis which was supported by chest CT. The patient was treated with lopinavir and ritonavir tablets and interferon alfa-2b injection. A low dose of glucocorticoids was used for a short period to control bilateral lung immune response, and this patient avoided being crushed by cytokine storms that might have occurred. The clinical condition of this patient improved, and a COVID-19 assay conducted on January 25, 2020 generated negative results. This patient recovered and was discharged on January 30, 2020.. Currently, there are numerous reports on COVID-19 infections focusing on the disease's epidemiological and clinical characteristics. This case describes the symptoms, diagnosis, treatment, and management of a patient cured of COVID-19 infection, which may serve as reference for future cases, while further studies are needed.

Topics: Betacoronavirus; China; Coronavirus Infections; Cough; COVID-19; COVID-19 Drug Treatment; Female; Fever; Glucocorticoids; HIV Protease Inhibitors; Humans; Interferon alpha-2; Lopinavir; Lung; Middle Aged; Pandemics; Pneumonia, Viral; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19.. Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). We analyze the differential cell count, ultrastructure of cells and Interleukin (IL)6, 8 and 10 levels.. ICU patients showed a marked increase in neutrophils (1.24 × 10. Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Aged; Alanine; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Female; Humans; Hydroxychloroquine; Inflammation; Intensive Care Units; Interleukin-10; Interleukin-6; Interleukin-8; Italy; Leukocytes; Leukocytes, Mononuclear; Lopinavir; Lung; Lymphocytes; Macrophages, Alveolar; Male; Microscopy, Electron, Transmission; Middle Aged; Neutrophils; Pandemics; Pneumonia, Viral; Prognosis; Prospective Studies; Respiration, Artificial; Ritonavir; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Survival Rate; Virion

The outbreak of coronavirus disease 2019 (COVID-19) has involved more than 159 countries and more than 5 million people worldwide. A 40-year-old man with a history of rheumatoid arthritis treated with prednisolone, Disease-Modifying Anti-Rheumatic Drugs (DMARDs), and biologic agents was admitted with chief complaints of fever, chills, malaise, myalgia, and dyspnea. Chest computed tomography showed bilateral subsegmental atelectasis and diffuse ground-glass opacities in both lungs inducing the suspicion of COVID-19 infection. The oro-nasopharynx swab sample for COVID-19 polymerase chain reaction was positive. In addition to supportive care, lopinavir/ritonavir 400/100 mg twice daily and oseltamivir (75 mg) twice daily were started in combination with a starting dose of hydroxychloroquine (400 mg). The methotrexate dose was decreased, and the dose of prednisolone was increased to 30 mg for 10 days. Azathioprine and adalimumab were continued at previous doses. The use of biologic agents and DMARDs in rheumatic patients is a serious challenge in the COVID-19 pandemic. In conclusion, during the COVID-19 pandemic, due to the key roles of cytokines in the promotion of the disease, the rheumatic patients may benefit from continuing their previous treatment, which may have protective effects.

Topics: Adalimumab; Adult; Antirheumatic Agents; Antiviral Agents; Arthritis, Rheumatoid; Azathioprine; Betacoronavirus; Biological Therapy; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Drug Combinations; Drug Therapy, Combination; Humans; Lopinavir; Male; Methotrexate; Oseltamivir; Pandemics; Pneumonia, Viral; Prednisolone; Ritonavir; SARS-CoV-2

We report the case of a man affected by cystic fibrosis who developed a severe SARS-CoV-2 related pneumonia in March 2020. In addition to lopinavir/ritonavir and hydroxychloroquine, he was treated with two doses of tocilizumab, displaying a significant clinical improvement. This is the first case described in the literature of an adult patient affected by cystic fibrosis who received tocilizumab for COVID-19, with documented total recovery, also assessed by a spirometry.

Topics: Adult; Antibodies, Monoclonal, Humanized; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; Cystic Fibrosis; Drug Combinations; Humans; Hydroxychloroquine; Lopinavir; Lung; Male; Oxygen Inhalation Therapy; Pneumonia, Viral; Receptors, Interleukin-6; Respiratory Function Tests; Respiratory Tract Infections; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome