zithromax and Pneumonia--Viral

The global spread of COVID-19 and the lack of definite treatment have caused an alarming crisis in the world. We aimed to evaluate the outcome and potential harmful cardiac effects of hydroxychloroquine and azithromycin compared to hydroxychloroquine alone for COVID-19 treatment.. PubMed, Medline, Google Scholar, Cochrane Library, clinicaltrials.gov, and World Health Organization clinical trial registry were searched using appropriate keywords and identified six studies using PRISMA guidelines. The quantitative synthesis was performed using fixed or random effects for the pooling of studies based on heterogeneities.. The risk of mortality (RR=1.16; CI: 0.92-1.46) and adverse cardiac events (OR=1.06; CI: 0.82-1.37) demonstrated a small increment though of no significance. There were no increased odds of mechanical ventilation (OR=0.84; CI: 0.33-2.15) and significant QTc prolongation (OR=0.84, CI: 0.59-1.21). Neither the critical QTc threshold (OR=1.92, CI: 0.81-4.56) nor absolute ?QTc ?60ms (OR=1.95, CI:0.55-6.96) increased to the level of statistical significance among hydroxychloroquine and azithromycin arm compared to hydroxychloroquine alone, but the slightly increased odds need to be considered in clinical practice.. The combination of hydroxychloroquine and azithromycin leads to small increased odds of mortality and cardiac events compared to hydroxychloroquine alone. The use of hydroxychloroquine and azithromycin led to increased odds of QT prolongation, although not statistically significant.

Topics: Azithromycin; Cardiovascular Diseases; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Humans; Hydroxychloroquine; Pneumonia, Viral; SARS-CoV-2

The rapid spread of the epidemic has aroused widespread concern in the international community. Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) was first reported in China, with bats as the likely original hosts and pangolins as potential intermediate hosts. The current source of the disease is mainly patients infected with SARS-COV-2. Patients in the incubation period may also become sources of infection. The virus is mainly transmitted via respiratory droplets and contact, and the population is generally susceptible. The epidemic has progressed through the local outbreak stage and community transmission stage due to exposure at Wuhan's Huanan wholesale seafood market and is now in the stage of large-scale transmission due to the spread of the epidemic. The basic productive number (R0) at the beginning of the epidemic was 2.2, with an average incubation period of 5.2 days. The proportion of critically ill patients was 23.4%, the mortality rate was lower than those of SARS and Middle East respiratory syndrome, and 96.5% of deaths occurred in Hubei Province, where the outbreak occurred first. Among them, elderly men with underlying diseases had a higher mortality rate. Chinese medical staff have summarized a set of effective strategies and methods in the diagnosis and treatment of this disease that are worthy of reference for their international counterparts. With powerful government intervention and the efforts of Chinese medical staff, China's outbreak has gradually improved.

Topics: Age Factors; Animals; Azithromycin; Betacoronavirus; China; Chiroptera; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Serotherapy; COVID-19 Testing; Humans; Hydroxychloroquine; Immunization, Passive; Infectious Disease Incubation Period; Pandemics; Pneumonia, Viral; Prevalence; SARS-CoV-2; Severity of Illness Index; Survival Analysis

Topics: Arrhythmias, Cardiac; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Interactions; Heart Rate; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2; Torsades de Pointes

Topics: Antiviral Agents; Arrhythmias, Cardiac; Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Monitoring, Physiologic; Pandemics; Patient Selection; Pneumonia, Viral; SARS-CoV-2

The higher death rate caused by COVID-19 in older people, especially those with comorbidities, is a challenge for biomedical aging research. Here we explore the idea that an exacerbated inflammatory response, in particular that mediated by IL-6, may drive the deleterious consequences of the infection. Data shows that other RNA viruses, such as influenza virus, can display enhanced replication efficiency in senescent cells, suggesting that the accumulation of senescent cells with aging and age-related diseases may play a role in this phenomenon. However, at present, we are completely unaware of the response to SARS-CoV and SARS-COV-2 occurring in senescent cells. We deem that this is a priority area of research because it could lead to the development of several therapeutic strategies based on senotherapeutics or prevent unsuccessful attempts. Two of these senotherapeutics, azithromycin and ruxolitinib, are currently undergoing testing for their efficacy in treating COVID-19. The potential of these strategies is not only for ameliorating the consequences of the current emergence of SARS-CoV-2, but also for the future emergence of new viruses or mutated ones for which we are completely unprepared and for which no vaccines are available.

Topics: Aging; Anti-Infective Agents; Azithromycin; Cellular Senescence; Coronavirus Infections; COVID-19; Global Health; Humans; Interleukin-6; Nitriles; Pandemics; Pneumonia, Viral; Pyrazoles; Pyrimidines

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

Coronavirus disease-2019 (COVID-19) infection and its severity can be explained by the concentration of glycosylated severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral particles in the lung epithelium, the concentration of glycosylated angiotensin-converting enzyme receptor 2 (ACE2) in the lung epithelium, and the degree and control of the pulmonary immune response to the SARS-CoV-2 spike protein at approximately day 8 to 10 after symptom onset, which may be related to both. Binding of ACE2 by SARS-CoV-2 in COVID-19 also suggests that prolonged uncontrolled hyperglycemia, and not just a history of diabetes mellitus, may be important in the pathogenesis of the disease. It is tempting to consider that the same mechanism acts in COVID-19 as in SARS, where an overactive macrophage M1 inflammatory response, as neutralizing antibodies to the SARS-CoV-2 spike protein form at day 7 to 10, results in acute respiratory distress syndrome (ARDS) in susceptible patients. It also allows consideration of agents, such as hydroxychloroquine, which may interfere with this overly brisk macrophage inflammatory response and perhaps influence the course of the disease, in particular, those that blunt but do not completely abrogate the M1 to M2 balance in macrophage polarization, as well as viral load, which in SARS appears to be temporally related to the onset of ARDS.

Topics: Angiotensin-Converting Enzyme 2; Antibodies, Neutralizing; Antibody-Dependent Cell Cytotoxicity; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Glucose; Glycosylation; Host-Pathogen Interactions; Humans; Hydroxychloroquine; Hyperglycemia; Incidence; Macrophages; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2; Spike Glycoprotein, Coronavirus

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; Rheumatologists; SARS-CoV-2

Following the demonstration of the efficacy of hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 in vitro, many trials started to evaluate its efficacy in clinical settings. However, no systematic review and meta-analysis have addressed the issue of the safety and efficacy of hydroxychloroquine (HCQ) in coronavirus disease 2019. We conducted a systematic review and meta-analysis with the objectives of evaluation of safety and efficacy of HCQ alone or in combination in terms of "time to clinical cure," "virological cure," "death or clinical worsening of disease," "radiological progression," and safety. RevMan was used for meta-analysis. We searched 16 literature databases out of which seven studies (n = 1358) were included in the systematic review. In terms of clinical cure, two studies reported possible benefit in "time to body temperature normalization" and one study reported less "cough days" in the HCQ arm. Treatment with HCQ resulted in less number of cases showing the radiological progression of lung disease (odds ratio [OR], 0.31, 95% confidence interval [CI], 0.11-0.9). No difference was observed in virological cure (OR, 2.37, 95% CI, 0.13-44.53), death or clinical worsening of disease (OR, 1.37, 95% CI, 1.37-21.97), and safety (OR, 2.19, 95% CI, 0.59-8.18), when compared with the control/conventional treatment. Five studies reported either the safety or efficacy of HCQ + azithromycin. Although seems safe and effective, more data are required for a definitive conclusion. HCQ seems to be promising in terms of less number of cases with radiological progression with a comparable safety profile to control/conventional treatment. We need more data to come to a definite conclusion.

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Clinical Trials as Topic; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome; Viral Load; Virus Replication

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells with angiotensin receptors, leading to pneumonia linked to COVID-19. The virus has a double impact on the cardiovascular system, the infection will be more intense if the host has cardiovascular co-morbidities and the virus can cause life-threatening cardiovascular lesions. Therapies associated with COVID-19 may have adverse cardiovascular effects. Therefore, special attention should be given to cardiovascular protection during COVID-19 infection.

Topics: Antimalarials; Antiviral Agents; Azithromycin; Betacoronavirus; Cardiomyopathies; Cardiovascular Diseases; Cerebrovascular Disorders; Chloroquine; Comorbidity; Coronary Disease; Coronavirus Infections; COVID-19; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hydroxychloroquine; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Methylprednisolone; Pandemics; Pneumonia, Viral; Risk Factors; SARS-CoV-2; Virus Internalization

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 expressive number of deaths and confirmed cases of SARS-CoV-2 call for an urgent demand of effective and available drugs for COVID-19 treatment. CD147, a receptor on host cells, is a novel route for SARS-CoV-2 invasion. Thus, drugs that interfere in the spike protein/CD147 interaction or CD147 expression may inhibit viral invasion and dissemination among other cells, including in progenitor/stem cells. Studies suggest beneficial effects of azithromycin in reducing viral load of hospitalized patients, possibly interfering with ligand/CD147 receptor interactions; however, its possible effects on SARS-CoV-2 invasion has not yet been evaluated. In addition to the possible effect in invasion, azithromycin decreases the expression of some metalloproteinases (downstream to CD147), induces anti-viral responses in primary human bronchial epithelial infected with rhinovirus, decreasing viral replication and release. Moreover, resident lung progenitor/stem are extensively differentiated into myofibroblasts during pulmonary fibrosis, a complication observed in COVID-19 patients. This process, and the possible direct viral invasion of progenitor/stem cells via CD147 or ACE2, could result in the decline of these cellular stocks and failing lung repair. Clinical tests with allogeneic MSCs from healthy individuals are underway to enhance endogenous lung repair and suppress inflammation.

Topics: Angiotensin-Converting Enzyme 2; Anti-Bacterial Agents; Azithromycin; B-Lymphocytes; Basigin; Betacoronavirus; Clinical Trials as Topic; Coronavirus Infections; COVID-19; Gene Expression; Host-Pathogen Interactions; Humans; Lung; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Binding; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Stem Cell Transplantation; Stem Cells; T-Lymphocytes; Viral Load

The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. As protective immunity does not exist in humans and the virus is capable of escaping innate immune responses, it can proliferate, unhindered, in primarily infected tissues. Subsequent cell death results in the release of virus particles and intracellular components to the extracellular space, which result in immune cell recruitment, the generation of immune complexes and associated damage. Infection of monocytes/macrophages and/or recruitment of uninfected immune cells can result in massive inflammatory responses later in the disease. Uncontrolled production of pro-inflammatory mediators contributes to ARDS and cytokine storm syndrome. Antiviral agents and immune modulating treatments are currently being trialled. Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.

Topics: Angiotensin-Converting Enzyme 2; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Cytokines; Disease Management; Gene Expression Regulation; Humans; Hydroxychloroquine; Immune Evasion; Immunologic Factors; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Toll-Like Receptors; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins

Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, COVID-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of COVID-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Azithromycin; Betacoronavirus; Biomarkers; Cardiovascular Diseases; Chloroquine; Comorbidity; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Disseminated Intravascular Coagulation; Extracorporeal Membrane Oxygenation; Humans; Hydroxychloroquine; Immunosuppressive Agents; Influenza, Human; Lung; Myocardium; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2; Severe Acute Respiratory Syndrome; Troponin; Venous Thromboembolism

COVID-19 infection has shown rapid growth worldwide, and different therapies have been proposed for treatment, in particular, the combination of immune response modulating drugs such as chloroquine and hydroxychloroquine (antimalarials) alone or in combination with azithromycin. Although the clinical evidence supporting their use is scarce, the off label use of these drugs has spread very quickly in face of the progression of the epidemic and the high mortality rate in susceptible populations. However, these medications can pathologically prolong the QT interval and lead to malignant ventricular arrhythmias such that organized guidance on QT evaluation and management strategies are important to reduce morbidity associated with the potential large-scale use.

Topics: Adult; Aged; Antimalarials; Arrhythmias, Cardiac; Azithromycin; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Dose-Response Relationship, Drug; Electrocardiography; Female; Humans; Hydroxychloroquine; Incidence; Long QT Syndrome; Male; Middle Aged; Pandemics; Pneumonia, Viral; Practice Guidelines as Topic; Prognosis; Risk Assessment

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

The world is currently experiencing the Coronavirus Disease-19 (COVID-19) pandemic. There is no approved drug for the definitive treatment of the disease. Various drugs are being tried for the treatment of COVID-19, including hydroxychloroquine (HCQ). This study was performed to systematically review the therapeutic role of HCQ in COVID-19 from the available literature.. PubMed, Embase, ClinicalTrials.gov, ICTRP (WHO), Cochrane Library databases, and two pre-print servers (medRxiv.org and Research Square) were searched for clinical studies that evaluated the therapeutic role of HCQ on COVID-19 until 10 May 2020. The available studies were critically analyzed and the data were extracted.. A total of 663 articles were screened and 12 clinical studies (seven peer-reviewed and published studies and five non-peer-reviewed studies from pre-print servers) with a total sample size of 3543 patients were included. Some of the clinical studies demonstrated good virological and clinical outcomes with HCQ alone or in combination with azithromycin in COVID-19 patients, although the studies had major methodological limitations. Some of the other studies showed negative results with HCQ therapy along with the risk of adverse reactions.. The results of efficacy and safety of HCQ in COVID-19, as obtained from the clinical studies, are not satisfactory, although many of these studies had major methodological limitations. Stronger evidence from well-designed robust randomized clinical trials is required before conclusively determining the role of HCQ in the treatment of COVID-19. Clinical prudence is required in advocating HCQ as a therapeutic armamentarium in COVID-19.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Clinical Trials as Topic; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral

Hydroxychloroquine (HCQ), an antimalarial has been proposed as possible treatment for coronavirus disease-2019 (COVID-19). India has approved the use of HCQ for prophylaxis of asymptomatic health workers treating suspected or confirmed COVID-19 cases, and asymptomatic household contacts of confirmed patients. The U.S. Food and Drug Administration has issued Emergency Use Authorization for the use of HCQ to treat COVID-19 in adolescents and adults. In this review, we go over the available evidence for and against HCQ's use as prophylaxis or treatment for COVID-19, especially in the Indian context.

Topics: Anti-Bacterial Agents; Antimalarials; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2

In December 2019, an outbreak of pneumonia caused by a novel coronavirus occurred in Wuhan, the capital of Central China's Hubei Province and has been declared a public health emergency of international concern by the World Health Organization since January 2020.. A comprehensive search using the PubMed database was carried out to summarize the latest published information about the epidemiology, definition, pathogenesis, clinical characteristics, treatment options, prognosis and prevention of coronavirus disease 2019.. This new strain of coronavirus, named severe acute respiratory syndrome coronavirus 2, enters human cells that express angiotensin-converting enzyme II receptors, which exist in the respiratory, gastrointestinal and genitourinary tracts and heart, causing coronavirus disease. Transmission occurs essentially through the respiratory tract and the main symptoms are fever, cough and dyspnea. Diagnosis is based on epidemiological, clinical and imaging features and confirmed by nucleic acid testing.. Despite intensive research, the exact origin of the virus and pathophysiology of coronavirus disease is not yet completely known, and clinically approved vaccines and drugs that target severe acute respiratory syndrome coronavirus 2 are lacking.. Introdução: Em dezembro de 2019, ocorreu um surto de pneumonia causada por uma nova estirpe de coronavírus em Wuhan, a capital da província de Hubei, na China central e foi declarado emergência de saúde pública de âmbito internacional pela Organização Mundial de Saúde, em janeiro de 2020. Material e Métodos: Foi realizada uma pesquisa na base de dados PubMed, de forma a sintetizar a informação mais recentemente publicada sobre a epidemiologia, definição, fisiopatologia, manifestações clínicas, tratamento, prognóstico e prevenção da doença de coronavírus 2019. Discussão: Esta nova estirpe de coronavírus, denominada coronavírus da síndrome respiratória aguda grave 2 infeta células que expressem o recetor da enzima conversora da angiotensina tipo II, existentes nos tratos respiratório, gastrointestinal e geniturinário e no coração, provocando a doença de coronavírus 2019. A transmissão ocorre essencialmente através do trato respiratório e os principais sintomas são febre, tosse e dispneia. O diagnóstico é baseado em critérios epidemiológicos, clínicos e imagiológicos, sendo a confirmação da doença realizada através da análise de ácidos nucleicos. Conclusão: Apesar da extensa investigação, ainda não é totalmente conhecida a origem do vírus, a fisiopatologia da doença e não existem vacinas nem tratamento direcionados a esta nova estirpe de coronavírus.

Topics: Adenosine Monophosphate; Alanine; Amides; Animals; Antiviral Agents; Azithromycin; Betacoronavirus; Blood Coagulation Disorders; China; Chiroptera; Chloroquine; Coronavirus Infections; COVID-19; Glucocorticoids; Humans; Hydroxychloroquine; Infectious Disease Incubation Period; Lopinavir; Lung; Pandemics; Pneumonia, Viral; Prognosis; Pyrazines; Radiography, Thoracic; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2; Symptom Assessment

The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to >187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, and myocarditis) and secondary (myocardial injury/biomarker elevation and heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a Heart-Lung team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock.

Topics: Acute Coronary Syndrome; Anti-Bacterial Agents; Antiviral Agents; Arrhythmias, Cardiac; Azithromycin; Betacoronavirus; Cardiotonic Agents; Chronic Disease; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Enzyme Inhibitors; Extracorporeal Membrane Oxygenation; Heart Failure; Heart-Assist Devices; Humans; Hydroxychloroquine; Intra-Aortic Balloon Pumping; Myocardial Infarction; Myocarditis; Pandemics; Percutaneous Coronary Intervention; Pneumonia, Viral; SARS-CoV-2; Shock, Cardiogenic; Thromboembolism

The devastating effects of the coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to urgent attempts to find effective therapeutic agents for inpatient and outpatient treatment of COVID-19. Initial enthusiasm for the combination of hydroxychloroquine and azithromycin has abated. However, as a result of positive clinical experience with azithromycin used alone during the first few days of the flu-like illness caused by this coronavirus, we recommend formal clinical trials using azithromycin early in the course of a COVID-19 infection. There is one clinical trial initiated, the individually randomized, telemedicine-based, "Azithromycin for COVID-19 Treatment in Outpatients Nationwide" based at the University of California San Francisco. This placebo-controlled trial is designed to determine the efficacy of a single 1.2-g dose of oral azithromycin to prevent COVID-19 patient progression to hospitalization. We recommend formal clinical trials of azithromycin in its prepackaged form at the first sign of COVID-19 infection in adults and children, using an initial adult dose of 500 mg followed by 250 mg per day for 4 days, a total cumulative dose of 1.5 g, and for children 5 to 18 years of age, 10 mg/kg on the first day followed by 5 mg/kg for 4 days.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Betacoronavirus; Child; Coronavirus Infections; COVID-19; Dose-Response Relationship, Drug; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2

The emergence of the new COVID-19 virus is proving to be a challenge in seeking effective therapies. Since the most severe clinical manifestation of COVID-19 appears to be a severe acute respiratory syndrome, azithromycin has been proposed as a potential treatment. Azithromycin is known to have immunomodulating and antiviral properties. In vitro studies have demonstrated the capacity of azithromycin in reducing production of pro-inflammatory cytokines such as IL-8, IL-6, TNF alpha, reduce oxidative stress, and modulate T-helper functions. At the same time there are multiple clinical evidences of the role of azithromycin in acute respiratory distress syndrome and against Middle East Respiratory syndrome (MERS). Some preliminary evidence has demonstrated controversial results regarding efficacy of azithromycin in combination with hydroxychloroquine in COVID-19. First, a French trial demonstrated 100% virological negativizing of six patients treated with azithromycin plus hydroxychloroquine vs. 57.1% of patients treated with only hydroxychloroquine and 12.5% of the control group (P < 0.05). On the other hand, another case series revealed no efficacy at all on 11 patients treated with the same combination and doses. Furthermore, there are some concerns regarding the association of azithromycin and hydroxychloroquine because of potential QT prolongation. In fact, both drugs have this as a potential side effect and evidence regarding the safe use of this combination is controversial. Despite the necessity to quickly find solutions for COVID-19, extreme caution must be used in evaluating the risk-benefit balance. However, based on preclinical and clinical evidence and some preliminary results in COVID-19, azithromycin could have potential in the fight against this new disease.

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Humans; Hydroxychloroquine; Immunologic Factors; Long QT Syndrome; Pandemics; Pneumonia, Viral; SARS-CoV-2

COVID-19 is a severe pandemic which has caused a devastating amount of loss in lives around the world, and yet we still don't know how to appropriately treat this disease. We know very little about the pathogenesis of SARS-CoV-2, the virus which induces the COVID-19. However, COVID-19 does share many similar symptoms with SARS and influenza. Previous scientific discoveries learned from lab animal models and clinical practices shed light on possible pathogenic mechanisms in COVID-19. In the past decades, accumulated scientific findings confirmed the pathogenic role of free radicals damage in respiratory virus infection. Astonishingly very few medical professionals mention the crucial role of free radical damage in COVID-19. This hypothesis aims to summarize the crucial pathogenic role of free radical damage in respiratory virus induced pneumonia and suggest an antioxidative therapeutic strategy for COVID-19.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Azithromycin; Betacoronavirus; Clinical Trials as Topic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytokine Release Syndrome; Drug Therapy, Combination; Free Radicals; Glutathione; Humans; Hydroxychloroquine; Mice; Multiple Organ Failure; NF-E2-Related Factor 2; Nitric Oxide; Orthomyxoviridae Infections; Oxidative Stress; Pandemics; Pneumonia, Viral; Reactive Oxygen Species; SARS-CoV-2; Severe Acute Respiratory Syndrome

Topics: Azithromycin; Betacoronavirus; Biomarkers; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Diagnosis, Differential; Drug Therapy, Combination; Humans; Hydroxychloroquine; Hypoxia; Long QT Syndrome; Myocardial Infarction; Myocarditis; Pandemics; Pericarditis; Pneumonia, Viral; SARS-CoV-2; Systemic Inflammatory Response Syndrome; Tachycardia, Ventricular; Thrombophilia; Ventricular Dysfunction, Left; Ventricular Fibrillation

In the midst of a pandemic, finding effective treatments for coronavirus disease 2019 (COVID-19) is the urgent issue. In "chronic inflammatory diseases", the overexpression of delayed rectifier K

Topics: Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Cytokines; Drug Delivery Systems; Humans; Kv1.3 Potassium Channel; Lymphocytes; Pandemics; Pneumonia, Viral; SARS-CoV-2; Severity of Illness Index

Topics: Adenosine Monophosphate; Alanine; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antimalarials; Antiviral Agents; Azithromycin; Betacoronavirus; Biological Products; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Serotherapy; Humans; Hydroxychloroquine; Immunization, Passive; Non-Randomized Controlled Trials as Topic; Pandemics; Pneumonia, Viral; Protease Inhibitors; Protein-Tyrosine Kinases; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; Viral Load

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

The severity of COVID-19 has resulted in a global rush to find the right antiviral treatment to conquer the pandemic and to treat patients. This requires reliable studies to support treatment. In a recently published study by Gautret et al. the authors concluded that hydroxychloroquine monotherapy and hydroxychloroquine in combination with azithromycin reduced viral load. However, this trial has several major methodological issues, including the design, outcome measure and the statistical analyses. In this paper we discuss the background, clinical evidence, pharmacology and methodological issues related to this clinical trial. We understand the rush to release results, however in case conclusions are far reaching the evidence needs to be robust.

Topics: Azithromycin; Betacoronavirus; Clinical Trials as Topic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Humans; Hydroxychloroquine; Outcome Assessment, Health Care; Pandemics; Pneumonia, Viral; Research Design; SARS-CoV-2

The global COVID-19 pandemic has led to a race to find medications that can improve the prognosis of the disease. Azithromycin, in association with hydroxychloroquine or chloroquine, has been proposed as one such medication. The aim of this review is to describe the pharmacological mechanism, clinical evidence and prescribing guidelines concerning azithromycin in COVID-19 patients. There is weak evidence on the antiviral and immunomodulating effects of azithromycin, which in addition is not based on results from COVID-19 patients specifically. Therefore, this antibacterial should be considered only as empirical treatment of community-acquired pneumonia (CAP), although not all current treatment guidelines are in agreement. After the initial expectations raised by a small trial, more recent evidence has raised serious safety concerns on the use of hydroxychloroquine or chloroquine with azithromycin to treat COVID-19 patients, as all these drugs have arrhythmogenic potential. The World Health Organization has not made recommendations suggesting the use of azithromycin with hydroxychloroquine or chloroquine as treatment for COVID-19, but some national organisations have taken a different position, recommending this as first-line treatment. Several scientific societies, including the American College of Cardiology, have cautioned about the risks of this treatment in view of the lack of evidence concerning its benefits.

Topics: Anti-Bacterial Agents; Azithromycin; Betacoronavirus; Coinfection; Coronavirus Infections; COVID-19; Humans; Medication Therapy Management; Pandemics; Patient Selection; Pneumonia, Viral; Practice Guidelines as Topic; SARS-CoV-2; Treatment Outcome

Given the speed of viral infection spread, repurposing of existing drugs has been given the highest priority in combating the ongoing COVID-19 pandemic. Only drugs that are already registered or close to registration, and therefore have passed lengthy safety assessments, have a chance to be tested in clinical trials and reach patients quickly enough to help in the current disease outbreak. Here, we have reviewed available evidence and possible ways forward to identify already existing pharmaceuticals displaying modest broad-spectrum antiviral activity which is likely linked to their high accumulation in cells. Several well studied examples indicate that these drugs accumulate in lysosomes, endosomes and biological membranes in general, and thereby interfere with endosomal pathway and intracellular membrane trafficking crucial for viral infection. With the aim to identify other lysosomotropic drugs with possible inherent antiviral activity, we have applied a set of clear physicochemical, pharmacokinetic and molecular criteria on 530 existing drugs. In addition to publicly available data, we have also used our in silico model for the prediction of accumulation in lysosomes and endosomes. By this approach we have identified 36 compounds with possible antiviral effects, also against coronaviruses. For 14 of them evidence of broad-spectrum antiviral activity has already been reported, adding support to the value of this approach. Presented pros and cons, knowledge gaps and methods to identify lysosomotropic antivirals, can help in the evaluation of many drugs currently in clinical trials considered for repurposing to target COVID-19, as well as open doors to finding more potent and safer alternatives.

Topics: Anti-Inflammatory Agents; Antiviral Agents; Arrhythmias, Cardiac; Azithromycin; Betacoronavirus; Chemical and Drug Induced Liver Injury; Chloroquine; Computer Simulation; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Evaluation, Preclinical; Drug Repositioning; Endosomes; Humans; Hydrogen-Ion Concentration; Hydroxychloroquine; Intracellular Membranes; Lysosomes; Membrane Lipids; Models, Biological; Pandemics; Phospholipids; Pneumonia, Viral; SARS-CoV-2; Surface-Active Agents; Virus Internalization

Recent small-scale clinical trials have shown promising results in the use of hydroxychloroquine, an FDA approved anti-malaria drug, for the treatment of COVID-19. However, large scale, randomized and double-blind clinical trials are needed to confirm the safety and efficacy of hydroxychloroquine in COVID-19 patients. Here, we review the progress of using hydroxychloroquine or chloroquine as anti-viral agents, failed clinical trials of chloroquine in treatment of dengue virus and influenza infection, and especially the mechanism of azithromycin in inhibiting viral replication, so as to shed light on the ongoing clinical trials and further researches of hydroxychloroquine on SARS-CoV-2 infected patients.

Topics: Animals; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Disease Models, Animal; Drug Therapy, Combination; Humans; Hydroxychloroquine; Mice; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome; Virus Replication

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mainly affects the lungs. Sarcoidosis is an autoinflammatory disease characterized by the diffusion of granulomas in the lungs and other organs. Here, we discuss how the two diseases might involve some common mechanistic cellular pathways around the regulation of autophagy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Autophagy; Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Host-Pathogen Interactions; Humans; Isoniazid; Lung; Pandemics; Pneumonia, Viral; Pulmonary Edema; Rifampin; Sarcoidosis; SARS-CoV-2; Severe Acute Respiratory Syndrome; Severity of Illness Index

The Strategic Plan for Biodefense Research by the U.S. Department of Health and Human Services demarcates the need for drugs which target multiple types of pathogens to prepare for infectious threats. Azithromycin is one such broad-spectrum therapeutic that is both included in the University of Oxford's RECOVERY and excluded from the World Health Organization's SOLIDARITY trials. Here we review azithromycin's broad antibiotic, antimalarial, antiviral pharmacology and contextualise it against a broader history as the most repositioned therapeutic of the macrolide class; we further evaluate azithromycin's clinical and socio-economic propriety for respiratory pandemics and delineate a model for its combinatorial mechanism of action against COVID-19 pneumonia.

Topics: Animals; Anti-Inflammatory Agents; Antiviral Agents; Azithromycin; Betacoronavirus; Cell Line, Tumor; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Immunologic Factors; Macrophages; Pandemics; Pneumonia, Viral; SARS-CoV-2

In December 2019, a new strain of the SARS-CoV-2 coronavirus was reported in Wuhan, China, which produced severe lung involvement and progressed to respiratory distress. To date, more than seventeen million confirmed cases and more than half a million died worldwide from COVID-19. Patients with cardiovascular disease are more susceptible to contracting this disease and presenting more complications. We did a literature search on the association of cardiovascular disease and COVID-19 in databases such as Scopus, PubMed/MEDLINE, and the Cochrane Library. The purpose of this review is to provide updated information for health professionals who care for patients with COVID-19 and cardiovascular disease, given that they have a high risk of complications and mortality. Treatment with angiotensin-converting enzyme inhibitors and receptor blockers is controversial, and there is no evidence not to use these medications in patients with COVID-19. Regarding treatment with hydroxychloroquine associated or not with azithromycin, there is evidence of a higher risk with its use than clinical benefit and decreased mortality. Likewise, patients with heart failure are an important risk group due to their condition per se. Patients with heart failure and COVID-19 are a diagnostic dilemma because the signs of acute heart failure could be masked. On the other hand, in patients with acute coronary syndrome, the initial therapeutic approach could change in the context of the pandemic, although only based on expert opinions. Nonetheless, many controversial issues will be the subject of future research.. En diciembre de 2019 se reportó en Wuhan, China, la aparición de una nueva cepa de coronavirus SARS-CoV-2 que producía un compromiso pulmonar severo y progresaba a estrés respiratorio agudo. A la fecha, son más de diecisiete millones los casos confirmados y más de medio millón los fallecidos en todo el mundo a causa de COVID-19. Los estudios reportan que los pacientes con enfermedad cardiovascular son más susceptibles a contraer esta enfermedad y a presentar más complicaciones. El propósito de esta revisión es proporcionar información actualizada para los profesionales de la salud que atienden a pacientes con COVID-19 y que tienen además enfermedad cardiovascular y por ende un riesgo elevado de complicaciones y mortalidad. Realizamos una búsqueda de bibliografía científica acerca de la asociación de enfermedad cardiovascular y COVID-19 en diferentes bases de datos como Scopus, MEDLINE vía PubMed y Cochrane Library. El tratamiento con inhibidores de la enzima convertidora de angiotensina y bloqueadores del receptor de angiotensina ha sido motivo de discusión y no hay evidencia sólida para contraindicarlo en pacientes con COVID-19. Respecto al tratamiento con hidroxicloroquina asociado o no con azitromicina, hay evidencia que demuestra un mayor riesgo con su utilización, que beneficio clínico y/o disminución de mortalidad. En este contexto, los pacientes con insuficiencia cardíaca representan un grupo importante de riesgo por su condición per se y por el dilema diagnóstico generado al evaluar un paciente con COVID-19, en el que los signos de insuficiencia cardíaca aguda podrían enmascararse. Por otro lado, en los pacientes con síndrome coronario agudo, el enfoque terapéutico inicial podría cambiar en el contexto de la pandemia, aunque sólo sobre la base de opiniones de expertos. Quedan, sin embargo, muchos temas en controversia que serán motivo de investigaciones futuras.

Topics: Acute Coronary Syndrome; Algorithms; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Antiviral Agents; Azithromycin; Betacoronavirus; Cardiovascular Diseases; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Electrocardiography; Heart Failure; Humans; Hydroxychloroquine; Hypertension; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Prognosis; Renin-Angiotensin System; SARS-CoV-2

Coronavirus disease 2019 (COVID-19), which is caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has recently emerged as a global health threat. To address this health emergency, various therapeutic approaches are currently under investigation. There is limited evidence on the effectiveness of hydroxychloroquine (HCQ) and chloroquine (CQ) as COVID-19 therapies, and thus World Health Organization (WHO) mentioned that "Current data shows that this drug does not reduce deaths among hospitalized COVID-19 patients, nor help people with mild or moderate disease." CQ and HCQ are typically used for the treatment of malaria but have been recognized for certain beneficial effects in COVID-19 patients based on some clinical outcomes from the clinical treatment of COVID-19. A standard dose of HCQ has been proven effective and less toxic than CQ in COVID-19 patients; however, a comprehensive understanding of a patient's clinical condition is necessary. Based on several hospital findings, the Food and Drug Administration (FDA) has officially cancelled the emergency use authorization for HCQ and CQ for treating hospitalized COVID-19 patients on June 15, 2020. In this review, we highlight both pros and cons of the clinical use of CQ and HCQ in COVID-19 patients.

Topics: Anti-Infective Agents; Azithromycin; Betacoronavirus; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; COVID-19; Drug Synergism; Humans; Hydroxychloroquine; Immunologic Factors; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Pandemics; Personal Protective Equipment; Pneumonia, Viral; Randomized Controlled Trials as Topic; SARS-CoV-2

Community-acquired pneumonia (CAP) occurs more often in early childhood than at almost any other age. Many microorganisms are associated with pneumonia, but individual pathogens are difficult to identify, which poses problems in antibiotic management. This article reviews the common as well as new, emerging pathogens, as well as the guidelines for management of pediatric CAP. Current guidelines for pediatric CAP continue to recommend the use of high-dose amoxicillin for bacterial CAP and azithromycin for suspected atypical CAP (usually caused by Mycoplasma pneumoniae) in children.

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Community-Acquired Infections; Diagnosis, Differential; Drug Administration Schedule; Drug Resistance, Bacterial; Humans; Medical History Taking; Physical Examination; Pneumonia, Bacterial; Pneumonia, Viral; Severity of Illness Index

An effective treatment option is not yet available for SARS-CoV2, which causes the COVID-19 pandemic and whose effects are felt more and more every day. Ivermectin is among the drugs whose effectiveness in treatment has been investigated. In this study; it was aimed to investigate the presence of gene mutations that alter ivermectin metabolism and cause toxic effects in patients with severe COVID-19 pneumonia, and to evaluate the effectiveness and safety of ivermectin use in the treatment of patients without mutation.. Patients with severe COVID19 pneumonia were included in the study, which was planned as a prospective, randomized, controlled, single-blind phase 3 study. Two groups, the study group and the control group, took part in the study. Ivermectin 200 mcg/kg/day for 5 days in the form of a solution prepared for enteral use added to the reference treatment protocol -hydroxychloroquine + favipiravir + azithromycin- of patients included in the study group. Patients in the control group were given only reference treatment with 3 other drugs without ivermectin. The presence of mutations was investigated by performing sequence analysis in the mdr1/abcab1 gene with the Sanger method in patients included in the study group according to randomization. Patients with mutations were excluded from the study and ivermectin treatment was not continued. Patients were followed for 5 days after treatment. At the end of the treatment and follow-up period, clinical response and changes in laboratory parameters were evaluated.. A total of 66 patients, 36 in the study group and 30 in the control group were included in the study. Mutations affecting ivermectin metabolism was detected in genetic tests of six (16.7%) patients in the study group and they were excluded from the study. At the end of the 5-day follow-up period, the rate of clinical improvement was 73.3% (22/30) in the study group and was 53.3% (16/30) in the control group (p = 0.10). At the end of the study, mortality developed in 6 patients (20%) in the study group and in 9 (30%) patients in the control group (p = 0.37). At the end of the follow-up period, the average peripheral capillary oxygen saturation (SpO2) values of the study and control groups were found to be 93.5 and 93.0%, respectively. Partial pressure of oxygen (PaO2)/FiO2 ratios were determined as 236.3 ± 85.7 and 220.8 ± 127.3 in the study and control groups, respectively. While the blood lymphocyte count was higher in the study group compared to the control group (1698 ± 1438 and 1256 ± 710, respectively) at the end of the follow-up period (p = 0.24); reduction in serum C-reactive protein (CRP), ferritin and D-dimer levels was more pronounced in the study group (p = 0.02, p = 0.005 and p = 0.03, respectively).. According to the findings obtained, ivermectin can provide an increase in clinical recovery, improvement in prognostic laboratory parameters and a decrease in mortality rates even when used in patients with severe COVID-19. Consequently, ivermectin should be considered as an alternative drug that can be used in the treatment of COVID-19 disease or as an additional option to existing protocols.

Topics: Aged; Amides; Antiviral Agents; ATP Binding Cassette Transporter, Subfamily B; Azithromycin; COVID-19; COVID-19 Drug Treatment; Cytochrome P-450 CYP3A; Drug Therapy, Combination; Female; Humans; Hydroxychloroquine; Ivermectin; Male; Middle Aged; Pneumonia, Viral; Prospective Studies; Pyrazines; Single-Blind Method; Treatment Outcome

Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads.. French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16. Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.. Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

Topics: Adult; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Female; Humans; Hydroxychloroquine; Male; Middle Aged; Pandemics; Pneumonia, Viral; Polymerase Chain Reaction; SARS-CoV-2; Viral Load

Topics: Adult; Aged; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Female; Humans; Hydroxychloroquine; Male; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome; Young Adult

There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug.. To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19.. This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon.. Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days).. Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4.. Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%).. The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19.. ClinicalTrials.gov Identifier: NCT04323527.

Topics: Adult; Aged; Anti-Bacterial Agents; Antiviral Agents; Azithromycin; Betacoronavirus; Brazil; Chloroquine; Coronavirus Infections; COVID-19; Disease Outbreaks; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Oseltamivir; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tertiary Care Centers

Coronavirus disease (COVID-19) is a potentially fatal illness with no proven therapy beyond excellent supportive care. Treatments are urgently sought. Adaptations to traditional trial logistics and design to allow rapid implementation, evaluation of trials within a global trials context, flexible interim monitoring, and access outside traditional research hospitals (even in settings where formal placebos are unavailable) may be helpful. Thoughtful adaptations to traditional trial designs, especially within the global context of related studies, may also foster collaborative relationships among government, community, and the research enterprise. Here, we describe the protocol for a pragmatic, active comparator trial in as many as 300 patients comparing two current "off-label" treatments for COVID-19-hydroxychloroquine and azithromycin-in academic and nonacademic hospitals in Utah. We developed the trial in response to local pressures for widespread, indiscriminate off-label use of these medications. We used a hybrid Bayesian-frequentist design for interim monitoring to allow rapid, contextual assessment of the available evidence. We also developed an inference grid for interpreting the range of possible results from this trial within the context of parallel trials and prepared for a network meta-analysis of the resulting data. This trial was prospectively registered (ClinicalTrials.gov Identifier: NCT04329832) before enrollment of the first patient.Clinical trial registered with www.clinicaltrials.gov (NCT04329832).

Topics: Adult; Anti-Infective Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Monitoring; Female; Humans; Hydroxychloroquine; Male; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome; Utah

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Disease Progression; Drug Administration Schedule; Health Status; Humans; Hydroxychloroquine; Ireland; Multicenter Studies as Topic; Pandemics; Pneumonia, Viral; Prospective Studies; Randomized Controlled Trials as Topic; SARS-CoV-2; Time Factors; Treatment Outcome

The aim of this randomised GCP-controlled trial is to clarify whether combination therapy with the antibiotic azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy and pre-emptive treatment of supra-infections can shorten hospitalisation duration for patients with COVID-19 (measured as "days alive and out of hospital" as the primary outcome), reduce the risk of non- invasive ventilation, treatment in the intensive care unit and death.. This is a multi-centre, randomised, Placebo-controlled, 2-arm ratio 1:1, parallel group double-blind study.. 226 participants are recruited at the trial sites/hospitals, where the study will take place in Denmark: Aalborg, Bispebjerg, Gentofte, Herlev, Hillerød, Hvidovre, Odense and Slagelse hospitals.. • Patient admitted to Danish emergency departments, respiratory medicine departments or internal medicine departments • Age≥ 18 years • Hospitalized ≤48 hours • Positive COVID-19 test / diagnosis during the hospitalization (confirmed). • Men or non-fertile women. Fertile women* must not be pregnant, i.e. negative pregnancy test must be available at inclusion • Informed consent signed by the patient *Defined as after menarche and until postmenopausal (no menstruation for 12 months) Exclusion criteria: • At the time of recruitment, the patient uses >5 LO2/min (equivalent to 40% FiO2 if measured) • Known intolerance/allergy to azithromycin or hydroxychloroquine or hypersensitivity to quinine or 4-aminoquinoline derivatives • Neurogenic hearing loss • Psoriasis • Retinopathy • Maculopathy • Visual field changes • Breastfeeding • Severe liver diseases other than amoebiasis (INR> 1.5 spontaneously) • Severe gastrointestinal, neurological and hematological disorders (investigator-assessed) • eGFR <45 ml/min/1.73 m2 • Clinically significant cardiac conduction disorders/arrhythmias or prolonged QTc interval (QTc (f) of> 480/470 ms). • Myasthenia gravis • Treatment with digoxin* • Glucose-6-phosphate dehydrogenase deficiency • Porphyria • Hypoglycaemia (Blood glucose at any time since hospitalization of <3.0 mmol/L) • Severe mental illness which significantly impedes cooperation • Severe linguistic problems that significantly hinder cooperation • Treatment with ergot alkaloids *The patient must not be treated with digoxin for the duration of the intervention. For atrial fibrillation/flutter, select according to the Cardiovascular National Treatment Guide (NBV): Calcium antagonist, Beta blocker, direct current (DC) conversion or amiodarone. In case of urgent need for digoxin treatment (contraindication for the aforementioned equal alternatives), the test drug should be paused, and ECG should be taken daily.. Control group: The control group will receive the standard treatment + placebo for both types of intervention medication at all times. If part or all the intervention therapy being investigated becomes standard treatment during the study, this may also be offered to the control group. Intervention group: The patients in the intervention group will also receive standard care. Immediately after randomisation to the intervention group, the patient will begin treatment with: Azithromycin: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 If the patient is unable to take the medication orally by themselves, the medication will, if possible, be administered by either stomach-feeding tube, or alternatively, temporary be changed to clarithromycin 500 mg x 2 (this only in agreement with either study coordinator Pradeesh Sivapalan or principal investigator Jens-Ulrik Stæhr Jensen). This will also be done in the control group if necessary. The patient will switch back to azithromycin when possible. Hydroxychloroquine: Furthermore, the patient will be treated with hydroxychloroquine as follows: Day 1-15: 200 mg x 2 MAIN OUTCOMES: • Number of days alive and discharged from hospital within 14 days (summarises both whether the patient is alive and discharged from hospital) ("Days alive and out of hospital") RANDOMISATION: The sponsor (Chronic Obstructive Pulmonary Disease Trial Network, COP:TRIN) generates a randomisation sequence. Randomisation will be in blocks of unknown size and the final allocation will be via an encrypted website (REDCap). There will be stratification for age (>70 years vs. <=70 years), site of recruitment and whether the patient has any of the following chronic lung diseases: COPD, asthma, bronchiectasis, interstitial lung disease (Yes vs. No).. Participants and study personnel will both be blinded, i.e. neither will know which group the participant is allocated to.. This study requires 226 patients randomised 1:1 with 113 in each group.. Protocol version 1.8, from April 16, 2020. Recruitment is ongoing (first patient recruited April 6, 2020; final patient expected to be recruited October 31, 2020).. ClinicalTrials.gov Identifier: NCT04322396 (registered March 26, 2020) FULL PROTOCOL: 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Critical Care; Denmark; Double-Blind Method; Drug Administration Schedule; Hospital Mortality; Host-Pathogen Interactions; Humans; Hydroxychloroquine; Inpatients; Length of Stay; Multicenter Studies as Topic; Noninvasive Ventilation; Pandemics; Patient Admission; Pneumonia, Viral; Randomized Controlled Trials as Topic; SARS-CoV-2; Severity of Illness Index; Time Factors; Treatment Outcome

Novel coronavirus SARS-CoV-2 is known to be susceptible in vitro to exposure to hydroxychloroquine and its effect has been found to be potentiated by azithromycin. We hypothesise that early administration of hydroxychloroquine alone or in combination with azithromycin can prevent respiratory deterioration in patients admitted to intensive care due to rapidly progressive COVID-19 infection.. Design: Prospective, multi-centre, double-blind, randomised, controlled trial (RCT).. Adult (> 18 years) within 24 h of admission to the intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria include duration symptoms of febrile disease for ≥ 1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, and pregnancy.. Patients will be randomised in 1:1:1 ratio to receive Hydroxychloroquine 800 mg orally in two doses followed by 400 mg daily in two doses and azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or hydroxychloroquine + placebo (HC group) or placebo + placebo (C-group) in addition to the best standard of care, which may evolve during the trial period but will not differ between groups. Primary outcome is the composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14.. The percentage of patients who were prevented from needing intubation until day 14, ICU length of stay, and mortality (in hospital) at day 28 and 90.. Although both investigational drugs are often administered off label to patients with severe COVID-19, at present, there is no data from RCTs on their safety and efficacy. In vitro and observational trial suggests their potential to limit viral replication and the damage to lungs as the most common reason for ICU admission. Therefore, patients most likely to benefit from the treatment are those with severe but early disease. This trial is designed and powered to investigate whether the treatment in this cohort of patients leads to improved clinical patient-centred outcomes, such as mechanical ventilation-free survival.. Clinical trials.gov: NCT04339816 (Registered on 9 April 2020, amended on 22 June 2020); Eudra CT number: 2020-001456-18 (Registered on 29 March 2020).

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Double-Blind Method; Drug Therapy, Combination; Humans; Hydroxychloroquine; Intensive Care Units; Pandemics; Pneumonia, Viral; Prospective Studies; Randomized Controlled Trials as Topic; SARS-CoV-2

Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited.. We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed.. A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent.. Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).

Topics: Adult; Aged; Aged, 80 and over; Antiviral Agents; Azithromycin; Betacoronavirus; Brazil; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Female; Hospitalization; Humans; Hydroxychloroquine; Male; Middle Aged; Pandemics; Patient Acuity; Pneumonia, Viral; SARS-CoV-2; Treatment Failure

To evaluate the effectiveness of Hydroxychloroquine Phosphate/Sulfate (200 mg orally 8 hourly thrice a day for 5 days), versus oseltamivir (75 mg orally twice a day for 5 days), and versus Azithromycin (500 mg orally daily on day 1, followed by 250 mg orally twice a day on days 2-5) alone and in combination (in all seven groups), in clearing the coronavirus (COVID-19) nucleic acid from throat and nasal swab and in bringing about clinical improvement on day 7 of follow-up (primary outcomes).. An adaptive design, set within a comprehensive cohort study, to permit flexibility in this fast-changing clinical and public health scenario. The randomized study will be a multicenter, multiarm, multistage, randomized controlled trial with a parallel design. An observation only cohort will emerge from those not consenting to randomization.. Eligible will be newly diagnosed patients, either hospitalized or in self-isolation, without any comorbidities or with controlled chronic medical conditions like diabetes mellitus and hypertension. Participants of any gender or age group having tested positive for COVID-19 on Real-Time qRT-PCR (Quantitative Reverse Transcription PCR) will be invited to take part in study at twelve centers across eight cities in Pakistan. Those pregnant or lactating, severely dyspneic or with respiratory distress, already undergoing treatment, and with serious comorbidities like liver or kidney failure will be excluded.. There will be a total of seven comparator groups: Each drug (Hydroxychloroquine Phosphate/Sulfate, Oseltamivir and Azithromycin) given as monotherapy (three groups); combinations of each of two drugs (three groups); and a final group on triple drug regimen.. The laboratory-based primary outcome will be turning the test negative for COVID-19 on qRT-PCR on day 7 of follow-up. The clinical primary outcome will be improvement from baseline of two points on a seven-category ordinal scale of clinical status on day 7 of follow-up.. Participants will be randomized, maintaining concealment of allocation sequence, using a computer-generated random number list of variable block size into multiple intervention groups in the allocation ratio of 1:1 for all groups.. This is an open label study, neither physician nor participants will be blinded.. This is an adaptive design and parameters for formal sample size calculation in a new disease of a previously unknown virus are not available. Thus, the final sample size will be subjected to periodic reviews at each stage of adaptive design and subsequent advice of National Data Safety & Management Board (NDSMB) notified by Drug Regulatory Authority of Pakistan.. Protocol Version 1.7 dated July 5, 2020. By July 03, 2020, the trial had recruited a total of about 470 participants across 12 centers after approval from the National Bioethics Committee and Drug Regulatory Authority of Pakistan. Recruitment started on April 20, 2020. The recruitment is expected to continue for at least three months subject to review by the National Data Safety and Management Board (NDSMB) notified by Drug Regulatory Authority of Pakistan.. Prospectively registered on 8 April 2020 at clinicaltrials.gov ID: NCT04338698 The full protocol is attached as an additional file, accessible from the Trials website (Additional file1). 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file2).

Topics: Azithromycin; Betacoronavirus; Comorbidity; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Oseltamivir; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Research Design; SARS-CoV-2

Azithromycin is an orally active synthetic macrolide antibiotic with a wide range of anti-bacterial, anti-inflammatory and antiviral properties. It is a safe, inexpensive, generic licenced drug available worldwide and manufactured to scale and is a potential candidate therapy for pandemic coronavirus disease 2019 (COVID-19). Azithromycin was widely used to treat severe SARS-CoV and MERS-CoV, but to date, no randomised data are available in any coronavirus infections. Other ongoing trials are exploring short courses of azithromycin either in early disease, within the first 7 days of symptoms, when azithromycin's antiviral properties may be important, or late in disease when anti-bacterial properties may reduce the risk of secondary bacterial infection. However, the molecule's anti-inflammatory properties, including suppression of pulmonary macrophage-derived pro-inflammatory cytokines such as interleukins-1β, -6, -8, and -18 and cytokines G-CSF and GM-CSF may provide a distinct therapeutic benefit if given in as a prolonged course during the period of progression from moderate to severe disease.. ATOMIC2 is a phase II/III, multi-centre, prospective, open-label, two-arm randomised superiority clinical trial of azithromycin versus standard care for adults presenting to hospital with COVID-19 symptoms who are not admitted at initial presentation. We will enrol adults, ≥ 18 years of age assessed in acute hospitals in the UK with clinical diagnosis of COVID-19 infection where management on an ambulatory care pathway is deemed appropriate. Participants will be randomised in a 1:1 ratio to usual care or to azithromycin 500 mg orally daily for 14 days with telephone follow-up at days 14 and 28. The primary objective is to compare the proportion with either death or respiratory failure requiring invasive or non-invasive mechanical ventilation over 28 days from randomisation. Secondary objectives include mortality/respiratory failure in those with a PCR-confirmed diagnosis; all-cause mortality; progression to pneumonia; progression to severe pneumonia; peak severity of illness and mechanistic analysis of blood and nasal biomarkers.. This trial will determine the clinical utility of azithromycin in patients with moderately severe, clinically diagnosed COVID-19 and could be rapidly applicable worldwide.. ClinicalTrials.gov NCT04381962 . Registered on 11 May 2020. EudraCT identifier 2020-001740-26 . Opened for accrual on 29 May 2020.

Topics: Anti-Bacterial Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Pandemics; Pneumonia, Viral; Prospective Studies; Randomized Controlled Trials as Topic; Research Design; SARS-CoV-2; Severity of Illness Index

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

The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19.. We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278.. 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94-1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups.. In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19.. COALITION COVID-19 Brazil and EMS.

Topics: Aged; Antiviral Agents; Azithromycin; Betacoronavirus; Brazil; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Female; Humans; Hydroxychloroquine; Length of Stay; Male; Middle Aged; Pandemics; Pneumonia, Viral; Respiratory Therapy; SARS-CoV-2; Standard of Care; Treatment Outcome

There is an urgent need for treatments that can shorten hospitalization and lower the risk of secondary infection and death in patients with corona disease. The ProPac-COVID trial evaluates whether combination therapy with macrolide azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy, and pre-emptive treatment of supra-infections can shorten hospitalization duration and reduce the risk of non-invasive ventilation, treatment in the intensive care unit, and death in patients with acute hospital admission and a positive test for 2019-nCoV and symptoms of COVID-19 disease.. The ProPAC-COVID is a multi-center, randomized, placebo-controlled, double-blinded clinical trial. The primary outcome is number of days spent alive and out of hospital within 14 days from randomization. Randomization will be in blocks of unknown size, and the final allocation will be stratified for age, site of recruitment, and whether the patient has any chronic lung diseases. Data is analyzed using intention-to-treat (ITT) principles, and main analyses will also be subject to modified ITT analysis and per protocol analysis.. This paper describes the detailed statistical analysis plan for the evaluation of primary and secondary endpoints of the ProPAC-COVID study. Enrolment of patients to the ProPAC-COVID study is still ongoing. The purpose of this paper is to provide primary publication of study results to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency.. ClinicalTrials.gov NCT04322396 . Registered on 26 March 2020.

Topics: Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antimalarials; Azithromycin; Betacoronavirus; Case-Control Studies; Coronavirus Infections; COVID-19; Denmark; Double-Blind Method; Drug Therapy, Combination; Female; Hospital Mortality; Hospitalization; Humans; Hydroxychloroquine; Intensive Care Units; Intention to Treat Analysis; Male; Noninvasive Ventilation; Pandemics; Placebos; Pneumonia, Viral; Risk Reduction Behavior; SARS-CoV-2

To determine the etiology of community-acquired pneumonia in ambulatory children and to compare responses to treatment with azithromycin, amoxicillin-clavulanate or erythromycin estolate.. Ambulatory patients with pneumonia were identified at the Children's Medical Center of Dallas, TX. Children age 6 months to 16 years with radiographic and clinical evidence of pneumonia were enrolled and randomized to receive either azithromycin suspension for 5 days or a 10-day course of amoxicillin-clavulanate for those <5 years or erythromycin estolate suspension for those > or = 5 years. Blood culture was obtained in all patients and we obtained nasopharyngeal and pharyngeal swabs for culture and polymerase chain reaction (PCR) testing for Chlamydia pneumoniae and Mycoplasma pneumoniae and nasopharyngeal swabs for viral direct fluorescent antibody and culture. Acute and convalescent serum specimens were tested for antibodies to C. pneumoniae, M. pneumoniae and Streptococcus pneumoniae. Patients were evaluated 10 to 37 days later when repeat specimens for serology, PCR and culture were obtained. For comparative purposes healthy children attending the well-child clinic had nasopharyngeal and pharyngeal swabs obtained for PCR and culture for C. pneumoniae and M. pneumoniae.. Between February, 1996, and December, 1997, we enrolled 174 patients, 168 of whom fulfilled protocol criteria for evaluation. There were 55% males and 63% were <5 years of age. All blood cultures were sterile and there was no correlation between the white blood cell and differential counts and etiology of pneumonia. Etiologic agents were identified in 73 (43%) of 168 patients. Infection was attributed to M. pneumoniae in 7% (12 of 168), C. pneumoniae in 6% (10 of 168), S. pneumoniae in 27% (35 of 129) and viruses in 20% (31 of 157). None of the swab specimens from 75 healthy control children was positive for C. pneumoniae or M. pneumoniae. Clinical response to therapy was similar for the three antibiotic regimens evaluated, including those with infection attributed to bacterial agents.. Although a possible microbial etiology was identified in 43% of the evaluable patients, clinical findings and results of blood cultures, chest radiographs and white blood cell and differential counts did not distinguish patients with a defined etiology from those without a known cause for pneumonia. There were no differences in the clinical responses of patients to the antimicrobial regimens studied.

Topics: Adolescent; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Antibodies, Bacterial; Antibodies, Viral; Azithromycin; Child; Child, Preschool; Community-Acquired Infections; Drug Therapy, Combination; Erythromycin; Humans; Infant; Nasopharynx; Outpatient Clinics, Hospital; Pneumonia, Bacterial; Pneumonia, Viral; Prospective Studies

Chloroquine and azithromycin were developed in combination for the preventive treatment of malaria in pregnancy, and more recently were proposed as coronavirus disease 2019 (COVID-19) treatment options. Billions of doses of chloroquine have been administered worldwide over the past 70 years but concerns regarding cardiotoxicity, notably the risk of torsades de pointes (TdP), remain. This investigation aimed to characterize the pharmacokinetics and electrocardiographic effects of chloroquine and azithromycin observed in a large previously conducted healthy volunteer study. Healthy adult volunteers (n = 119) were randomized into 5 arms: placebo, chloroquine alone (600 mg base), or chloroquine with either 500 mg, 1,000 mg, or 1,500 mg of azithromycin all given daily for 3 days. Chloroquine and azithromycin levels, measured using liquid-chromatography tandem mass spectrometry, and electrocardiograph intervals were recorded at frequent intervals. Time-matched changes in the PR, QRS, and heart rate-corrected JT, and QT intervals were calculated and the relationship with plasma concentrations was evaluated using linear and nonlinear mixed-effects modeling. Chloroquine and azithromycin pharmacokinetics were described satisfactorily by two- and three-compartment distribution models, respectively. No drug-drug interaction between chloroquine and azithromycin was observed. Chloroquine resulted in concentration-dependent prolongation of the PR, QRS, JTc and QTc intervals with a minimal additional effect of azithromycin. QRS widening contributed ~ 28% of the observed QT prolongation. Chloroquine causes significant concentration-dependent delays in both ventricular depolarization and repolarization. Co-administration of azithromycin did not significantly increase these effects. The arrhythmogenic risk of TdP associated with chloroquine may have been substantially overestimated in studies which did not separate electrocardiograph QRS and JT prolongation.

Topics: Adult; Antimalarials; Azithromycin; Chloroquine; Coronavirus Infections; COVID-19 Drug Treatment; DNA-Binding Proteins; Electrocardiography; Healthy Volunteers; Humans; Hydroxychloroquine; Long QT Syndrome; Pandemics; Pneumonia, Viral; Torsades de Pointes

Off-label use of azithromycin, hydroxychloroquine, and ivermectin (the "COVID kit") has been suggested for COVID-19 treatment in Brazil without clinical or scientific evidence of efficacy. These drugs have known adverse drug reactions (ADR). This study aimed to analyze if the sales of drugs in the "COVID kit" are correlated to the reported number of ADR after the COVID-19 pandemic began. Data was obtained from the Brazilian Health Regulatory Agency (Anvisa) website on reported sales and ADRs for azithromycin, hydroxychloroquine, and ivermectin for all Brazilian states. The period from March 2019 to February 2020 (before the pandemic) was compared to that from March 2020 to February 2021 (during the pandemic). Trend adjustment was performed for time series data and cross-correlation analysis to investigate correlation between sales and ADR within the same month (lag 0) and in the following months (lag 1 and lag 2). Spearman's correlation coefficient was used to assess the magnitude of the correlations. After the pandemic onset, sales of all investigated drugs increased significantly (69.75% for azithromycin, 10,856,481.39% for hydroxychloroquine, and 12,291,129.32% for ivermectin). ADR levels of all medications but azithromycin were zero before the pandemic, but increased after its onset. Cross-correlation analysis was significant in lag 1 for all drugs nationwide. Spearman's correlation was moderate for azithromycin and hydroxychloroquine but absent for ivermectin. Data must be interpreted cautiously since no active search for ADR was performed. Our results show that the increased and indiscriminate use of "COVID kit" during the pandemic correlates to an increased occurrence of ADRs.

Topics: Azithromycin; Brazil; Coronavirus Infections; COVID-19 Drug Treatment; Drug-Related Side Effects and Adverse Reactions; Humans; Hydroxychloroquine; Ivermectin; Pandemics; Pneumonia, Viral

A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption

Topics: Animals; Antiviral Agents; Betacoronavirus; Chlorocebus aethiops; Cloning, Molecular; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Evaluation, Preclinical; Drug Repositioning; HEK293 Cells; Host-Pathogen Interactions; Humans; Immunity, Innate; Mass Spectrometry; Molecular Targeted Therapy; Pandemics; Pneumonia, Viral; Protein Binding; Protein Biosynthesis; Protein Domains; Protein Interaction Mapping; Protein Interaction Maps; Receptors, sigma; SARS-CoV-2; SKP Cullin F-Box Protein Ligases; Vero Cells; Viral Proteins

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Clinical Trials as Topic; Confounding Factors, Epidemiologic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Information Dissemination; Mass Media; Pandemics; Pneumonia, Viral; Research Design; SARS-CoV-2

COVID-19, also known as SARS-CoV-2, is a new emerging zoonotic corona virus of the SARS (Severe Acute Respiratory Syndrome) and the MERS (Middle East Respiratory Syndrome) family. COVID-19 originated in China and spread world-wide, resulting in the pandemic of 2020. For some reason, COVID-19 shows a considerably higher mortality rate in patients with advanced chronological age. This begs the question as to whether there is a functional association between COVID-19 infection and the process of chronological aging. Two host receptors have been proposed for COVID-19. One is CD26 and the other is ACE-2 (angiotensin-converting enzyme 2). Interestingly, both CD26 and the angiotensin system show associations with senescence. Similarly, two proposed therapeutics for the treatment of COVID-19 infection are Azithromycin and Quercetin, both drugs with significant senolytic activity. Also, Chloroquine-related compounds inhibit the induction of the well-known senescence marker, Beta-galactosidase. Other anti-aging drugs should also be considered, such as Rapamycin and Doxycycline, as they behave as inhibitors of protein synthesis, blocking both SASP and viral replication. Therefore, we wish to speculate that the fight against COVID-19 disease should involve testing the hypothesis that senolytics and other anti-aging drugs may have a prominent role in preventing the transmission of the virus, as well as aid in its treatment. Thus, we propose that new clinical trials may be warranted, as several senolytic and anti-aging therapeutics are existing FDA-approved drugs, with excellent safety profiles, and would be readily available for drug repurposing efforts. As Azithromycin and Doxycycline are both commonly used antibiotics that inhibit viral replication and IL-6 production, we may want to consider this general class of antibiotics that functionally inhibits cellular protein synthesis as a side-effect, for the treatment and prevention of COVID-19 disease.

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Angiotensin-Converting Enzyme 2; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Dipeptidyl Peptidase 4; Humans; Hydroxychloroquine; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Quercetin; Receptors, Virus; SARS-CoV-2

Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; Prospective Studies; SARS-CoV-2

Topics: Animals; Antimalarials; Antiviral Agents; Azithromycin; Betacoronavirus; Chlorocebus aethiops; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; Pre-Exposure Prophylaxis; SARS-CoV-2; Vero Cells

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; 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

Topics: Anti-Infective Agents; Azithromycin; Betacoronavirus; Contraindications, Drug; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Electrocardiography; Humans; Hydroxychloroquine; Long QT Syndrome; Pandemics; Pneumonia, Viral; SARS-CoV-2; Torsades de Pointes

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Age Factors; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azithromycin; Bromhexine; Coronavirus Infections; COVID-19; Cytokines; Expectorants; Humans; Hydroxychloroquine; Hypertension; Inflammation; Interferon beta-1a; Interleukin-1; Interleukin-12; Interleukin-6; Lymphohistiocytosis, Hemophagocytic; Obesity; Pandemics; Pneumonia, Viral; Pulmonary Disease, Chronic Obstructive; Respiratory Distress Syndrome; Risk Factors; Smoking; Tumor Necrosis Factor-alpha

Hydroxychloroquine (HCQ) has been used for the treatment of novel coronavirus disease (COVID-19) cases. However, evidence of efficacy remains limited, and adverse events can be associated with its use. Here, we report a case of a patient with severe COVID-19 who, after being administered HCQ, exhibited a 10-fold increase in serum levels of transaminases, followed by a rapid decrease after HCQ was withdrawn. Considering the significantly increased use of HCQ during the COVID-19 pandemic, this case alerts us to the potential for HCQ to be associated with hepatotoxicity and the need to monitor liver function during HCQ therapy.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Humans; Hydroxychloroquine; Liver; Lung; Pandemics; Piperacillin, Tazobactam Drug Combination; Pneumonia, Viral; Respiration, Artificial; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2; Tomography, X-Ray Computed

The early shortage of novel coronavirus disease (COVID-19) tests in the United States led many hospitals to first screen for common respiratory pathogens, and only if this screen was negative to proceed with COVID-19 testing. We report a case of a 56-year-old woman with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) coinfection with group A

Topics: Antibodies, Monoclonal, Humanized; Azithromycin; Betacoronavirus; Ceftriaxone; Chicago; Chronic Pain; Coinfection; Coronavirus Infections; COVID-19; Extracorporeal Membrane Oxygenation; Female; Humans; Hydroxychloroquine; Hypertension; Lung; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2; Streptococcal Infections; Streptococcus pyogenes; Tomography, X-Ray Computed; Treatment Outcome

The novel severe acute respiratory syndrome-coronavirus-2 pandemic has spread to Africa, where nearly all countries have reported laboratory-confirmed cases of novel coronavirus disease (COVID-19). Although there are ongoing clinical trials of repurposed and investigational antiviral and immune-based therapies, there are as yet no scientifically proven, clinically effective pharmacological treatments for COVID-19. Among the repurposed drugs, the commonly used antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) have become the focus of global scientific, media, and political attention despite a lack of randomized clinical trials supporting their efficacy. Chloroquine has been used worldwide for about 75 years and is listed by the WHO as an essential medicine to treat malaria. Hydroxychloroquine is mainly used as a therapy for autoimmune diseases. However, the efficacy and safety of CQ/HCQ for the treatment of COVID-19 remains to be defined. Indiscriminate promotion and widespread use of CQ/HCQ have led to extensive shortages, self-treatment, and fatal overdoses. Shortages and increased market prices leave all countries vulnerable to substandard and falsified medical products, and safety issues are especially concerning for Africa because of its healthcare system limitations. Much needed in Africa is a cross-continental collaborative network for coordinated production, distribution, and post-marketing surveillance aligned to low-cost distribution of any approved COVID-19 drug; this would ideally be piggybacked on existing global aid efforts. Meanwhile, African countries should strongly consider implementing prescription monitoring schemes to ensure that any off-label CQ/HCQ use is appropriate and beneficial during this pandemic.

Topics: Antimalarials; Antirheumatic Agents; Antiviral Agents; Azithromycin; Betacoronavirus; Chloroquine; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Drug Repositioning; Humans; Hydroxychloroquine; Off-Label Use; Pandemics; Pneumonia, Viral; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Sample Size; SARS-CoV-2; Treatment Outcome; United States

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

Solid organ transplant recipients may be at a high risk for SARS-CoV-2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty-six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual-organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty-two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non-rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID-19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID-19 has the potential to severely impact solid organ transplant recipients.

Topics: Adenosine Monophosphate; Adult; Aged; Alanine; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Critical Care; Female; Hospitalization; Humans; Hydroxychloroquine; Immunosuppression Therapy; Immunosuppressive Agents; Intensive Care Units; Intubation; Male; Middle Aged; New York City; Organ Transplantation; Pandemics; Pneumonia, Viral; Respiration, Artificial; SARS-CoV-2; Steroids; Transplant Recipients; Treatment Outcome; United States

Topics: Antiviral Agents; Arrhythmias, Cardiac; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Monitoring; Electrocardiography; Female; Humans; Hydroxychloroquine; Inpatients; Intersectoral Collaboration; Male; Middle Aged; Pandemics; Pneumonia, Viral; Risk Adjustment; SARS-CoV-2; Telemedicine; Treatment Outcome; United States

Topics: Azithromycin; Betacoronavirus; Cardiovascular Diseases; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2; Torsades de Pointes

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: Antibody Formation; Antiviral Agents; Azithromycin; Betacoronavirus; Cardiovascular Diseases; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Humans; Hydroxychloroquine; Immunity, Cellular; Immunity, Herd; Immunosuppressive Agents; Pandemics; Pneumonia, Viral; SARS-CoV-2; Viral Load; Viral Vaccines

Novel coronavirus disease 2019 (COVID-19) emerged in late December 2019 in Wuhan, China. Since then, COVID-19 has become a pandemic affecting more than 4.1 million people worldwide. Patients with COVID-19 have a wide spectrum of manifestations, one being cytokine release syndrome (CRS) and its fatal correlate, secondary hemophagocytic lymphohistiocytosis (sHLH). Anti-cytokine therapy such as tocilizumab, an IL-6 receptor antagonist, is a potential treatment for COVID-19; however, data regarding the efficacy of this anti-IL-6 therapy are currently lacking. We report two cases of patients who received a diagnosis of COVID-19 complicated by CRS and were treated with tocilizumab. Both patients progressed to sHLH despite treatment with tocilizumab, and one developed viral myocarditis, challenging the safety and clinical usefulness of tocilizumab in the treatment of COVID-19-induced CRS. These cases highlight the need for clinical trials to determine optimal patient selection and timing for the use of tocilizumab during this disease process.

Topics: Adult; Aged; Anti-Infective Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Azithromycin; Betacoronavirus; C-Reactive Protein; Clinical Deterioration; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Fatal Outcome; Female; Humans; Hydroxychloroquine; Hypoxia; Lymphohistiocytosis, Hemophagocytic; Male; Myocarditis; Pandemics; Pneumonia, Viral; Respiration, Artificial; SARS-CoV-2; Shock, Septic

Human coronaviruses SARS-CoV-2 appeared at the end of 2019 and led to a pandemic with high morbidity and mortality. As there are currently no effective drugs targeting this virus, drug repurposing represents a short-term strategy to treat millions of infected patients at low costs. Hydroxychloroquine showed an antiviral effect in vitro. In vivo it showed efficacy, especially when combined with azithromycin in a preliminary clinical trial. Here we demonstrate that the combination of hydroxychloroquine and azithromycin has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.

Topics: Animals; Antiviral Agents; Azithromycin; Betacoronavirus; Cell Line; Chlorocebus aethiops; Coronavirus Infections; COVID-19; Drug Repositioning; Drug Synergism; Drug Therapy, Combination; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2; Vero Cells; Virus Replication

The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is responsible for the global coronavirus disease 2019 pandemic. Small studies have shown a potential benefit of chloroquine/hydroxychloroquine±azithromycin for the treatment of coronavirus disease 2019. Use of these medications alone, or in combination, can lead to a prolongation of the QT interval, possibly increasing the risk of Torsade de pointes and sudden cardiac death.. Hospitalized patients treated with chloroquine/hydroxychloroquine±azithromycin from March 1 to the 23 at 3 hospitals within the Northwell Health system were included in this prospective, observational study. Serial assessments of the QT interval were performed. The primary outcome was QT prolongation resulting in Torsade de pointes. Secondary outcomes included QT prolongation, the need to prematurely discontinue any of the medications due to QT prolongation, and arrhythmogenic death.. Two hundred one patients were treated for coronavirus disease 2019 with chloroquine/hydroxychloroquine. Ten patients (5.0%) received chloroquine, 191 (95.0%) received hydroxychloroquine, and 119 (59.2%) also received azithromycin. The primary outcome of torsade de pointes was not observed in the entire population. Baseline corrected QT interval intervals did not differ between patients treated with chloroquine/hydroxychloroquine (monotherapy group) versus those treated with combination group (chloroquine/hydroxychloroquine and azithromycin; 440.6±24.9 versus 439.9±24.7 ms,. In the largest reported cohort of coronavirus disease 2019 patients to date treated with chloroquine/hydroxychloroquine±azithromycin, no instances of Torsade de pointes, or arrhythmogenic death were reported. Although use of these medications resulted in QT prolongation, clinicians seldomly needed to discontinue therapy. Further study of the need for QT interval monitoring is needed before final recommendations can be made.

Topics: Anti-Bacterial Agents; Antimalarials; Arrhythmias, Cardiac; Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Electrocardiography; Follow-Up Studies; Humans; Hydroxychloroquine; Incidence; Pandemics; Pneumonia, Viral; Prospective Studies; Risk Factors; SARS-CoV-2; United States

Topics: Adult; Azithromycin; Betacoronavirus; Clinical Trials as Topic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Data Accuracy; Drug Synergism; Drug Therapy, Combination; France; Humans; Hydroxychloroquine; Middle Aged; Pandemics; Pneumonia, Viral; Research Design; SARS-CoV-2

Topics: Azithromycin; Chloroquine; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Humans; Hydroxychloroquine; Long QT Syndrome; Mental Disorders; Pandemics; Pneumonia, Viral; Risk Factors

In France, the epidemic phase of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in February 2020 and resulted in the implementation of emergency measures and a degradation in the organization of neuromuscular reference centers. In this special context, the French Rare Health Care for Neuromuscular Diseases Network (FILNEMUS) has established guidance in an attempt to homogenize the management of neuromuscular (NM) patients within the French territory. Hospitalization should be reserved for emergencies, the conduct of treatments that cannot be postponed, check-ups for which the diagnostic delay may result in a loss of survival chance, and cardiorespiratory assessments for which the delay could be detrimental to the patient. A national strategy was adopted during a period of 1 to 2months concerning treatments usually administered in hospitalization. NM patients treated with steroid/immunosuppressants for a dysimmune pathology should continue all of their treatments in the absence of any manifestations suggestive of COVID-19. A frequently asked questions (FAQ) sheet has been compiled and updated on the FILNEMUS website. Various support systems for self-rehabilitation and guided exercises have been also provided on the website. In the context of NM diseases, particular attention must be paid to two experimental COVID-19 treatments, hydroxycholoroquine and azithromycin: risk of exacerbation of myasthenia gravis and QT prolongation in patients with pre-existing cardiac involvement. The unfavorable emergency context related to COVID-19 may specially affect the potential for intensive care admission (ICU) for people with NMD. In order to preserve the fairest medical decision, a multidisciplinary working group has listed the neuromuscular diseases with a good prognosis, usually eligible for resuscitation admission in ICU and, for other NM conditions, the positive criteria suggesting a good prognosis. Adaptation of the use of noninvasive ventilation (NIV) make it possible to limit nebulization and continue using NIV in ventilator-dependent patients.

Topics: alpha-Glucosidases; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Antimalarials; Azithromycin; Betacoronavirus; Cardiorespiratory Fitness; Coronavirus Infections; COVID-19; Emergency Treatment; France; Glycogen Storage Disease Type II; Hospitalization; Humans; Hydroxychloroquine; Immune System Diseases; Immunoglobulins, Intravenous; Immunosuppressive Agents; Muscular Atrophy, Spinal; Neuromuscular Diseases; Oligonucleotides; Pandemics; Physical Therapy Modalities; Pneumonia, Viral; Prognosis; RNA, Small Interfering; SARS-CoV-2; Steroids; Withholding Treatment

Topics: Antiviral Agents; Arrhythmias, Cardiac; Azithromycin; Cardiotoxicity; Chloroquine; Coronavirus Infections; COVID-19; Dehydration; Drug Interactions; Electrocardiography; Humans; Hydroxychloroquine; Long QT Syndrome; Pandemics; Pneumonia, Viral; Risk Assessment; Water-Electrolyte Imbalance

The first case of novel coronavirus disease (COVID-19) in the Dominican Republic coincided with a period of political crisis. Distrust in governmental institutions shaped the critical phase of early response. Having a weak public health infrastructure and a lack of public trust, the Ministry of Health (MoH) began the fight against COVID-19 with a losing streak. Within 45 days of the first reported case, the political crisis and turmoil caused by "fake news" are limiting the capacity and success of the MoH response to the pandemic.

Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Azithromycin; Betacoronavirus; Civil Disorders; Coronavirus Infections; COVID-19; Dissent and Disputes; Dominican Republic; Drug Repositioning; Humans; Hydroxychloroquine; Ivermectin; Pandemics; Pneumonia, Viral; Politics; Public Health; SARS-CoV-2; Social Media; Trust

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Betacoronavirus; Comorbidity; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Immunity, Innate; Pandemics; Pneumonia, Viral; Risk Factors; SARS-CoV-2; Steroids; Treatment Outcome

Azithromycin has been shown to have a clinical efficacy against severe acute respiratory syndrome coronavirus 2; ivermectin has also demonstrated a remarkable experimental efficacy with a potential to be used for Coronavirus disease 2019. Further, BCG vaccination is being considered for clinical trials aiming to test its potential for lowering COVID-19 morbidity and mortality. This article illustrates some structural and functional relationships that may gather these drugs and the author, basing on a combined pathophysiological and pharmacological approach, recommends the FDA-approved antidiarrhea drug; nitazoxanide, which has been previously suggested but unfortunately widely ignored, to be tested in combination with azithromycin for their potential activity against SARS CoV-2, soonest. The author also recommends testing their combined administration as early during the clinical course of COVID-19 as possible. Further, basing on the same represented concept, the author suggests more trials for interferons to be tested against SARS CoV-2, especially in severe and critical COVID-19 cases.

Topics: Antiparasitic Agents; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Humans; Nitro Compounds; Pandemics; Pneumonia, Viral; SARS-CoV-2; Thiazoles

Topics: Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2

Topics: Anemia, Hemolytic, Autoimmune; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Humans; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tomography, X-Ray Computed

Topics: Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Betacoronavirus; C-Reactive Protein; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Disease Progression; Enzyme Inhibitors; Female; Hospitalization; Humans; Hydroxychloroquine; Intensive Care Units; Interleukin 1 Receptor Antagonist Protein; Lung; Male; Middle Aged; Pandemics; Pneumonia, Viral; Respiratory Distress Syndrome; SARS-CoV-2; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome

Since December 2019, coronavirus disease (COVID-19) has been increasingly spreading from its origin in Wuhan, China to many countries around the world eventuating in morbidity and mortality affecting millions of people. This pandemic has proven to be a challenge given that there is no immediate cure, no vaccine is currently available and medications or treatments being used are still undergoing clinical trials. There have already been examples of self-medication and overdose. Clearly, there is a need to further define the efficacy of treatments used in the management of COVID-19. This evidence needs to be backed by large randomised-controlled clinical trials. In the meantime, there will no doubt be further off-label use of these medications by patients and practitioners and possibly related toxicity.

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Disease-Free Survival; Female; Follow-Up Studies; Hematologic Neoplasms; Humans; Hydroxychloroquine; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Survival Rate

Topics: Adenosine Monophosphate; Alanine; Anti-Infective Agents; Azithromycin; Betacoronavirus; Controlled Clinical Trials as Topic; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Humans; Hydroxychloroquine; Observational Studies as Topic; Pandemics; Pneumonia, Viral; Research Design; SARS-CoV-2

A recent report identified significant reductions or disappearance of viral load in COVID-19 patients given a combination of hydroxychloroquine and azithromycin. The present communication discusses some common pharmacokinetic properties of these two drugs that may be linked to a potential underlying mechanism of action for these antiviral effects. The physicochemical properties of both hydroxychloroquine and azithromycin are consistent with particularly high affinity for the intracellular lysosomal space, which has been implicated as a target site for antiviral activity. The properties of both drugs predict dramatic accumulation in lysosomes, with calculated lysosomal drug concentrations that exceed cytosolic and extracellular concentrations by more than 50 000-fold. These predictions are consistent with previously reported experimentally measured cellular and extracellular concentrations of azithromycin. This is also reflected in the very large volumes of distribution of these drugs, which are among the highest of all drugs currently in use. The combination of hydroxychloroquine and azithromycin produces very high local concentrations in lysosomes. The clinical significance of this observation is unclear; however, the magnitude of this mechanism of drug accumulation via ion-trapping in lysosomes could be an important factor for the pharmacodynamic effects of this drug combination.

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Hydroxychloroquine; Lysosomes; Pandemics; Pneumonia, Viral; SARS-CoV-2; Viral Load

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Fatal Outcome; Female; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; Radiography; SARS-CoV-2; Tomography, X-Ray Computed; Virus Activation; Virus Latency

Hydroxychloroquine, with or without azithromycin, has been considered as a possible therapeutic agent for patients with coronavirus disease 2019 (COVID-19). However, there are limited data on efficacy and associated adverse events.. To describe the association between use of hydroxychloroquine, with or without azithromycin, and clinical outcomes among hospital inpatients diagnosed with COVID-19.. Retrospective multicenter cohort study of patients from a random sample of all admitted patients with laboratory-confirmed COVID-19 in 25 hospitals, representing 88.2% of patients with COVID-19 in the New York metropolitan region. Eligible patients were admitted for at least 24 hours between March 15 and 28, 2020. Medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events were abstracted from medical records. The date of final follow-up was April 24, 2020.. Receipt of both hydroxychloroquine and azithromycin, hydroxychloroquine alone, azithromycin alone, or neither.. Primary outcome was in-hospital mortality. Secondary outcomes were cardiac arrest and abnormal electrocardiogram findings (arrhythmia or QT prolongation).. Among 1438 hospitalized patients with a diagnosis of COVID-19 (858 [59.7%] male, median age, 63 years), those receiving hydroxychloroquine, azithromycin, or both were more likely than those not receiving either drug to have diabetes, respiratory rate >22/min, abnormal chest imaging findings, O2 saturation lower than 90%, and aspartate aminotransferase greater than 40 U/L. Overall in-hospital mortality was 20.3% (95% CI, 18.2%-22.4%). The probability of death for patients receiving hydroxychloroquine + azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine + azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]). In logistic models, compared with patients receiving neither drug cardiac arrest was significantly more likely in patients receiving hydroxychloroquine + azithromycin (adjusted OR, 2.13 [95% CI, 1.12-4.05]), but not hydroxychloroquine alone (adjusted OR, 1.91 [95% CI, 0.96-3.81]) or azithromycin alone (adjusted OR, 0.64 [95% CI, 0.27-1.56]), . In adjusted logistic regression models, there were no significant differences in the relative likelihood of abnormal electrocardiogram findings.. Among patients hospitalized in metropolitan New York with COVID-19, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. However, the interpretation of these findings may be limited by the observational design.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Arrhythmias, Cardiac; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Female; Heart Arrest; Hospital Mortality; Hospitalization; Humans; Hydroxychloroquine; Logistic Models; Male; Middle Aged; New York; Pandemics; Pneumonia, Viral; Proportional Hazards Models; Retrospective Studies; SARS-CoV-2; Young Adult

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

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

The emergence of SARS-coronavirus-2 (SARS-CoV-2) has led to a global pandemic disease referred to as coronavirus disease 19 (COVID-19). Hydroxychloroquine (CLQ-OH)/azithromycin (ATM) combination therapy is currently being tested for the treatment of COVID-19, with promising results. However, the molecular mechanism of action of this combination is not yet established. Using molecular dynamics (MD) simulations, this study shows that the drugs act in synergy to prevent any close contact between the virus and the plasma membrane of host cells. Unexpected molecular similarity is shown between ATM and the sugar moiety of GM1, a lipid raft ganglioside acting as a host attachment cofactor for respiratory viruses. Due to this mimicry, ATM interacts with the ganglioside-binding domain of SARS-CoV-2 spike protein. This binding site shared by ATM and GM1 displays a conserved amino acid triad Q-134/F-135/N-137 located at the tip of the spike protein. CLQ-OH molecules are shown to saturate virus attachment sites on gangliosides in the vicinity of the primary coronavirus receptor, angiotensin-converting enzyme-2 (ACE-2). Taken together, these data show that ATM is directed against the virus, whereas CLQ-OH is directed against cellular attachment cofactors. We conclude that both drugs act as competitive inhibitors of SARS-CoV-2 attachment to the host-cell membrane. This is consistent with a synergistic antiviral mechanism at the plasma membrane level, where therapeutic intervention is likely to be most efficient. This molecular mechanism may explain the beneficial effects of CLQ-OH/ATM combination therapy in patients with COVID-19. Incidentally, the data also indicate that the conserved Q-134/F-135/N-137 triad could be considered as a target for vaccine strategies.

Topics: Amino Acid Sequence; Angiotensin-Converting Enzyme 2; Antiviral Agents; Azithromycin; Betacoronavirus; Binding Sites; Coronavirus Infections; COVID-19; Drug Synergism; G(M1) Ganglioside; Gene Expression; Host-Pathogen Interactions; Humans; Hydroxychloroquine; Kinetics; Molecular Docking Simulation; Molecular Dynamics Simulation; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; SARS-CoV-2; Sequence Alignment; Sequence Homology, Amino Acid; Spike Glycoprotein, Coronavirus; Thermodynamics; Virus Attachment

Topics: Azithromycin; Betacoronavirus; Clinical Trials as Topic; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Humans; Hydroxychloroquine; Models, Biological; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome; Viral Load

Limited data are available on the clinical presentation and outcomes of coronavirus disease (COVID-19) patients in the United States hospitalized under normal-caseload or nonsurge conditions. We retrospectively studied 72 consecutive adult patients hospitalized with COVID-19 in 2 hospitals in the San Francisco Bay area, California, USA, during March 13-April 11, 2020. The death rate for all hospitalized COVID-19 patients was 8.3%, and median length of hospitalization was 7.5 days. Of the 21 (29% of total) intensive care unit patients, 3 (14.3% died); median length of intensive care unit stay was 12 days. Of the 72 patients, 43 (59.7%) had underlying cardiovascular disease and 19 (26.4%) had underlying pulmonary disease. In this study, death rates were lower than those reported from regions of the United States experiencing a high volume of COVID-19 patients.

Topics: Adenosine Monophosphate; Aged; Aged, 80 and over; Alanine; Asthma; Azithromycin; Betacoronavirus; California; Clinical Laboratory Techniques; Comorbidity; Coronavirus Infections; COVID-19; COVID-19 Testing; Diabetes Mellitus; Female; Humans; Hyperlipidemias; Hypertension; Intensive Care Units; Length of Stay; Male; Pandemics; Pneumonia, Viral; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2; Severity of Illness Index; Survival Analysis; Tomography, X-Ray Computed

There is no known effective therapy for patients with coronavirus disease 2019 (COVID-19). Initial reports suggesting the potential benefit of hydroxychloroquine/azithromycin (HY/AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns about the potential risk of QT interval prolongation and induction of torsade de pointes (TdP).. The purpose of this study was to assess the change in corrected QT (QTc) interval and arrhythmic events in patients with COVID-19 treated with HY/AZ.. This is a retrospective study of 251 patients from 2 centers who were diagnosed with COVID-19 and treated with HY/AZ. We reviewed electrocardiographic tracings from baseline and until 3 days after the completion of therapy to determine the progression of QTc interval and the incidence of arrhythmia and mortality.. The QTc interval prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc interval prolongation to >500 ms, a known marker of high risk of TdP, had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc interval of patients exhibiting extreme QTc interval prolongation was normal.. The combination of HY/AZ significantly prolongs the QTc interval in patients with COVID-19. This prolongation may be responsible for life-threatening arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in light of its unproven efficacy. Strict QTc interval monitoring should be performed if the regimen is given.

Topics: Aged; Anti-Bacterial Agents; Antimalarials; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Female; Humans; Hydroxychloroquine; Incidence; Long QT Syndrome; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Torsades de Pointes

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Diabetes Mellitus; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Hydroxychloroquine; Male; Methemoglobinemia; Middle Aged; Obesity, Morbid; Pandemics; Pneumonia, Viral; SARS-CoV-2

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Antimalarials; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Humans; Hydroxychloroquine; Male; Meningoencephalitis; Pandemics; Pneumonia, Viral; SARS-CoV-2

Outbreak of the new type coronavirus infection, known as coronavirus infection 2019 (COVID-19), has begun in December 2019, in Wuhan, China. As of today, 3 April 2020, 972,640 people affected and 50,325 people died from Severe Acute Respiratory Syndrome-Coronavirus 2. There is not any standard treatment for coronavirus infection 2019; however, there are promising data for hydroxychloroquine and some anti-retroviral drugs. Programmed death-1 (PD-1)/programmed death ligand-1 (PDL-1) pathway is an important target for the cancer immunotherapy. However, there is a robust pre-clinical and clinical data regarding inhibitor effect of this pathway on the acute or chronic viral infections. Thus, blockade of this pathway may lead to an anti-viral effect and decrease viral load. Here, we report the clinical course of coronavirus infection 2019 infection of a patient in whom older aged, having multiple co-morbidities, and taking nivolumab for metastatic malignant melanoma. In contrast to her older age, comorbidities, and cancer diagnosis, she was in a good condition, and there was also no pneumonia finding. We think that this good clinical course of coronavirus infection 2019 infection may be related to blockade of PD-1/PDL-1 pathway with nivolumab. It is impossible to say that blockade of PD-1/PDL-1pathway is a treatment option for COVID-19; however, we want to share our experience.

Topics: Aged; Antineoplastic Agents, Immunological; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Humans; Hydroxychloroquine; Lung Neoplasms; Melanoma; Multiple Chronic Conditions; Nivolumab; Oseltamivir; Pandemics; Pneumonia, Viral; Programmed Cell Death 1 Receptor; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome

Topics: Adult; Aged; Anti-Bacterial Agents; Antimalarials; Astringents; Azithromycin; Betacoronavirus; Colitis; Coronavirus Infections; COVID-19; Humans; Hydroxychloroquine; Male; Middle Aged; Pandemics; Pneumonia, Viral; Radiography, Abdominal; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome; Zinc Sulfate

Topics: Anti-Bacterial Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; Risk Assessment; SARS-CoV-2

Hydroxychloroquine and azithromycin combination therapy is often prescribed for coronavirus disease 2019 (COVID-19). Electrocardiographic (ECG) monitoring is warranted because both medications cause corrected QT-interval (QTc) prolongation. Whether QTc duration significantly varies during the day, potentially requiring multiple ECGs, remains to be established.. We performed 12‑lead ECGs and 12‑lead 24-h Holter ECG monitoring in all patients aged <80 years admitted to our medical unit for COVID-19, in oral therapy with hydroxychloroquine (200 mg, twice daily) and azithromycin (500 mg, once daily) for at least 3 days. A group of healthy individuals matched for age and sex served as control.. Out of 126 patients, 22 (median age 64, 82% men) met the inclusion criteria. ECG after therapy showed longer QTc-interval than before therapy (450 vs 426 ms, p = .02). Four patients had a QTc ≥ 480 ms: they showed higher values of aspartate aminotransferase (52 vs 30 U/L, p = .03) and alanine aminotransferase (108 vs 33 U/L, p < .01) compared with those with QTc < 480 ms. At 24-h Holter ECG monitoring, 1 COVID-19 patient and no control had ≥1 run of non-sustained ventricular tachycardia (p = .4). No patients showed "R on T" premature ventricular beats. Analysis of 24-h QTc dynamics revealed that COVID-19 patients had higher QTc values than controls, with no significant hourly variability.. Therapy with hydroxychloroquine and azithromycin prolongs QTc interval in patients with COVID-19, particularly in those with high levels of transaminases. Because QTc duration remains stable during the 24 h, multiple daily ECG are not recommendable.

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Death, Sudden, Cardiac; Drug Monitoring; Electrocardiography; Female; Hospitalization; Humans; Hydroxychloroquine; Long QT Syndrome; Male; Middle Aged; Outcome and Process Assessment, Health Care; Pandemics; Pneumonia, Viral; SARS-CoV-2

Topics: Adrenergic beta-Agonists; Aged; Anti-Infective Agents; Azithromycin; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Electrocardiography; Humans; Hydroxychloroquine; Isoproterenol; Long QT Syndrome; Male; Myocarditis; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome; Troponin I

There are no large reported series determining the Covid-19 cancer patient's characteristics. We determine whether differences exist in cumulative incidence and mortality of Covid-19 infection between cancer patients and general population in Madrid.. We reviewed 1069 medical records of all cancer patients admitted at Oncology department between Feb 1 and April 7, 2020. We described Covid-19 cumulative incidence, treatment outcome, mortality, and associated risk factors.. We detected 45/1069 Covid-19 diagnoses in cancer patients vs 42,450/6,662,000 in total population (p < 0.00001). Mortality rate: 19/45 cancer patients vs 5586/42,450 (p = 0.0001). Mortality was associated with older median age, adjusted by staging and histology (74 vs 63.5 years old, OR 1.06, p = 0.03). Patients who combined hydroxychloroquine and azithromycin presented 3/18 deaths, regardless of age, staging, histology, cancer treatment and comorbidities (OR 0.02, p = 0.03).. Cancer patients are vulnerable to Covid-19 with an increase in complications. Combined hydroxychloroquine and azithromycin is presented as a good treatment option.

Topics: Aged; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Female; Humans; Hydroxychloroquine; Incidence; Male; Middle Aged; Neoplasms; Pandemics; Pneumonia, Viral; Risk Factors; SARS-CoV-2; Spain; Treatment Outcome

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

More than 1.6 million Americans have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than 10 times that number carry antibodies to it. High-risk patients with progressing symptomatic disease currently have only hospitalization treatment, with its high mortality, available to them. An outpatient treatment that prevents hospitalization is desperately needed. Two candidate medications have been widely discussed: remdesivir and hydroxychloroquine (HCQ) + azithromycin (AZ). Remdesivir has shown mild effectiveness in hospitalized inpatients, but no trials in outpatients have been registered. HCQ + AZ has been widely misrepresented in both clinical reports and public media, and results of outpatient trials are not expected until September. Early outpatient illness is very different from later florid disease requiring hospitalization, and the treatments differ. Evidence about use of HCQ alone, or of HCQ + AZ in inpatients, is irrelevant with regard to the efficacy of HCQ + AZ in early high-risk outpatient disease. Five studies, including 2 controlled clinical trials, have demonstrated significant major outpatient treatment efficacy. HCQ + AZ has been used as the standard of care in more than 300,000 older adults with multiple comorbid conditions; the estimated proportion of such patients diagnosed with cardiac arrhythmia attributable to the medications is 47 per 100,000 users, among whom estimated mortality is less than 20% (9/100,000 users), as compared with the 10,000 Americans now dying each week. These medications need to be made widely available and promoted immediately for physicians to prescribe.

Topics: Aged; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Female; Humans; Hydroxychloroquine; Male; Outpatients; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome

Background Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected coronavirus disease 2019 (COVID-19). Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods and Results We analyzed a case series of COVID-19-positive/suspected patients admitted between February 1, 2020, and April 4, 2020, who were treated with azithromycin, hydroxychloroquine, or a combination of both drugs. We evaluated baseline and postmedication QT interval (corrected QT interval [QTc]; Bazett) using 12-lead ECGs. Critical QTc prolongation was defined as follows: (1) maximum QTc ≥500 ms (if QRS <120 ms) or QTc ≥550 ms (if QRS ≥120 ms) and (2) QTc increase of ≥60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Of 490 COVID-19-positive/suspected patients, 314 (64%) received either/both drugs and 98 (73 COVID-19 positive and 25 suspected) met study criteria (age, 62±17 years; 61% men). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448±29 ms and increased to 459±36 ms (

Topics: Anti-Bacterial Agents; Antimalarials; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Electrocardiography; Female; Humans; Hydroxychloroquine; Long QT Syndrome; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prognosis; Risk Factors; SARS-CoV-2

The risk of COVID-19 among people living with HIV (PLWH) is largely unknown and there have been very few reported cases in the literature. We report a case series of five PLWH with COVID-19. We identified all patients with a diagnosis of HIV who tested positive for SARS-CoV-2 at University of Chicago Medicine between March 1, 2020, and April 7, 2020. We retrospectively collected data regarding demographics, comorbidities, medications, laboratory test results, radiology results, and outcomes associated with COVID-19. All five PLWH with COVID-19 were African American; 80% (4/5) were cisgender females. The mean age of patients was 48 years old (range 38-53). The majority of patients presented with cough, fever, and shortness of breath. Three patients had diarrhea. One patient presented with predominantly cardiac symptoms. All were taking antiretroviral therapy (ART) with CD4 count >200 cells/mm

Topics: Adult; Antiretroviral Therapy, Highly Active; Azithromycin; Betacoronavirus; CD4 Lymphocyte Count; Cephalosporins; Chicago; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Female; HIV Infections; Humans; Hydroxychloroquine; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Serologic Tests; Treatment Outcome

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Betacoronavirus; Chloroquine; Combined Modality Therapy; Coronavirus Infections; COVID-19; Fatal Outcome; Female; Humans; Infant; Morocco; Multiple Organ Failure; Nasopharynx; Pandemics; Pneumonia, Viral; Respiration, Artificial; Respiratory Distress Syndrome; SARS-CoV-2; Tomography, X-Ray Computed

Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness.. In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing.. Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57-76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53-2·21), male sex (1·63, 1·07-2·48), smoking status (former smoker vs never smoked: 1·60, 1·03-2·47), number of comorbidities (two vs none: 4·50, 1·33-15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11-7·18), active cancer (progressing vs remission: 5·20, 2·77-9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79-4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07-0·84) or the US-Midwest (0·50, 0·28-0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality.. Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.. American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

Topics: Aged; Antiviral Agents; Azithromycin; Betacoronavirus; Cause of Death; Comorbidity; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Databases, Factual; Female; Humans; Hydroxychloroquine; Male; Middle Aged; Neoplasms; Pandemics; Pneumonia, Viral; Prognosis; Risk Factors; SARS-CoV-2

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

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

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; France; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2

The Coronavirus (COVID-19), (Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)) has been spreading worldwide since its first identification in China. It has been speculated that patients with comorbidities and elderly patients could be at high risk for the pandemic reasoned respiratory insufficiency and death. At first, it was thought that the patients who use immunmodulator therapy could be even at higher risks of disease complications. However, it has been also speculated about that using immunmodulators could be an advantage for the clinical prognosis. Therefore, several immunmodulators are currently being tested as potential treatment for COVID-19.. In this paper we report on a patient that has been treated with type 1 interferon for multiple sclerosis who developed COVID-19.. Despite using immunmodulator, the symptoms of the patient at hospitalization were mild and he did not show elevated D-dimer, and there was no lymphopenia. He was discharged to home-quarantine with no symptoms.. This report supports the idea of using type 1 interferon in the treatment could be effective in COVID-19 affected patients.

Topics: Adult; Anti-Bacterial Agents; Antimalarials; Azithromycin; Betacoronavirus; Coronavirus Infections; Cough; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Immunologic Factors; Interferon-beta; Length of Stay; Male; Multiple Sclerosis; Pandemics; Pneumonia, Viral; SARS-CoV-2; Severity of Illness Index; Tomography, X-Ray Computed

Topics: Arrhythmias, Cardiac; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Electrocardiography; Humans; Hydroxychloroquine; Oxygen; Pandemics; Pneumonia, Viral; SARS-CoV-2; Torsades de Pointes; Viral Load

Topics: Adult; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Antihypertensive Agents; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; Cough; COVID-19; Female; Fever; Health Personnel; Humans; Hydroxychloroquine; Hypertension; Intensive Care Units; Lung; Male; Middle Aged; Myalgia; Oseltamivir; Oxygen Inhalation Therapy; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Smoking; Tomography, X-Ray Computed; Travel; Turkey; Young Adult

Topics: Acetaminophen; Anti-Inflammatory Agents; Azithromycin; Betacoronavirus; Cohort Studies; Colchicine; Community Health Services; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Fever; Gene Expression; Humans; Immunity, Innate; Inflammasomes; Intensive Care Units; Interleukin-1; Interleukin-6; Italy; Pandemics; Pneumonia, Viral; SARS-CoV-2; Severe Acute Respiratory Syndrome; Time Factors

While the COVID-19 epidemic occurred since December 2019, as of end April 2020, no treatment has been validated or invalidated by accurate clinical trials. Use of hydroxychloroquine has been popularised on mass media and put forward as a valid treatment option without strong evidence of efficacy. Hydroxychloroquine (HCQ) has its own side effects, some of which are very serious like acute haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Side effects may be worse than the disease itself. Belgian national treatment guidelines recommend the use of HCQ in mild to severe COVID-19 disease. As opinions, politics, media and beliefs are governing COVID-19 therapy, performance of randomised controlled blinded clinical trials became difficult. Results of sound clinical trials are eagerly awaited. We report a case of acute haemolysis leading to admission in intensive care unit and renal failure in a patient with uncovered G6PD deficiency.

Topics: Aged; Azithromycin; Betacoronavirus; Blood Transfusion; Continuous Renal Replacement Therapy; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Enzyme Inhibitors; Glucosephosphate Dehydrogenase Deficiency; Haptoglobins; Hemolysis; Humans; Hydroxychloroquine; Hypoxia; Male; Nasopharynx; Pandemics; Pneumonia, Viral; Respiratory Distress Syndrome; SARS-CoV-2; Severe acute respiratory syndrome-related coronavirus

Currently there are no reported series determining the Covid-19 infected lung cancer patient´s characteristics and outcome that allow us to clarify strategies to protect our patients. In our study we determine whether exists differences in cumulative incidence and severity of Covid-19 infection between lung cancer patients visiting our Medical Oncology department and the reference population of our center (320,000 people), in the current epicenter of the pandemic in Europe (Madrid, Spain). We also describe clinical and demographic factors associated with poor prognosis and Covid-19 treatment outcomes.. We retrospectively reviewed 1878 medical records of all Covid-19 patients who were admitted at Hospital Universitario Infanta Leonor of Madrid between March 5, 2020 and April 7, 2020, in order to detect cumulative incidence of Covid-19 in lung cancer patients. We also described Covid-19 treatment outcome, mortality and associated risk factors using univariate and multivariate logistic regression analysis.. 17/1878 total diagnosis in our center had lung cancer (0.9 %) versus 1878/320,000 of the total reference population (p = 0.09). 9/17 lung cancer patients with Covid-19 diagnosis died (52.3 %) versus 192/1878 Covid-19 patients in our center (p < 0.0001). Dead lung cancer patients were elderly compared to survivors: 72 versus 64.5 years old (p = 0.12). Combined treatment with hydroxychloroquine and azithromycin improves the outcome of Covid-19 in lung cancer patients, detecting only 1/6 deaths between patients under this treatment versus others treatment, with statistical significance in the univariate and multivariate logistic regression (OR 0.04, p = 0.018).. Lung cancer patients have a higher mortality rate than general population. Combined hydroxychloroquine and azithromycin treatment seems like a good treatment option. It is important to try to minimize visits to hospitals (without removing their active treatments) in order to decrease nosocomial transmission.

Topics: Aged; Aged, 80 and over; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Cross Infection; Drug Combinations; Female; Humans; Hydroxychloroquine; Logistic Models; Lung Neoplasms; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prognosis; SARS-CoV-2; Spain

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

The pandemic caused by the SARS-COV-2 or COVID-19 virus has been a global challenge given its high rate of transmission and lack of effective therapy or vaccine. This scenario has led to the use of various drugs that have demonstrated a potential effect against the virus in vitro. However, time has not been enough to properly evaluate their clinical effectiveness. The use of chloroquine/hydroxychloroquine, azithromycin and antiviral treatment and has been proposed by various groups, supported by in-vitro studies and limited patient series, without the adequate scientific rigor that precedes drug prescription. Although it may represent the only hope for many patients, it is important to know the main adverse effects associated with the use of these drugs and to better select patients who may benefit from them.. La pandemia por el virus SARS-COV-2 causante de la enfermedad COVID-19 representa un reto mundial dada su alta tasa de transmisión y ausencia de una terapia efectiva o vacuna. Este escenario ha propiciado el uso de diversos fármacos que in vitro han demostrado un potencial efecto contra el virus. Sin embargo, el tiempo no ha sido suficiente para evaluar su efectividad clínica con el adecuado rigor científico que precede a la prescripción de medicamentos. El uso de cloroquina/hidroxicloroquina, azitromicina y esquemas antivirales ha sido propuesto por diversos grupos, apoyado por series de pacientes limitada en número. Si bien puede representar la única esperanza para muchos enfermos, es importante conocer los principales efectos adversos asociados al uso de estas drogas y seleccionar mejor a los pacientes que puedan beneficiarse de ellas. El riesgo de arritmias ventriculares incrementa tanto por el uso de fármacos como por la gravedad de la propia enfermedad viral.

Topics: Antiviral Agents; Arrhythmias, Cardiac; Azithromycin; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral

We use a mechanistic lung model to demonstrate that accumulation of chloroquine (CQ), hydroxychloroquine (HCQ), and azithromycin (AZ) in the lungs is sensitive to changes in lung pH, a parameter that can be affected in patients with coronavirus disease 2019 (COVID-19). A reduction in pH from 6.7 to 6 in the lungs, as observed in respiratory disease, led to 20-fold, 4.0-fold, and 2.7-fold increases in lung exposure of CQ, HCQ, and AZ, respectively. Simulations indicated that the relatively high concentrations of CQ and HCQ in lung tissue were sustained long after administration of the drugs had stopped. Patients with COVID-19 often present with kidney failure. Our simulations indicate that renal impairment (plus lung pH reduction) caused 30-fold, 8.0-fold, and 3.4-fold increases in lung exposures for CQ, HCQ, and AZ, respectively, with relatively small accompanying increases (20 to 30%) in systemic exposure. Although a number of different dosage regimens were assessed, the purpose of our study was not to provide recommendations for a dosing strategy, but to demonstrate the utility of a physiologically-based pharmacokinetic modeling approach to estimate lung concentrations. This, used in conjunction with robust in vitro and clinical data, can help in the assessment of COVID-19 therapeutics going forward.

Topics: Anti-Infective Agents; Antiviral Agents; Azithromycin; Betacoronavirus; Biological Availability; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Dose-Response Relationship, Drug; Drug Design; Humans; Hydrogen-Ion Concentration; Hydroxychloroquine; Lung; Metabolic Clearance Rate; Pandemics; Pneumonia, Viral; SARS-CoV-2

A 71-year old gentleman with history of arterial hypertension treated with valsartan presented on was hospitalized at the Infectious Diseases Unit, University of Bologna (Italy) for severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2) and received treatment with hydroxychloroquine 200mg bid (400 mg bid the first day), azithromycin 400 mg qd, thrombotic prophylaxis with enoxaparin 4000 UI qd and Venturi mask oxygen delivering FiO2 of 31%. The case highlights the high frequency of coagulopathy in patients with moderate to severe cases of SARS-CoV-2 associated disease (COVID-19). After one week the patient significantly improved and the daily dose of enoxaparin was reduced and definitively discontinued four days later. The case highlights the high frequency of coagulopathy in patients with moderate to severe cases of SARS-CoV-2 associated disease (COVID-19). Considering the available information we believe that LMWH may represent a promising treatment for COVID-19 but further well-designed trials are needed to address these points.

Topics: Aged; Anti-Inflammatory Agents; Anticoagulants; Antihypertensive Agents; Azithromycin; Combined Modality Therapy; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Enoxaparin; Humans; Hydroxychloroquine; Hypertension; Male; Oxygen Inhalation Therapy; Pandemics; Pneumonia, Viral; Thrombophilia; Tomography, X-Ray Computed; Valsartan

The co-administration of hydroxychloroquine with azithromycin is proposed in COVID-19 therapy. We hypothesize a new mechanism supporting the synergistic interaction between these drugs. Azithromycin is a substrate of ABCB1 (P-glycoprotein) which is localized in endosomes and lysosomes with a polarized substrate transport from the cell cytosol into the vesicle interior. SARS-CoV-2 and drugs meet in these acidic organelles and both basic drugs, which are potent lysosomotropic compounds, will become protonated and trapped within these vesicles. Consequently, their intra-vesicular concentrations can attain low micromolar effective cytotoxic concentrations on SARS-CoV-2 while concomitantly increase the intra-vesicular pH up to around neutrality. This last effect inhibits lysosomal enzyme activities responsible in virus entry and replication cycle. Based on these considerations, we hypothesize that ABCB1 could be a possible enhancer by confining azithromycin more extensively than expected when the trapping is solely dependent on the passive diffusion. This additional mechanism may therefore explain the synergistic effect when azithromycin is added to hydroxychloroquine, leading to apparently more rapid virus clearance and better clinical benefit, when compared to monotherapy with hydroxychloroquine alone.

Topics: Anti-Infective Agents; ATP Binding Cassette Transporter, Subfamily B; Azithromycin; Coronavirus Infections; COVID-19; Drug Synergism; Drug Therapy, Combination; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral

Topics: Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiviral Agents; Azithromycin; Child; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Critical Care; Humans; Immunologic Factors; Pandemics; Pneumonia, Viral

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Pandemics; Pharmacists; Pneumonia, Viral; SARS-CoV-2

Topics: Aged; Anti-Bacterial Agents; Anticoagulants; Antimalarials; Azithromycin; Betacoronavirus; Ceftriaxone; Cerebral Infarction; Coronavirus Infections; COVID-19; Humans; Hydroxychloroquine; Male; Pandemics; Pneumonia, Viral; SARS-CoV-2

The Food and Drug Administration (FDA) warned against the use of Hydroxychloroquine or chloroquine for Covid-19 outside of a hospital or a clinical trial setting due to the risk of QT interval prolongation, ventricular tachycardia and the increased risk of these complications when combined with some antibiotics such as azithromycin. Several studies have reported no benefit of Hydroxychloroquine or chloroquine, when used alone or with a macrolide in COVID-19 hospitalized patients. Despite these warnings, in several developing countries the official guidelines for treatment of Covid-19 patients at the primary care level recommend Hydroxychloroquine and azithromycin, among other treatments, as the first-choice for mild symptomatic Covid-19 patients, asymptomatic contacts or for prophylaxis. In our opinion there is a primum non nocere dilemma during this Covid-19 pandemic. In order to solve this bioethical problem, we strongly recommend that a randomized controlled trial in a primary care setting be carried out as a matter of urgency in these areas of the world.

Topics: Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Developing Countries; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; Primary Health Care; SARS-CoV-2

Topics: Adult; Anti-Bacterial Agents; Anticoagulants; Anticonvulsants; Azithromycin; Betacoronavirus; Brain Edema; Brain Infarction; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Testing; Decompression, Surgical; Enzyme Inhibitors; Epilepsy; Glucocorticoids; Humans; Hydroxychloroquine; Intracranial Hemorrhages; Lung; Magnetic Resonance Imaging; Male; Nephrosis; Olfaction Disorders; Pandemics; Pneumonia, Viral; Prednisone; Pregnenediones; SARS-CoV-2; Seizures; Severity of Illness Index; Sinus Thrombosis, Intracranial; Tomography, X-Ray Computed

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Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Betacoronavirus; Bronchoalveolar Lavage Fluid; Coronavirus Infections; COVID-19; Female; Humans; Lincomycin; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prospective Studies; Risk Factors; SARS-CoV-2

Topics: Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2; United States

Topics: Acetates; Adrenergic beta-2 Receptor Antagonists; Amoxicillin-Potassium Clavulanate Combination; Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Azithromycin; Betacoronavirus; Budesonide; Convalescence; Coronavirus Infections; COVID-19; Cyclopropanes; Eosinophils; Female; Humans; Hydroxychloroquine; Ipratropium; Male; Middle Aged; Pandemics; Pneumonia, Viral; Quinolines; SARS-CoV-2; Sulfides; 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: Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Anticoagulants; Antimalarials; Antiviral Agents; Azithromycin; Betacoronavirus; Biomedical Research; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; COVID-19 Testing; Data Accuracy; Device Approval; Diagnostic Test Approval; Drug and Narcotic Control; Drug Approval; European Union; Glucocorticoids; Heparin; Humans; Immunization, Passive; Medical Device Legislation; Pandemics; Personal Protective Equipment; Pneumonia, Viral; SARS-CoV-2; Ventilators, Mechanical

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

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) caused a pandemic that first discovered in Wuhan, China. While 10% of the patients have asymptomatic infection, 15-20% have lung involvement, 5-10% have multiple organ failure, and macrophage activation syndrome. Chronic respiratory diseases, diabetes mellitus, hypertension, and cancer are risk factors for mortality. Prognosis or optimal treatment strategy for renal transplant recipients in SARS-CoV-2 infection is still unknown. Besides fatal cases, there were also milder case reports. In addition, COVID-19 treatment and the maintenance immunosuppression strategy is still under debate. Antiviral therapies and drug interactions are special topics for these patients. To the best of our knowledge, favipiravir and anti-cytokine treatments have not been previously reported in a kidney transplant recipient with SARS-CoV-2 infection before. We report a case of SARS-CoV-2 infection in a kidney transplant recipient with fatal outcomes.

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Clinical Deterioration; Coronavirus Infections; COVID-19; Fatal Outcome; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Multiple Organ Failure; Pandemics; Pneumonia, Viral; Respiration, Artificial; SARS-CoV-2; Tomography, X-Ray Computed

There have been controversies on the prophylactic effect of hydroxychloroquine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We describe a patient, 60-year old Korean woman, with coronavirus disease 2019 (COVID-19) who had been taking hydroxychloroquine for 6 months. Her serum and saliva concentrations of hydroxychloroquine were 280 μg/L and 4,890 μg/L, respectively. The present case raises concerns on hydroxychloroquine's role as a prophylactic agent for COVID-19.

Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Humans; Hydroxychloroquine; Middle Aged; Pandemics; Pneumonia, Viral; Primary Prevention; SARS-CoV-2

Invasive aspergillosis is a well-known complication of severe influenza pneumonia with acute respiratory distress syndrome (ARDS). However, recent studies are reporting emergence of aspergillosis in severe COVID-19 pneumonia, named as COVID-19-associated pulmonary aspergillosis (CAPA).. A retrospective observational study was conducted in patients with severe COVID-19 pneumonia from February 2020 to April 2020. Patients ≥18 years of age with clinical features and abnormal chest imaging with confirmed COVID-19 by RT-PCR for SARS-CoV-2 were included. CAPA was diagnosed based on clinical parameters, radiological findings and mycological data. Data were recorded on a structured proforma, and descriptive analysis was performed using Stata ver 12.1.. A total of 147 patients with confirmed COVID-19 and 23 (15.6%) patients requiring ICU admission were identified. Aspergillus species were isolated from tracheal aspirates of nine (39.1%) patients, and of these, five patients (21.7%) were diagnosed with CAPA and four (17.4%) had Aspergillus colonisation. The mean age of patients with CAPA was 69 years (Median age: 71, IQR: 24, Range: 51-85), and 3/5 patients were male. The most frequent co-morbid was diabetes mellitus (4/5). The overall fatality rate of COVID-19 patients with aspergillosis was 44% (4/9). The cause of death was ARDS in all three patients with CAPA, and the median length of stay was 16 days (IQR: 10; Range 6-35 days).. This study highlights the need for comparative studies to establish whether there is an association of aspergillosis and COVID-19 and the need for screening for fungal infections in severe COVID-19 patients with certain risk factors.

Topics: Aged; Aged, 80 and over; Azithromycin; Coronavirus Infections; COVID-19; Diabetes Complications; Female; Humans; Hydroxychloroquine; Invasive Pulmonary Aspergillosis; Male; Middle Aged; Nasopharynx; Pakistan; Pandemics; Pneumonia, Viral; Respiratory Distress Syndrome; Retrospective Studies; Risk Factors

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: Anti-Infective Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Dimensional Measurement Accuracy; Drug Monitoring; Electrocardiography; Female; Humans; Hydroxychloroquine; Long QT Syndrome; Male; Middle Aged; Outcome Assessment, Health Care; Pandemics; Pneumonia, Viral; SARS-CoV-2; Torsades de Pointes

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Betacoronavirus; Ceftriaxone; Coronavirus Infections; COVID-19; Diagnosis, Differential; Erythema Multiforme; Humans; Inflammation; Male; Pandemics; Pneumonia, Viral; 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

There is limited data regarding the electrophysiological abnormalities and arrhythmias in children with COVID-19, including those associated with treatment using potentially proarrhythmic hydroxychloroquine (HCQ) and azithromycin (AZN).. To describe the electrophysiologic findings and arrhythmias associated with pediatric COVID-19 and its treatment.. A single-center retrospective chart review was undertaken and included all patients with (1) symptoms of COVID-19 and (2) PCR-positive nasopharyngeal swabs for SARS-CoV-2 who were placed on continuous telemetry for the duration of their hospitalization during March through May, 2020.. Thirty-six patients were included in the study. Significant arrhythmias were found in 6 (nonsustained ventricular tachycardia in 5 and sustained atrial tachycardia in 1). All were self-resolving and half prompted prophylactic antiarrhythmic therapy. Patients with significant arrhythmias were likely to have noncardiac comorbidities (4/6), but these were not more common than in patients without arrhythmias (20/30, P = 1). The use of HCQ was associated with statistically significant QTc prolongation (413 ± 19 ms vs 425 ± 16 ms, P =.005). QTc was not statistically different in patients with and without arrhythmias (425 ± 15 ms vs 425 ± 15 ms, P = 1).. In pediatric patients with PCR-positive active COVID-19 infection, significant arrhythmias are infrequent, but are more common than expected in a general pediatric population. Comorbidities are not more common in patients with arrhythmias than in patients without arrhythmias. COVID-19 treatment using HCQ is associated with QTc prolongation but was not associated with arrhythmias in pediatric patients.

Topics: Anti-Infective Agents; Arrhythmias, Cardiac; Azithromycin; Betacoronavirus; Child; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Electrocardiography; Female; Humans; Hydroxychloroquine; Incidence; Long QT Syndrome; Male; New York City; Outcome and Process Assessment, Health Care; Pandemics; Pneumonia, Viral; Retrospective Studies; Risk Factors; SARS-CoV-2

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

The United States is in an acceleration phase of the COVID-19 pandemic. Currently there is no known effective therapy or vaccine for treatment of SARS-CoV-2, highlighting urgency around identifying effective therapies.. The purpose of this study was to evaluate the role of hydroxychloroquine therapy alone and in combination with azithromycin in hospitalized patients positive for COVID-19.. Multi-center retrospective observational study.. The Henry Ford Health System (HFHS) in Southeast Michigan: large six hospital integrated health system; the largest of hospitals is an 802-bed quaternary academic teaching hospital in urban Detroit, Michigan.. Consecutive patients hospitalized with a COVID-related admission in the health system from March 10, 2020 to May 2, 2020 were included. Only the first admission was included for patients with multiple admissions. All patients evaluated were 18 years of age and older and were treated as inpatients for at least 48h unless expired within 24h.. Receipt of hydroxychloroquine alone, hydroxychloroquine in combination with azithromycin, azithromycin alone, or neither.. The primary outcome was in-hospital mortality.. Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4-10 days), median age was 64 years (IQR:53-76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3-53). Overall in-hospital mortality was 18.1% (95% CI:16.6%-19.7%); by treatment: hydroxychloroquine+azithromycin, 157/783 (20.1% [95% CI: 17.3%-23.0%]), hydroxychloroquine alone, 162/1202 (13.5% [95% CI: 11.6%-15.5%]), azithromycin alone, 33/147 (22.4% [95% CI: 16.0%-30.1%]), and neither drug, 108/409 (26.4% [95% CI: 22.2%-31.0%]). Primary cause of mortality was respiratory failure (88%); no patient had documented torsades de pointes. From Cox regression modeling, predictors of mortality were age>65 years (HR:2.6 [95% CI:1.9-3.3]), white race (HR:1.7 [95% CI:1.4-2.1]), CKD (HR:1.7 [95%CI:1.4-2.1]), reduced O2 saturation level on admission (HR:1.5 [95%CI:1.1-2.1]), and ventilator use during admission (HR: 2.2 [95%CI:1.4-3.3]). Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine+azithromycin 71% compared to neither treatment (p<0.001).. In this multi-hospital assessment, when controlling for COVID-19 risk factors, treatment with hydroxychloroquine alone and in combination with azithromycin was associated with reduction in COVID-19 associated mortality. Prospective trials are needed to examine this impact.

Topics: Aged; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Female; Hospital Mortality; Hospitalization; Humans; Hydroxychloroquine; Inpatients; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; Risk Factors; SARS-CoV-2

Topics: Anti-Infective Agents; Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Databases, Pharmaceutical; Drug Prescriptions; Humans; Hydroxychloroquine; Outpatients; Pandemics; Pneumonia, Viral; Practice Patterns, Physicians'; Pre-Exposure Prophylaxis; Prescription Drug Monitoring Programs; SARS-CoV-2; United States

As the COVID-19 pandemic continues to claim lives across the globe, insufficient data exists regarding the optimal treatment. It is well known that patients 55 years of age or older and patients with certain chronic diseases are at higher risk of severe illness, including acute respiratory distress syndrome and death. A potentially fatal pulmonary complication of sickle cell disease, acute chest syndrome, can be precipitated by acute infections, including respiratory viruses. We report the case of a patient with sickle cell disease (HbSC) who developed COVID-19 pneumonia and acute chest syndrome who was treated with emergent red blood cell exchange in order to avoid endotracheal intubation.

Topics: Acute Chest Syndrome; Adult; Analgesics; Anemia, Sickle Cell; Antiviral Agents; Azithromycin; Betacoronavirus; Combined Modality Therapy; Contraindications, Procedure; Coronavirus Infections; COVID-19; Erythrocyte Transfusion; Humans; Hydroxychloroquine; Intubation, Intratracheal; Male; Methylprednisolone; Oxygen Inhalation Therapy; Pandemics; Pneumonia, Viral; Respiration, Artificial; Respiratory Insufficiency; SARS-CoV-2

Topics: Anti-Bacterial Agents; Antimalarials; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Electrocardiography; Humans; Hydroxychloroquine; Long QT Syndrome; Pandemics; Pneumonia, Viral; SARS-CoV-2; Torsades de Pointes; Treatment Outcome

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

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Humans; Pancreatitis; Pandemics; Pneumonia, Viral; SARS-CoV-2; Sinusitis

Hydroxychloroquine, chloroquine, and azithromycin have been used for treatment of COVID-19, but may cause QT prolongation. Minority populations are disproportionately impacted by COVID-19. This study evaluates the risk of QT prolongation and subsequent outcomes after administration of these medications in largely underrepresented minority COVID-19 patients.. We conducted an observational study on hospitalized COVID-19 patients in the Montefiore Health System (Bronx, NY). We examined electrocardiograms (ECG) pre/post-medication initiation to evaluate QTc, HR, QRS duration, and presence of other arrhythmias.. One hundred five patients (mean age 67 years; 44.8% F) were analyzed. The median time from the first dose of any treatment to post-medication ECG was 2 days (IQR: 1-3). QTc in men increased from baseline (440 vs 455 ms, p < 0.001), as well as in women (438 vs 463 ms, p < 0.001). The proportion of patients with QT prolongation increased significantly (14.3% vs 34.3%, p < 0.001) even when adjusted for electrolyte abnormalities. The number of patients whose QTc > 500 ms was significantly increased after treatment (16.2% vs. 4.8%, p < 0.01). Patients with either QTc > 500 ms or an increase of 60 ms had a higher frequency of death (47.6% vs. 22.6%, p = 0.02) with an odds ratio of 3.1 (95% CI: 1.1-8.7). Adjusting for race/ethnicity yielded no significant associations.. Hydroxychloroquine, chloroquine, and/or azithromycin were associated with QTc prolongation but did not result in fatal arrhythmias. Our findings suggest that any harm is unlikely to outweigh potential benefits of treatment. Careful risk-benefit analyses for individual patients should guide the use of these medications. Randomized control trials are necessary to evaluate their efficacies.

Topics: Age Distribution; Aged; Aged, 80 and over; Antimalarials; Azithromycin; Chloroquine; Coronavirus Infections; COVID-19; Electrocardiography; Female; Follow-Up Studies; Hospitalization; Humans; Hydroxychloroquine; Incidence; Long QT Syndrome; Male; Middle Aged; Pandemics; Pneumonia, Viral; Risk Assessment; Sex Distribution; Urban Population

Topics: Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2

Disease progression and treatment with hydroxychloroquine and azithromycin ere associated with increased all-cause 30-day mortality in patients with cancer compared with patients either in remission or with no evidence of disease, according to data presented during a 2020 American Society of Clinical Oncology Virtual Scientific Program press briefing.

Topics: Anti-Infective Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Disease Progression; Humans; Hydroxychloroquine; Mortality; Neoplasms; Pandemics; Pneumonia, Viral; Risk Assessment; SARS-CoV-2

The clinical implications of COVID-19 in pregnancy remain unknown. While preliminary reports demonstrate that pregnant patients have a similar symptomatic presentation to the general population, the appropriate management and timing of delivery in these patients is still unclear, as pregnancy may impose additional risk factors and impede recovery in gravid patients. In this brief report, we present a case of COVID-19 in a pregnant patient with severe respiratory compromise, whose clinical status significantly improved after caesarean delivery. We also address the potential benefits of experimental therapy, including tocilizumab, a monoclonal antibody that targets interleukin-6 receptors.

Topics: Adult; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Azithromycin; Betacoronavirus; Ceftriaxone; Cesarean Section; Coronavirus Infections; COVID-19; Disease Progression; Enzyme Inhibitors; Female; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; Postpartum Period; Pregnancy; Pregnancy Complications, Infectious; SARS-CoV-2; Treatment Outcome

Primary neuroendocrine tumors of the thymus are extremely rare. In patients with advanced disease, tumor growth control, and sometimes also syndrome control are the main goals of systemic therapy. Unfortunately, no standard therapies are available in clinical practice; therefore, clinical studies are strongly recommended. Axitinib (AXI) is a tyrosine kinase inhibitor, currently under investigation in an international phase II/III trial including thymic neuroendocrine tumors. Over the past 5 months, the entire world has been facing a devastating medical emergency brought about by a pandemic due to a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China, in late 2019. Since then, health professionals have been expending all their efforts on trying to provide the best available treatments for patients involved. Patients with cancer, especially those with thoracic involvement, are at higher risk of coronavirus disease 19 (COVID-19) and its complications because of their immunosuppressive status caused by the cancer and the anticancer therapies. As it remains unclear how to optimally manage such patients, we wished to report our experience with a patient with a metastatic neuroendocrine tumor of the thymus infected with SARS-CoV-2 in the hope that it may provide some insights and reflections on the management of cancer patients during this challenging time in our history.

Topics: Aged; Axitinib; Azithromycin; Betacoronavirus; Carcinoid Tumor; Comorbidity; Coronavirus Infections; COVID-19; Humans; Hydroxychloroquine; Italy; Male; Neuroendocrine Tumors; Pandemics; Pneumonia, Viral; Protein-Tyrosine Kinases; Randomized Controlled Trials as Topic; SARS-CoV-2; Thymus Neoplasms; Tomography, X-Ray Computed; Treatment Outcome

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

In this issue of the Journal, Dr. Risch (Am J Epidemiol. 2020;189(11):1218-1226) posits that the use of a combination of hydroxychloroquine and azithromycin as an outpatient treatment for high-risk patients with coronavirus 19 should be increased as a way to help curtail the ongoing pandemic. However, a calculation error occurred in the original article, and new data about the studies cited have come to light. Peculiarities in the methods of data collection and reporting in those original sources must be considered when evaluating the evidence for or against hydroxychloroquine and azithromycin bitherapy.

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Humans; Hydroxychloroquine; Outpatients; Pandemics; Pneumonia, Viral; SARS-CoV-2

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Outpatients; Pandemics; Pneumonia, Viral; SARS-CoV-2

Hydroxychloroquine alone or in combination with azithromycin has been increasingly used for patients with coronavirus disease 2019, in both children and adults. Drugs are generally well tolerated in clinical practice; however, both can cause corrected QT prolongation. We aimed to report our experience of QT interval evaluation associated with the use of hydroxychloroquine with concurrent azithromycin among children testing positive for coronavirus disease 2019.. Our single-centre; retrospective, study evaluated children with coronavirus disease 2019 disease admitted to the Pediatric Department at Sancaktepe Training and Research Hospital Istanbul, Turkey from 10 March, 2020 to 10 April, 2020. The data including demographics, clinical symptoms, co-morbid diseases, laboratory, radiological findings as well as electrocardiographs of the patients were obtained from our records. Electrocardiograms were evaluated before, one day after and at the termination of the treatment.. 21 patients aged 9 to 18 years were evaluated. The median age was 170 months (range 112-214), 51.1% of them were girls and 48.9% were boys. Their laboratory results did not reveal any abnormalities. None of them needed intensive care. We did not detect QT prolongation during or at the termination of the treatment.. We did not detect QT prolongation during or at the termination of the treatment in our patients due to the fact that they were not severely affected by the disease. Patients were treated in our inpatient clinic and none of them required intensive care. Laboratory results were also insignificant. Furthermore, they did not need other medications.

Topics: Adolescent; Anti-Infective Agents; Azithromycin; Child; Coronavirus Infections; COVID-19; Electrocardiography; Female; Hospitalization; Humans; Hydroxychloroquine; Long QT Syndrome; Male; Outcome and Process Assessment, Health Care; Pandemics; Pneumonia, Viral; Retrospective Studies; Turkey

Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease

Topics: Animals; Azithromycin; Betacoronavirus; Chlorocebus aethiops; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytokines; Disease Models, Animal; Female; Humans; Hydroxychloroquine; In Vitro Techniques; Kinetics; Macaca fascicularis; Male; Pandemics; Pneumonia, Viral; Pre-Exposure Prophylaxis; Respiratory Mucosa; SARS-CoV-2; Time Factors; Treatment Failure; Vero Cells; Viral Load

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has caused a devastating worldwide pandemic. Hydroxychloroquine (HCQ) has in vitro activity against SARS-CoV-2, but clinical data supporting HCQ for coronavirus disease 2019 (COVID-19) are limited.. This was a retrospective cohort study of hospitalized patients with COVID-19 who received ≥1 dose of HCQ at two New York City hospitals. We measured incident Grade 3 or 4 blood count and liver test abnormalities, ventricular arrhythmias, and vomiting and diarrhea within 10 days after HCQ initiation, and the proportion of patients who completed HCQ therapy. We also describe changes in Sequential Organ Failure Assessment hypoxia scores between baseline and day 10 after HCQ initiation and in-hospital mortality.. None of the 153 hospitalized patients with COVID-19 who received HCQ developed a sustained ventricular tachyarrhythmia. Incident blood count and liver test abnormalities occurred in <15% of patients and incident vomiting or diarrhea was rare. Eighty-nine percent of patients completed their HCQ course and three patients discontinued therapy because of QT prolongation. Fifty-two percent of patients had improved hypoxia scores 10 days after starting HCQ. Thirty-one percent of patients who were receiving mechanical ventilation at the time of HCQ initiation died during their hospitalization, compared to 18% of patients who were receiving supplemental oxygen but not requiring mechanical ventilation, and 8% of patients who were not requiring supplemental oxygen. Co-administration of azithromycin was not associated with improved outcomes.. HCQ appears to be reasonably safe and tolerable in most hospitalized patients with COVID-19. However, nearly one-half of patients did not improve with this treatment, highlighting the need to evaluate HCQ and alternate therapies in randomized trials.

Topics: Adult; Aged; Azithromycin; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Female; Humans; Hydroxychloroquine; Male; Middle Aged; New York City; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Treatment Outcome

The evolving pandemic of Coronavirus Disease 2019 has posed a substantial health risk worldwide. However, there is a paucity of data regarding the clinical course and the therapeutic management of patients with chronic kidney disease and COVID-19 infection. To date, most evidence has come from renal transplantation, with about 45 patients reported thus far, and the current data from the ERA-EDTA (ERACODA) registry for transplanted patients and patients on Renal Replacement Therapy (RRT); as for those with glomerular diseases, data are lacking. Herein, we report the case of a 62-year-old patient with severe membranoproliferative glomerulonephritis who had been receiving a high burden of immunosuppression until four months before the COVID-19 infection. He developed severe disease with acute respiratory failure requiring mechanical ventilation. After treatment with hydroxychloroquine and azithromycin, despite his low chances, he gradually recovered and survived. To the best of our knowledge, this is one of the few reported patients with glomerulonephritis who had COVID-19 Besides our single case with glomerulonephritis early during the disease outbreak, the very low prevalence of COVID-19 infection in the country's transplant recipients (0.038%) and dialysis patients (0.24%) reflects the impact of the rapid implementation of social distancing rules as well as of preventive measures for disease control in the hospitals and dialysis units in our country.

Topics: Anti-Bacterial Agents; Azithromycin; Betacoronavirus; Ceftriaxone; Coronavirus Infections; COVID-19; Creatinine; Cryoglobulinemia; Cyclophosphamide; Enzyme Inhibitors; Glomerulonephritis, Membranoproliferative; Glucocorticoids; Greece; Humans; Hydroxychloroquine; Immunocompromised Host; Immunologic Factors; Kidney Failure, Chronic; Kidney Transplantation; Leukemia, Lymphocytic, Chronic, B-Cell; Lung; Male; Methylprednisolone; Middle Aged; Pandemics; Pneumonia, Viral; Renal Dialysis; Respiration, Artificial; Respiratory Insufficiency; Reverse Transcriptase Polymerase Chain Reaction; Rituximab; SARS-CoV-2; Tomography, X-Ray Computed

Coronavirus disease 19 (COVID-19) is a viral pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease started as an epidemic in China in December 2019 that later achieved a pandemic potential spreading to over 210 countries with more than 3.5 million confirmed cases and close to 250,000 deaths till date. Its symptoms most commonly include, dry cough, fever, myalgia, and fatigue. As the number of new cases keeps on rising, many patients have been documented with gastrointestinal manifestations such as diarrhoea, vomiting and abdominal pain. We report a case of a 23-year-old female who presented with the primary complaint of diarrhoea, after positive contact history with a COVID-19 patient. Key Words: SARS-CoV-2, COVID-19, Pneumonia, ARDS, Diarrhoea.

Topics: Azithromycin; Betacoronavirus; Coronavirus; Coronavirus Infections; Cough; COVID-19; Diarrhea; Female; Fever; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2; Treatment Outcome; Young Adult

Coronavirus disease (COVID-19), first reported in December 2019 in Wuhan, China, has spread all over the world in a short time and was declared as a pandemic by the World Health Organization (WHO). During COVID-19 pandemic, chest computed tomography (CT) imaging has become an important tool with high sensitivity for diagnosis due to the low positive rate of the real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Furthermore, the chest CT has played an important role in the diagnosis of underlying pulmonary lesions. In this case report, we present a patient who was admitted to the emergency department with fever, cough and left shoulder pain, and was subsequently diagnosed with both COVID-19 and pneumothorax following chest CT and RT-PCR test. Key Words: COVID-19, Coronavirus, Pneumothorax, Tomography.

Topics: Anti-Bacterial Agents; Anticoagulants; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus; Coronavirus Infections; Cough; COVID-19; Enoxaparin; Female; Fever; Humans; Hydroxychloroquine; Lung; Male; Oseltamivir; Pandemics; Pneumonia, Viral; Pneumothorax; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

The outbreak of the SARS-Cov-2 (Severe Acute Respiratory Syndrome - Coronavirus 2) viral pandemic which started at Wuhan China has spread to 200 countries and have resulted in a huge loss to mankind and the global economy. Computerised Tomographic (CT) scan may play an important role in the diagnosis and management of the COVID -19-the disease caused by the SARS-Cov-2. This modality might help in triaging this extremely contagious disease and thus help serve in reducing the outbreak. We present five cases that presented to the hospital with mild symptoms, where the CT scan findings were disproportionate to the symptoms thus leading to effective triage. This resulted in effective disposition in isolation ward and thus helped to protect the healthcare workers from contraction of the disease. This is especially important as the definitive diagnosis via RT-PCR (Reverse Transcriptase - Polymerase Chain Reaction) would take almost 24 hours in the present time in India. Key Words: CT scan, COVID- 19, Triage, SARS-Cov-2.

Topics: Azithromycin; Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; Female; Humans; Hydroxychloroquine; Male; Middle Aged; Pandemics; Pneumonia, Viral; Quarantine; SARS-CoV-2; Tomography, X-Ray Computed; Triage

Topics: Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2; United States

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

Topics: Azithromycin; Bayes Theorem; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; SARS-CoV-2

Coronavirus disease 2019 (COVID-19) is a highly transmissible viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical trials have reported improved outcomes resulting from an effective reduction or absence of viral load when patients were treated with chloroquine (CQ) or hydroxychloroquine (HCQ). In addition, the effects of these drugs were improved by simultaneous administration of azithromycin (AZM). The receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein binds to the cell surface angiotensin-converting enzyme 2 (ACE2) receptor, allowing virus entry and replication in host cells. The viral main protease (M

Topics: Amino Acid Motifs; Angiotensin-Converting Enzyme 2; Antiviral Agents; Azithromycin; Betacoronavirus; Binding Sites; Cathepsin L; Chloroquine; Coronavirus 3C Proteases; Coronavirus Infections; COVID-19; Cysteine Endopeptidases; Host-Pathogen Interactions; Humans; Hydroxychloroquine; Molecular Docking Simulation; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Binding; Protein Interaction Domains and Motifs; Protein Structure, Secondary; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Thermodynamics; Viral Nonstructural Proteins; Virus Attachment

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

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

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

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Dust; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2

Topics: Anti-Infective Agents; Arrhythmias, Cardiac; Azithromycin; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Testing; Drug-Related Side Effects and Adverse Reactions; Hospitalization; Humans; Hydroxychloroquine; Italy; Outcome Assessment, Health Care; Pandemics; Pneumonia, Viral; SARS-CoV-2; Time-to-Treatment

Topics: Antiviral Agents; Azithromycin; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Repositioning; Evidence-Based Medicine; Hemorrhagic Fever, Ebola; Humans; Hydroxychloroquine; Observational Studies as Topic; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Hearing Loss, Sensorineural; Humans; Hydroxychloroquine; Ototoxicity; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tinnitus; Vertigo

Among candidate drugs to treat coronavirus disease 2019 (COVID-19), the combination of hydroxychloroquine (HCQ) and azithromycin (AZ) has received intense worldwide attention. Even as the efficacy of this combination is under evaluation, clinicians have begun to use it largely. As these medications are known to prolong the QT interval, we analyzed serial electrocardiograms recorded in patients hospitalized for COVID-19 pneumonia and treated with HCQ + AZ. Fifty consecutive patients received the combination of HCQ (600 mg/d for 10 days) and AZ (500 mg/d on day 1 and 250 mg/d from day 2 to day 5). Twelve-lead electrocardiograms were recorded before treatment, at day 3, at day 5, and at discharge. The median age of patients was 68 years (interquartile range, 53-81 years); 28 (56%) were men. The main comorbidities were hypertension (36%; n=18) and diabetes (16%; n=8). The mean corrected QT (QTc) interval was 408 ms at baseline and increased up to 437 ms at day 3 and to 456 ms at day 5. Thirty-eight patients (76%) presented short-term modifications of the QTc duration (>30 ms). Treatment discontinuation was decided in 6 patients (12%), leading to QTc normalization in 5 of them. No deaths and no cardiac arrhythmic events were observed in this cohort. Our report confirms that a short duration treatment with HCQ + AZ modifies the QTc interval. The treatment had to be discontinued for QTc modifications in 12% of patients. Nevertheless, in inpatients hospitalized for COVID-19, we did not observe any clinically relevant consequences of these transitory modifications. In conclusion, when patients are treated with HCQ + AZ, cardiac monitoring should be regularly performed and hospital settings allow monitoring under in safe conditions.

Topics: Adult; Aged; Aged, 80 and over; Antiviral Agents; Arrhythmias, Cardiac; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Administration Schedule; Drug Therapy, Combination; Electrocardiography; Female; Humans; Hydroxychloroquine; Male; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome

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

Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern.. We explored the clinical management of inpatients with COVID-19 in Italy.. A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed.. A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%.. In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available.

Topics: Adult; Aged; Anti-Bacterial Agents; Anticoagulants; Antiviral Agents; Azithromycin; Betacoronavirus; Cannula; Cardiology; Continuous Positive Airway Pressure; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Critical Care; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Hydroxychloroquine; Intensive Care Units; Internal Medicine; Italy; Lung; Middle Aged; Noninvasive Ventilation; Pandemics; Physicians; Pneumonia, Viral; Practice Patterns, Physicians'; Protease Inhibitors; Pulmonary Medicine; Referral and Consultation; Respiration, Artificial; Respiratory Insufficiency; SARS-CoV-2; Surveys and Questionnaires; Tomography, X-Ray Computed

To assess the efficacy and safety of hydroxychloroquine with or without azithromycin) in hospitalized adult patients with COVID-19.. We utilized a hospital based prospective data registry. The primary end point was to assess the impact of hydroxychloroquine with or without azithromycin, on outcome, length of hospitalization, and time to clinical improvement. We utilized treatment effects with inverse-probability-weighting and Cox proportional hazards models. All analyses accounted for age, gender, race, severity on admission, days from symptoms onset and chronic comorbidities.. 36 patients received hydroxychloroquine and were age- and sex-matched to 72 patients with COVID-19 who received supportive care. Compared to supportive care, the use of HCQ did not shorten the time to clinical improvement (+0.23 days; 95% CI: -1.8-2.3 days) nor did it shorten the duration of hospital stay (+0.91 days; 95% CI: -1.1-2.9 days). Additionally, HCQ did not decrease the risk of COVID-19 in-hospital death (aHR 1.67; 95% CI: 0.29-9.36). Finally, we observed a slight QTc prolongation from a baseline of 444 ± 26 ms to 464 ± 32 ms (mean±SD) among patients receiving hydroxychloroquine with or without azithromycin.. This study did not yield benefits from hydroxychloroquine use in patients with COVID-19 and monitoring for adverse events is warranted. Nevertheless, the treatment was safely studied under the guidance of an antimicrobial stewardship program.

Topics: Adult; Aged; Antiviral Agents; Azithromycin; Betacoronavirus; Comorbidity; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Female; Hospitalization; Humans; Hydroxychloroquine; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prospective Studies; SARS-CoV-2

Topics: Anemia; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2

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

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

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; 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

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antimalarials; Azithromycin; Betacoronavirus; Child; Child, Preschool; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Female; Follow-Up Studies; Hospitalization; Humans; Hydroxychloroquine; Infant; Infant, Newborn; Intensive Care Units; Interleukin-6; Kaplan-Meier Estimate; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Treatment Outcome; Young Adult

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

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

Haemodialysis patients are at risk of developing severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: coronavirus disease 2019 (COVID-19). In March 2020, hydroxychloroquine (HCQ) and azithromycin (AZI) were proposed as potential treatments of COVID-19, but with warnings concerning their possible toxicity. No data are available regarding the toxicity of this treatment in haemodialysis patients.. We report the use of HCQ and AZI in a cohort of COVID-19 haemodialysis patients with focus on safety concerns.. Twenty-one patients received 200 mg HCQ thrice daily during 10 days, and AZI 500 mg on Day 1, and 250 mg on the four following days. HCQ plasma concentrations were within the recommended range (0.1-1.0 µg/mL) in all patients except one, in which maximum concentration was 1.1 µg/mL. HCQ concentration raised until the third day and remained stable thereafter. No cardiac event occurred in spite of progressive lengthening of corrected QT interval (QTc) during the treatment. One patient experienced a long QTc syndrome (QTc >500 ms) without any arrhythmia episode, although HCQ concentration was in the target range. Five (23.8%) patients experienced hypoglycaemia, a well-known HCQ side-effect. SARS-CoV-2 RNA remained detectable in nasopharyngeal swabs for a long time in haemodialysis patients (mean time 21 days).. HCQ and AZI are safe in haemodialysis patients at these doses but can lead to long QTc syndrome and hypoglycaemia. HCQ concentrations were not correlated with side effects. We recommend monitoring of the QTc length throughout treatment, as well as glycaemia. SARS-CoV-2 could persist for longer in haemodialysis patients than in the general population.

Topics: Aged; Anti-Bacterial Agents; Antimalarials; Azithromycin; Betacoronavirus; Comorbidity; Coronavirus Infections; COVID-19; Drug Tolerance; Female; France; Humans; Hydroxychloroquine; Kidney Failure, Chronic; Male; Pandemics; Pneumonia, Viral; Renal Dialysis; SARS-CoV-2

Invasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of high flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission.This was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from 10 March 2020 to 24 April 2020 with moderate-to-severe respiratory failure treated with HFNT. Primary outcome was prevention of intubation. Of the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (+13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African-American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. Saturation to fraction ratio and chest X-ray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital-associated/ventilator-associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of pneumonia was statistically higher in the progressed to intubation group. CONCLUSION: HFNT use is associated with a reduction in the rate of invasive mechanical ventilation and overall mortality in patients with COVID-19 infection.

Topics: Adrenal Cortex Hormones; Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Azithromycin; Betacoronavirus; Black or African American; Cannula; Comorbidity; Coronavirus Infections; COVID-19; Diabetes Mellitus; Female; Healthcare-Associated Pneumonia; Heart Diseases; Hispanic or Latino; Humans; Hydroxychloroquine; Hypertension; Hypoxia; Immunoglobulins, Intravenous; Immunologic Factors; Intubation, Intratracheal; Lung Diseases; Male; Middle Aged; Oxygen Inhalation Therapy; Pandemics; Philadelphia; Pneumonia, Ventilator-Associated; Pneumonia, Viral; Pulse Therapy, Drug; Renal Insufficiency, Chronic; Respiratory Insufficiency; Retrospective Studies; SARS-CoV-2; Severity of Illness Index; Smoking; White People

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

COVID-19 is characterized by fast deterioration in the mechanism of cytokine storm. Therefore, treatment with immunomodulating agents should be initiated as soon as hyperinflammation is established. Evidence for the use of tocilizumab (TCZ) in COVID-19 is emerging, but the drug in this setting is used "off label" with limited data on both effectiveness and safety. Therefore, Hospital for Infectious Diseases in Warsaw established a Standard Operating Procedure (SOP) for the use of TCZ in severe COVID-19 cases.. Here, we present a case of 27-year-old, otherwise healthy man, who was successfully treated with chloroquine, azithromycin, tocilizumab and a standard of care. Initially the magnitude of lung devastation, clinical deterioration and the need for mechanical ventilation suggested unfavorable prognosis. However, we observed complete regression in radiological changes and rapid clinical improvement. Irrespective of this, patient's serum interleukin 6 and aminotransferases remained elevated even after a month from treatment.. An overlapping effect of hyperinflammation, hypoxic organ injury and drug-related toxicity warrants a long-term follow-up for COVID-19 survivors. In addition, residual IL-6 receptors blockage may mask new infections. A standardized approach to follow-up for COVID-19 survivors is urgently needed. Current and future research should also investigate the impact of experimental therapies on lung tissue healing and regeneration, as well as long-term treatment toxicities.

Topics: Adult; Antibodies, Monoclonal, Humanized; Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytokines; Humans; Inflammation; Male; Off-Label Use; Pandemics; Pneumonia, Viral; Poland; SARS-CoV-2; Tomography, X-Ray Computed

Topics: Anti-Inflammatory Agents; Azithromycin; Betacoronavirus; Cells, Cultured; Chronic Disease; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Down-Regulation; Host-Pathogen Interactions; Humans; Interleukin-1beta; Male; Membrane Proteins; Nasal Mucosa; Pandemics; Pilot Projects; Pneumonia, Viral; Rhinitis; SARS-CoV-2; Serine Endopeptidases; Serine Proteases; Signal Transduction; Sinusitis

Topics: Azithromycin; Betacoronavirus; Bias; Cognitive Science; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2

The emergence of SARS-coronavirus-2 (SARS-CoV-2) has led to a global pandemic disease referred to as coronavirus disease 19 (COVID-19). Hydroxychloroquine (CLQ-OH)/azithromycin (ATM) combination therapy is currently being tested for the treatment of COVID-19, with promising results. However, the molecular mechanism of action of this combination is not yet established. Using molecular dynamics (MD) simulations, this study shows that the drugs act in synergy to prevent any close contact between the virus and the plasma membrane of host cells. Unexpected molecular similarity is shown between ATM and the sugar moiety of GM1, a lipid raft ganglioside acting as a host attachment cofactor for respiratory viruses. Due to this mimicry, ATM interacts with the ganglioside-binding domain of SARS-CoV-2 spike protein. This binding site shared by ATM and GM1 displays a conserved amino acid triad Q-134/F-135/N-137 located at the tip of the spike protein. CLQ-OH molecules are shown to saturate virus attachment sites on gangliosides in the vicinity of the primary coronavirus receptor, angiotensin-converting enzyme-2 (ACE-2). Taken together, these data show that ATM is directed against the virus, whereas CLQ-OH is directed against cellular attachment cofactors. We conclude that both drugs act as competitive inhibitors of SARS-CoV-2 attachment to the host-cell membrane. This is consistent with a synergistic antiviral mechanism at the plasma membrane level, where therapeutic intervention is likely to be most efficient. This molecular mechanism may explain the beneficial effects of CLQ-OH/ATM combination therapy in patients with COVID-19. Incidentally, the data also indicate that the conserved Q-134/F-135/N-137 triad could be considered as a target for vaccine strategies.

Topics: Amino Acid Sequence; Angiotensin-Converting Enzyme 2; Antiviral Agents; Azithromycin; Betacoronavirus; Binding Sites; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Synergism; Drug Therapy, Combination; G(M1) Ganglioside; Host-Pathogen Interactions; Humans; Hydroxychloroquine; Molecular Dynamics Simulation; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Binding; Protein Domains; SARS-CoV-2; Sequence Alignment; Spike Glycoprotein, Coronavirus; Virus Attachment

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

The rapid spread of the disease caused by the novel SARS-CoV-2 virus has led to the use of multiple therapeutic agents whose efficacy has not been previously demonstrated. The objective of this study was to analyze whether there is an association between the use of azithromycin and the evolution of the pulmonary disease or the time to discharge, in patients hospitalized with COVID-19.. This was an observational study on a cohort of 418 patients admitted to three regional hospitals in Catalonia, Spain. As primary outcomes, we studied the evolution of SAFI ratio (oxygen saturation/fraction of inspired oxygen) in the first 48 hours of treatment and the time to discharge. The results were compared between patients treated and untreated with the study drug through subcohort analyses matched for multiple clinical and prognostic factors, as well as through analysis of non-matched subcohorts, using Cox multivariate models adjusted for prognostic factors.. There were 239 patients treated with azithromycin. Of these, 29 patients treated with azithromycin could be matched with an equivalent number of control patients. In the analysis of these matched subcohorts, SAFI at 48h had no significant changes associated to the use of azithromycin, though azithromycin treatment was associated with a longer time to discharge (10.0 days vs 6.7 days; log rank: p = 0.039). However, in the unmatched cohorts, the increased hospital stay associated to azithromycin use, was no significant after adjustment using Multivariate Cox regression models: hazard ratio 1.45 (IC95%: 0.88-2.41; p = 0.150). This study is limited by its small sample size and its observational nature; despite the strong pairing of the matched subcohorts and the adjustment of the Cox regression for multiple factors, the results may be affected by residual confusion.. We did not find a clinical benefit associated with the use of azithromycin, in terms of lung function 48 hours after treatment or length of hospital stay.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Case-Control Studies; Coronavirus Infections; COVID-19; Female; Humans; Male; Middle Aged; Pandemics; Patient Discharge; Pneumonia, Viral

The aim of this study was to evaluate the clinical course of COVID-19 in patients who had recently undergone a cardiac procedure and were inpatients in a cardiac rehabilitation department.. All patients hospitalized from 1 February to 15 March 2020 were included in the study (n = 35; 16 men; mean age 78 years). The overall population was divided into two groups: group 1 included 10 patients who presented with a clinical picture of COVID-19 infection and were isolated, and group 2 included 25 patients who were COVID-19-negative. In group 1, nine patients were on chronic oral anticoagulant therapy and one patient was on acetylsalicylic acid (ASA) and clopidogrel. A chest computed tomography scan revealed interstitial pneumonia in all 10 patients.. During hospitalization, COVID-19 patients received azithromycin and hydroxychloroquine in addition to their ongoing therapy. Only the patient on ASA with clopidogrel therapy was transferred to the ICU for mechanical ventilation because of worsening respiratory failure, and subsequently died from cardiorespiratory arrest. All other patients on chronic anticoagulant therapy recovered and were discharged.. Our study suggests that COVID-19 patients on chronic anticoagulant therapy may have a more favorable and less complicated clinical course. Further prospective studies are warranted to confirm this preliminary observation.

Topics: Aged; Anti-Infective Agents; Anticoagulants; Azithromycin; Cardiac Surgical Procedures; Combined Modality Therapy; Coronavirus Infections; COVID-19; Female; Humans; Hydroxychloroquine; Male; Outcome and Process Assessment, Health Care; Pandemics; Platelet Aggregation Inhibitors; Pneumonia, Viral; Postoperative Complications; Tomography, X-Ray Computed

Topics: Azithromycin; Betacoronavirus; Brazil; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; Standard of Care

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

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Dioxolanes; Expectorants; Humans; Medicine, Chinese Traditional; Mucus; Oseltamivir; Pandemics; Pneumonia, Viral; Povidone; SARS-CoV-2

Topics: Azithromycin; Betacoronavirus; Cell Membrane Permeability; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Hospitalization; Humans; Hydroxychloroquine; Ionophores; Length of Stay; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Zinc Sulfate

Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias.. To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin.. This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020.. Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events.. Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes.. In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.

Topics: Aged; Anti-Bacterial Agents; Antimalarials; Azithromycin; Betacoronavirus; Cohort Studies; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Female; Hospitalization; Humans; Hydroxychloroquine; Long QT Syndrome; Male; Middle Aged; Pandemics; Pneumonia, Viral; Risk Assessment; SARS-CoV-2

Topics: Azithromycin; Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Intensive Care Units; Pandemics; Pneumonia, Viral; SARS-CoV-2

Topics: Aged; Anti-Bacterial Agents; Antimalarials; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Critical Care; Drug Therapy, Combination; Female; Humans; Hydroxychloroquine; Long QT Syndrome; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2

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

Combination therapy using chloroquine (CQ) and azithromycin (AZM) has drawn great attention due to its potential anti-viral activity against SARS-CoV-2. However, clinical trials have revealed that the co-administration of CQ and AZM resulted in severe side effects, including cardiac arrhythmia, in patients with COVID-19. To elucidate the cardiotoxicity induced by CQ and AZM, we examined the effects of these drugs based on the electrophysiological properties of human embryonic stem cellderived cardiomyocytes (hESC-CMs) using multi-electrode arrays. CQ treatment significantly increased the field potential duration, which corresponds to prolongation of the QT interval, and decreased the spike amplitude, spike slope, and conduction velocity of hESC-CMs. AZM had no significant effect on the field potentials of hESC-CMs. However, CQ in combination with AZM greatly increased the field potential duration and decreased the beat period and spike slope of hESC-CMs when compared with CQ monotherapy. In support of the clinical data suggesting the cardiovascular side effects of the combination therapy of CQ and AZM, our results suggest that AZM reinforces the cardiotoxicity induced by CQ in hESC-CMs. [BMB Reports 2020; 53(10): 545-550].

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Azithromycin; Cardiotoxicity; Cell Differentiation; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Embryonic Stem Cells; Humans; Mice; Myocytes, Cardiac; Pandemics; Pneumonia, Viral

Objectives The severe acute respiratory syndrome coronavirus 2 (COVID-19) outbreak in Italy, especially in Lombardy and Bergamo city, represented probably nowadays one of the first major clusters of COVID-19 in the world. The aim of this report is to describe the activity of Bergamo Teratology Information Service (TIS) in supporting the public and health-care personnel in case of drug prescriptions in suspected/confirmed COVID-19 pregnant and lactating patients during COVID-19 outbreak in Italy. Methods All Bergamo TIS requests concerning COVID-19 pregnant and lactating women have been retrospectively evaluated from 1 March to 15 April 2020. Type of medications, drug's safety profile and compatibility with pregnancy and lactation are reported. Results Our service received information calls concerning 48 (9 pregnant, 35 lactating) patients. Among pregnant and lactating women, the requests of information were related to 16 and 60 drugs prescriptions respectively. More than half concerned drugs prescriptions during the first and second trimester (13/16) and during the first six months of lactation (37/60). Hydroxychloroquine and azithromycin were the most involved. Conclusions Hydroxychloroquine and azithromycin at dosages used for COVID-19 may be considered compatible and reasonably safe either in pregnancy and lactation. Antivirals may be considered acceptable in pregnancy. During lactation lopinavir and ritonavir probably exhibit some supportive data from literature that darunavir and cobicistat do not. Tocilizumab may be considered for COVID-19 treatment because no increased malformation rate were observed until now. However caution may be advised because human data are limited and the potential risk of embryo-fetal toxicity cannot be excluded.

Topics: Abnormalities, Drug-Induced; Adult; Antiviral Agents; Azithromycin; Betacoronavirus; Congenital Abnormalities; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Prescriptions; Female; Gestational Age; Humans; Hydroxychloroquine; Italy; Lactation; Maternal-Fetal Exchange; Middle Aged; Pandemics; Pneumonia, Viral; Pregnancy; Pregnancy Complications, Infectious; SARS-CoV-2; Teratology

The COVID-19 pandemic has posed major challenges to all aspects of healthcare. Malta's population density, large proportion of elderly and high prevalence of diabetes and obesity put the country at risk of uncontrolled viral transmission and high mortality. Despite this, Malta achieved low mortality rates compared to figures overseas. The aim of this paper is to identify key factors that contributed to these favorable outcomes.. This is a retrospective, observational, nationwide study which evaluates outcomes of patients during the first wave of the pandemic in Malta, from the 7th of March to the 24th of April 2020. Data was collected on demographics and mode of transmission. Hospitalization rates to Malta's main general hospital, Mater Dei Hospital, length of in-hospital stay, intensive care unit admissions and 30-day mortality were also analyzed.. There were 447 confirmed cases in total; 19.5% imported, 74.2% related to community transmission and 6.3% nosocomially transmitted. Ninety-three patients (20.8%) were hospitalized, of which 4 were children. Patients with moderate-severe disease received hydroxychloroquine and azithromycin, in line with evidence available at the time. A total of 4 deaths were recorded, resulting in an all-cause mortality of 0.89%. Importantly, all admitted patients with moderate-severe disease survived to 30-day follow up.. Effective public health interventions, widespread testing, remote surveillance of patients in the community and a low threshold for admission are likely to have contributed to these favorable outcomes. Hospital infection control measures were key in preventing significant nosocomial spread. These concepts can potentially be applied to stem future outbreaks of viral diseases. Patients with moderate-severe disease had excellent outcomes with no deaths reported at 30-day follow up.

Topics: Adult; Aged; Antiviral Agents; Azithromycin; Coronavirus Infections; COVID-19; Drug Utilization; Female; Hospitalization; Humans; Hydroxychloroquine; Intensive Care Units; Length of Stay; Male; Malta; Middle Aged; Pandemics; Pneumonia, Viral; Survival Analysis

To describe the clinical characteristics and management of severe COVID-19 patients.. Observational, descriptive, longitudinal, and retrospective study.. 56 patients were admitted, of whom 80.3% (n = 45) were males with a mean age of 58 years [46-67]. The main comorbidities were obesity, high blood pressure, and diabetes. Symptoms onset time at admittance to the ICU was 9 [7-14] days, of which the most frequent were dyspnea, fever, and dry cough. Laboratory data were lymphopenia; elevation of LDH, fibrinogen, D-dimer, ferritin and CRP. 100% of the patients required mechanical ventilation, the median mechanical ventilation time was 12 [6-17] days, and 66% (n= 37) required a prone position. The pharmacological treatment was mainly based on azithromycin, hydroxychloroquine, tocilizumab and steroids. The most frequent complications were acute kidney injury, venous thromboembolism and acute myocardial infarction. Mortality rate was 17.8% (n = 10).. The characteristics of the critically ill patients in our hospital were mostly elderly and obese, with the variables of higher SOFA score and acute kidney injury associated with higher mortality.. Describir las características clínicas y el manejo de pacientes graves con COVID-19.. Estudio observacional, descriptivo, longitudinal y restrospectivo.. Ingresaron 56 pacientes, el 80.3% (n = 45) de sexo masculino, con un promedio de edad de 58 [46-67] años. Las principales condiciones de comorbilidad fueron obesidad, hipertensión y diabetes. El tiempo de inicio de los síntomas al ingreso fue de 9 [7-14] días, siendo los más frecuentes disnea, fiebre y tos seca. Los datos de laboratorio fueron linfopenia y elevación de deshidrogenasa láctica, fibrinógeno, dímero D, ferritina y proteína C reactiva. El 100% de los pacientes requirieron ventilación mecánica, con una mediana de tiempo de ventilación de 12 [6-17] días, y el 66% (n = 37) requirieron posición en prono. El tratamiento farmacólogico fue a base de azitromicina, hidroxicloroquina, tocilizumab y esteroides, principalmente. Las complicaciones más frecuentes fueron lesión renal aguda, enfermedad tromboembólica venosa e infarto agudo al miocardio. La tasa de mortalidad fue del 17.8% (n = 10).. Los pacientes graves en nuestro hospital fueron en su mayoría personas de la tercera edad y con obesidad, siendo las variables de mayor puntaje SOFA y lesión renal aguda las asociadas con mayor mortalidad.

Topics: Acute Kidney Injury; Adrenal Cortex Hormones; Aged; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azithromycin; Betacoronavirus; Cardiovascular Diseases; Combined Modality Therapy; Comorbidity; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Critical Care; Female; Hospital Mortality; Hospitals, University; Humans; Hydroxychloroquine; Intensive Care Units; Male; Mexico; Middle Aged; Organ Dysfunction Scores; Pandemics; Pneumonia, Viral; Respiration, Artificial; SARS-CoV-2; Symptom Assessment

Topics: Anti-Infective Agents; Azithromycin; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Monitoring, Immunologic; Mycophenolic Acid; Oxygen Inhalation Therapy; Pandemics; Pneumonia, Viral; Prednisolone; SARS-CoV-2; Tacrolimus; Treatment Outcome

In December 2019 a new strain of coronavirus SARS-CoV-2 has emerged and affected health care worldwide. Patients with cancer and other comorbidities are at increased risk for adverse outcomes in this infection.. In this case report we present a 75-year-old patient with a localized gastric adenocarcinoma, currently treated by perioperative chemotherapy regimen, who had an rT-PCR proven novel coronavirus SARS-CoV-2 infection. Laboratory and radiologic assessments were performed in order to assess disease severity; however, the findings were not altered in accordance with the findings associated with COVID-19 disease.. On the first hospital day the patient had a low grade fever with chills. Subsequently a pharmacological therapy with hydroxychloroquine and azithromycin was started. After pharmacologic and symptomatic treatment, the patient was reassessed for SARS-CoV-2, with negative results. At discharge, the patient was ordered a 14-day mandatory quarantine. After 57 days of follow-up, the patient underwent a new rapid antibody test by Acro Biotech inc., which gave negative results for IgM and IgG.. An infection with SARS-CoV-2 is associated with a more severe disease in patients with comorbidities and cancer; however, this case patient had a mild course of COVID-19 disease. The aim of this case report is to share the information on the clinical course and outcomes of a patient with malignancy. Rapid spreading of information is crucial in the management of COVID-19.

Topics: Adenocarcinoma; Aged; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Male; Pandemics; Patient Discharge; Pneumonia, Viral; SARS-CoV-2; Slovakia; Stomach Neoplasms; Treatment Outcome

Individuals with large followings can influence public opinions and behaviors, especially during a pandemic. In the early days of the pandemic, US president Donald J Trump has endorsed the use of unproven therapies. Subsequently, a death attributed to the wrongful ingestion of a chloroquine-containing compound occurred.. We investigated Donald J Trump's speeches and Twitter posts, as well as Google searches and Amazon purchases, and television airtime for mentions of hydroxychloroquine, chloroquine, azithromycin, and remdesivir.. Twitter sourcing was catalogued with Factba.se, and analytics data, both past and present, were analyzed with Tweet Binder to assess average analytics data on key metrics. Donald J Trump's time spent discussing unverified treatments on the United States' 5 largest TV stations was catalogued with the Global Database of Events, Language, and Tone, and his speech transcripts were obtained from White House briefings. Google searches and shopping trends were analyzed with Google Trends. Amazon purchases were assessed using Helium 10 software.. From March 1 to April 30, 2020, Donald J Trump made 11 tweets about unproven therapies and mentioned these therapies 65 times in White House briefings, especially touting hydroxychloroquine and chloroquine. These tweets had an impression reach of 300% above Donald J Trump's average. Following these tweets, at least 2% of airtime on conservative networks for treatment modalities like azithromycin and continuous mentions of such treatments were observed on stations like Fox News. Google searches and purchases increased following his first press conference on March 19, 2020, and increased again following his tweets on March 21, 2020. The same is true for medications on Amazon, with purchases for medicine substitutes, such as hydroxychloroquine, increasing by 200%.. Individuals in positions of power can sway public purchasing, resulting in undesired effects when the individuals' claims are unverified. Public health officials must work to dissuade the use of unproven treatments for COVID-19.

Topics: Adenosine Monophosphate; Alanine; Azithromycin; Chloroquine; Communication; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Federal Government; Fraud; Humans; Hydroxychloroquine; Internet; Language; Mass Media; Pandemics; Pneumonia, Viral; Public Health; United States

Combination of hydroxychloroquine and azithromycin for the treatment of coronavirus disease 2019 (COVID-19) carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias..  To characterize the ventricular repolarization indexes which are associated with malignant ventricular arrhythmias in patients treated with hydroxychloroquine and concomitant azithromycin for COVID-19.. A total of 81 patients who had hydroxychloroquine and azithromycin combination therapy because of possible or  reverse-transcription polymertase chain reaction (RT-PCR) confirmed diagnosis of COVID-19 were included in the study. Baseline and control electrocardiograms (before and after treatment) were analyzed retrospectively. Tp-e interval, Tp-e/QT and Tp-e/QTc ratios, which are ventricular repolarization indexes, were calculated.. While there was no significant increase in QTc interval in patients receiving combination therapy, there was a significant increase in ventricular repolarization indexes.. The increase in ventricular replarization indexes is associated with the risk of arrhythmia. In patients using QTc prolonging medication for COVID-19 treatment, QTc monitoring alone may not be sufficient to follow-up for arrhythmia. Even if there is no prolongation in QTc, an increase in ventricular repolarization indexes may be seen (Tab. 5, Ref. 37).

Topics: Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Electrocardiography; Humans; Hydroxychloroquine; Long QT Syndrome; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2

The new coronavirus 2019 epidemic declared in China on December 31, 2019 soon spread to the rest of the world, becoming the subject of an unprecedented health pandemic according to the World Health Organization's declaration of March 11, 2020. It is a disease that has the potential to cause multiple systemic infections. We report here the case of an acute polyradiculoneuritis of the Guillain-Barré type (GBS) indicative of a COVID-19 infection. This is a 41 year old patient seen for ascending, symmetrical and bilateral, progressive and acute tetraparesis with in a context of influenza syndrome and digestive infections treated 2 weeks earlier. During a COVID-19 infection, certain inflammatory cells stimulated by the virus produce inflammatory cytokines creating immune-mediated processes. The same mechanism is observed in GBS being also an immune-mediated disorder. The management of this disease in COVID-19 positive patients does not differ from that of patients who do not carry the virus. The risk of respiratory distress in COVID-19 positive patients becomes twice as great in patients with GBS who test positive for COVID-19 at the same time. Monitoring for hemodynamic disorders and respiratory distress in a neuro-intensive care unit may be fruitful.

Topics: Adult; Atrial Fibrillation; Azithromycin; Betacoronavirus; Chloroquine; Clinical Laboratory Techniques; Combined Modality Therapy; Contraindications, Drug; Coronavirus Infections; COVID-19; COVID-19 Testing; Early Diagnosis; Guillain-Barre Syndrome; Humans; Male; Muscle Weakness; Nasopharynx; Olfaction Disorders; Oxygen Inhalation Therapy; Pandemics; Pneumonia, Viral; Quadriplegia; Respiration, Artificial; SARS-CoV-2; Urinary Incontinence

Rhodococcus equi is a common cause of pneumonia in animals. Human infection is rare. Increasing number of cases are being reported in immunosuppressed individuals mostly associated with HIV infection, but also in solid organ transplant recipients and leukemia/lymphoma patients. We report on an adult male who developed pneumonia and gastroenteritis 4 mo after receiving a renal transplant. CT scan of the lungs showed a dominant 2.5-cm upper lobe lung mass and smaller bilateral nodules. He underwent a diagnostic bronchoscopy with fine-needle aspiration biopsy of the largest lung nodule. Smears showed histiocytic granulomatous inflammation, foamy macrophages, and acute inflammatory exudate. Scattered foamy macrophages displayed intracellular coccobacilli identifiable on Diff-Quik stain. A few cells with changes suggestive of viral inclusions were identified. Cytomegalovirus (CMV) immunostain was positive in the cell block sections. Lung cultures grew R. equi. To the best of our knowledge, this is the first report of coinfection with R. equi and CMV.

Topics: Actinomycetales Infections; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antigens, Viral; Antiviral Agents; Azithromycin; Biopsy, Needle; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Immunocompromised Host; Kidney Transplantation; Male; Ofloxacin; Pneumonia, Bacterial; Pneumonia, Viral; Postoperative Complications; Rhodococcus; Tomography, X-Ray Computed; Vancomycin

Intravenous azithromycin is increasingly administered for treatment of hospitalized patients with community-acquired pneumonia. Macrolide antibiotics cause ototoxicity, which occurs most frequently when high serum concentrations are achieved. Current dosing guidelines for intravenous azithromycin can result in much higher serum concentrations than is seen with oral administration. We describe a 47-year-old woman who developed complete deafness after receiving 8 days of intravenous azithromycin.

Topics: Anti-Bacterial Agents; Azithromycin; Deafness; Female; Humans; Injections, Intravenous; Middle Aged; Pneumonia, Viral