zithromax and favipiravir

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

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

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

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

Due to current advances and growing experience in the management of coronavirus Disease 2019 (COVID-19), the outcome of COVID-19 patients with severe/critical illness would be expected to be better in the second wave compared with the first wave. As our hospitalization criteria changed in the second wave, we aimed to investigate whether a favorable outcome occurred in hospitalized COVID-19 patients with only severe/critical illness. Among 642 laboratory-confirmed hospitalized COVID-19 patients in the first wave and 1121 in the second wave, those who met World Health Organization (WHO) definitions for severe or critical illness on admission or during follow-up were surveyed. Data on demographics, comorbidities, C-reactive protein (CRP) levels on admission, and outcomes were obtained from an electronic hospital database. Univariate analysis was performed to compare the characteristics of patients in the first and second waves. There were 228 (35.5%) patients with severe/critical illness in the first wave and 681 (60.7%) in the second wave. Both groups were similar in terms of age, gender, and comorbidities, other than chronic kidney disease. Median serum CRP levels were significantly higher in patients in the second wave compared with those in the first wave [109 mg/L (interquartile range [IQR]: 65-157) vs. 87 mg/L (IQR: 39-140); p < 0.001]. However, intensive care unit admission and mortality rates were similar among the waves. Even though a lower mortality rate in the second wave has been reported in previous studies, including all hospitalized COVID-19 patients, we found similar demographics and outcomes among hospitalized COVID-19 patients with severe/critical illness in the first and second wave.

Topics: Aged; Amides; Antibodies, Monoclonal, Humanized; Azithromycin; C-Reactive Protein; Comorbidity; COVID-19; COVID-19 Drug Treatment; Critical Care; Drug Combinations; Enoxaparin; Female; Hospital Mortality; Hospitalization; Humans; Hydroxychloroquine; Interleukin 1 Receptor Antagonist Protein; Lopinavir; Male; Methylprednisolone; Middle Aged; Pyrazines; Retrospective Studies; Ritonavir; SARS-CoV-2; Severity of Illness Index; Treatment Outcome; Turkey

Patients with solid malignancies are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection than the healthy population. The outcome of SARS-CoV-2 infection in highly immunosuppressed populations, such as in patients with hematological malignancies, is a point of interest. We aimed to analyze the symptoms, complications, intensive care unit admissions, and mortality rates of patients with hematological malignancies infected with SARS-CoV-2 in Turkey.. In this multicenter study, we included 340 adult and pediatric patients diagnosed with SARS-CoV-2 from March to November 2020. Diagnosis and status of primary disease, treatment schedules for hematological malignancies, time from last treatment, life expectancy related to the hematological disease, and comorbidities were recorded, together with data regarding symptoms, treatment, and outcome of SARS-CoV-2 infection.. Forty four patients were asymptomatic at diagnosis of SARS-CoV- 2 infection. Among symptomatic patients, fever, cough, and dyspnea were observed in 62.6%, 48.8%, and 41.8%, respectively. Sixty-nine (20%) patients had mild SARS-CoV-2 disease, whereas moderate, severe, and critical disease was reported in 101 (29%), 71 (20%), and 55 (16%) patients, respectively. Of the entire cohort, 251 (73.8%) patients were hospitalized for SARS-CoV-2. Mortality related to SARS-CoV-2 infection was 26.5% in the entire cohort; this comprised 4.4% of those patients with mild disease, 12.4% of those with moderate disease, and 83% of those with severe or critical disease. Active hematological disease, lower life expectancy related to primary hematological disease, neutropenia at diagnosis of SARS-CoV-2, ICU admission, and first-line therapy used for coronavirus disease-2019 treatment were found to be related to higher mortality rates. Treatments with hydroxychloroquine alone or in combination with azithromycin were associated with a higher rate of mortality in comparison to favipiravir use.. Patients with hematological malignancy infected with SARS-CoV-2 have an increased risk of severe disease and mortality.. Solid malignite hastalarının şiddetli akut solunum yolu enfeksiyonu-koronavirüs-2 (SARS-CoV-2) enfeksiyonuna sağlıklı bireylerden daha yatkın oldukları gösterilmiştir. Bu verilerin ardından oldukça yoğun immünosupresif olan hematolojik malignite hastalarında SARS-CoV-2 infeksiyonu sonuçları ilgi konusu olmuştur. Biz de bu makalede Türkiye’de hematolojik malignite tanısı ile takip ve tedavi edilirken SARS-CoV-2 enfeksiyonu saptanan hastaların semptom, komplikasyon, yoğun bakım ünitesine yatış ve mortalite oranlarını değerlendirmeyi amaçladık.. Çok merkezli çalışmamıza Mart-Kasım 2020 tarihleri arasında SARS-CoV-2 enfeksiyonu tanısı alan erişkin ve pediatrik 340 hastayı dahil ettik. Hastaların hematolojik malignite tanıları, hastalık statusları, tedavileri, son tedaviden enfeksiyona kadar geçen süre, komorbiditeleri, yaşam beklentileri değerlendirildi. Semptomları, oluşan komplikasyonlar ve sonuçlar analiz edildi.. Kırk-dört hasta semptomsuz olarak enfeksiyonu geçirirken, semptomatik hastaların ateş, öksürük, ve dispne oranları sırasıyla %62,6, %48,8 ve %41,8 idi. Altmış altı hasta (%20) hastalığı hafif geçirirken, orta, ciddi ve kritik hastalık tanısı alanların oranı sırasıyla %29, %20 ve %16 idi. Tüm kohortta ölüm oranı %26,6 idi; ölüm hafif hastalığı olanlarda %4,4 , orta derece hastalık geçirenlerde %12 ve ciddi/kritik hastalık geçirenlerde ise %83 olarak saptandı. Aktif hematolojik hastalık olması, primer hematolojik hastalığa bağlı düşük hayat beklentisi, SARS-CoV-2 tanısı aldığında nötropenik olmak, yoğun bakıma alınmış olmak ve ilk sıra koronavirüs hastalığı-2019 tedavisi yüksek ölüm riski ile ilişkilendirilen faktörlerdendi. Tek başına veya azitromisin ile kombine olarak hidroksiklorokin kullanan hastaların sadece favipiravir kullananlara göre ölüm riskleri daha yüksek saptandı.. SARS-CoV-2 infeksiyonu geçiren hematolojik malignite hastalarında daha yüksek oranda ciddi hastalık ve ölüm riski gözlenmektedir.

Topics: Adult; Amides; Azithromycin; Child; COVID-19; Hematologic Neoplasms; Humans; Hydroxychloroquine; Pyrazines; SARS-CoV-2; Turkey

Despite the fact that the COVID-19 pandemic has been going on for over 5 months, there is yet to be a standard management policy for all patients including those with mild-to-moderate cases. We evaluated the role of early hospitalization in combination with early antiviral therapy with COVID-19 patients in a tertiary care university hospital.. This was a prospective, observational, single-center study on probable/confirmed COVID-19 patients hospitalized in a tertiary care hospital on COVID-19 wards between March 20 and April 30, 2020. The demographic, laboratory, and clinical data were collected.. We included 174 consecutive probable/confirmed COVID-19 adult patients hospitalized in the Internal Medicine wards of the University Adult Hospital between March 20 and April 30, 2020. The median age was 45.5 (19–92) years and 91 patients (52.3%) were male. One hundred and twenty (69%) were confirmed microbiologically, 41 (23.5%) were radiologically diagnosed, and 13 (7.5%) were clinically suspected (negative microbiological and radiological findings compatible with COVID-19); 35 (20.1%) had mild, 107 (61.5%) moderate disease, and 32 (18.4%) had severe pneumonia. Out of 171 cases, 130 (74.3%) showed pneumonia; 80 were typical, and 50 showed indeterminate infiltration for COVID-19. Patients were admitted within a median of 3 days (0-14 days) after symptoms appear. The median duration of hospitalization was 4 days (0-28 days). In this case series, 13.2% patients were treated with hydroxychloroquine alone, 64.9% with hydroxychloroquine plus azithromycin, and 18.4% with regimens including favipiravir. A total of 15 patients (8.5%) were transferred to the ICU. Four patients died (2.2%).. In our series, 174 patients were admitted to the hospital wards for COVID-19, 69% were confirmed with PCR and/or antibody test. At the time of admission, nearly one fifth of the patients had severe diseases. Of the patients, 95.4% received hydroxychloroquine alone or in combination. The overall case fatality rate was 2.2%.

Topics: Adult; Aged; Aged, 80 and over; Amides; Anti-Bacterial Agents; Antiviral Agents; Azithromycin; COVID-19 Drug Treatment; Drug Therapy, Combination; Early Medical Intervention; Early Warning Score; Female; Hospitalization; Humans; Hydroxychloroquine; Intensive Care Units; Length of Stay; Male; Middle Aged; Prospective Studies; Pyrazines; SARS-CoV-2; Severity of Illness Index; Treatment Outcome; Young Adult

The present COVID-19 pandemic has prompted worldwide repurposing of drugs. The aim of the present work was to develop and validate a two-dimensional isotope-dilution liquid chromatrography tandem mass spectrometry (ID-LC-MS/MS) method for accurate quantification of remdesivir and its active metabolite GS-441524, chloroquine, hydroxychloroquine, lopinavir, ritonavir, favipiravir and azithromycin in serum; drugs that have gained attention for repurposing in the treatment of COVID-19.. Following protein precipitation, samples were separated with a two-dimensional ultra-high performance liquid chromatography (2D-UHPLC) setup, consisting of an online solid phase extraction (SPE) coupled to an analytical column. For quantification, stable isotope-labelled analogues were used as internal standards for all analytes. The method was validated on the basis of the European Medicines Agency bioanalytical method validation protocol.. Detuning of lopinavir and ritonavir allowed simultaneous quantification of all analytes with different concentration ranges and sensitivity with a uniform injection volume of 5 μL. The method provided robust validation results with inaccuracy and imprecision values of ≤ 9.59 % and ≤ 11.1 % for all quality controls.. The presented method is suitable for accurate and simultaneous quantification of remdesivir, its metabolite GS-441525, chloroquine, hydroxychloroquine, lopinavir, ritonavir, favipiravir and azithromycin in human serum. The quantitative assay may be an efficient tool for the therapeutic drug monitoring of these potential drug candidates in COVID-19 patients in order to increase treatment efficacy and safety.

Topics: Adenosine; Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Azithromycin; Chloroquine; Chromatography, Liquid; COVID-19; COVID-19 Drug Treatment; Furans; Humans; Hydroxychloroquine; Isotopes; Lopinavir; Pandemics; Pyrazines; Pyrroles; Ritonavir; SARS-CoV-2; Tandem Mass Spectrometry; Triazines

Topics: Amides; Antiviral Agents; Azithromycin; Child; COVID-19; COVID-19 Serotherapy; Ectodermal Dysplasia; Genetic Diseases, X-Linked; Humans; Hydroxychloroquine; I-kappa B Kinase; Immunization, Passive; Male; Primary Immunodeficiency Diseases; Pyrazines; SARS-CoV-2

To screen several antiviral drugs systematically for their efficacy against type B coxsackieviruses.. Ten drugs with different antiviral mechanisms were analysed for their efficacy against prototype strains of type B coxsackieviruses in A549 cells. Cell viability was quantified in fixed cells using a colorimetric assay. Median effective dose was interpolated from the triplicated experiments and the dose-response curves were generated for each drug-virus combination. Drug cytotoxicity was similarly quantified and selectivity indices calculated.. Hizentra, pleconaril, fluoxetine, norfluoxetine, ribavirin, favipiravir, and guanidine hydrochloride were able to abrogate infection by all tested viruses, with the exception of complete inefficacy of pleconaril against coxsackievirus B3 and favipiravir against coxsackievirus B2. The effective doses for Hizentra, enviroxime, ribavirin, favipiravir, and pleconaril were clearly below their therapeutic serum concentrations, while the effective concentrations of fluoxetin, norfluoxetine and itraconazole exceeded their therapeutic serum concentrations. Lovastatin and azithromycin did not efficiently block type B coxsackieviruses.. Hizentra, enviroxime, pleconaril, ribavirin, and favipiravir are effective against type B coxsackieviruses in vitro in their therapeutic serum concentrations. These antiviral drugs are therefore attractive candidates for type 1 diabetes prevention/treatment trials. They can also be used in other clinical conditions caused by type B coxsackieviruses.

Topics: A549 Cells; Amides; Antiviral Agents; Azithromycin; Benzimidazoles; Coxsackievirus Infections; Diabetes Mellitus, Type 1; Drug Repositioning; Enterovirus B, Human; Fluoxetine; Guanidine; Humans; Immunoglobulin G; Lovastatin; Oxadiazoles; Oxazoles; Oximes; Pyrazines; Ribavirin; Sulfonamides

The SARS-CoV-2 has wreaked havoc globally and has claimed innumerable lives all over the world. The symptoms of this disease may range from mild influenza-like symptoms to severe acute respiratory distress syndrome with high morbidity and mortality. With improved diagnostic techniques and better disease understanding, an increased number of cases are being reported with extrapulmonary manifestations of this disease ranging from renal and gastrointestinal to cardiac, hepatic, neurological and haematological dysfunction. Subacute thyroiditis is a self-limiting and painful thyroid gland inflammation most often secondary to viral infections. We report a case of subacute thyroiditis in a 58-year-old gentleman presenting with a painful swelling in the neck who was subsequently detected to be positive for SARS-CoV-2. We seek to highlight the broad clinical spectrum of the COVID-19 by reporting probably the first case of subacute thyroiditis possibly induced by SARS-CoV-2 infection from India.

Topics: Amides; Antiviral Agents; Azithromycin; COVID-19; COVID-19 Drug Treatment; Diagnosis, Differential; Glucocorticoids; Humans; Male; Middle Aged; Prednisolone; Pyrazines; Radionuclide Imaging; SARS-CoV-2; Thyroid Function Tests; Thyroid Gland; Thyroiditis, Subacute; Treatment Outcome; Ultrasonography, Doppler, Color