zithromax and Cytokine-Release-Syndrome

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

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

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

Azithromycin, an antibiotic with potential antiviral and anti-inflammatory properties, has been used to treat COVID-19, but evidence from community randomised trials is lacking. We aimed to assess the effectiveness of azithromycin to treat suspected COVID-19 among people in the community who had an increased risk of complications.. In this UK-based, primary care, open-label, multi-arm, adaptive platform randomised trial of interventions against COVID-19 in people at increased risk of an adverse clinical course (PRINCIPLE), we randomly assigned people aged 65 years and older, or 50 years and older with at least one comorbidity, who had been unwell for 14 days or less with suspected COVID-19, to usual care plus azithromycin 500 mg daily for three days, usual care plus other interventions, or usual care alone. The trial had two coprimary endpoints measured within 28 days from randomisation: time to first self-reported recovery, analysed using a Bayesian piecewise exponential, and hospital admission or death related to COVID-19, analysed using a Bayesian logistic regression model. Eligible participants with outcome data were included in the primary analysis, and those who received the allocated treatment were included in the safety analysis. The trial is registered with ISRCTN, ISRCTN86534580.. The first participant was recruited to PRINCIPLE on April 2, 2020. The azithromycin group enrolled participants between May 22 and Nov 30, 2020, by which time 2265 participants had been randomly assigned, 540 to azithromycin plus usual care, 875 to usual care alone, and 850 to other interventions. 2120 (94%) of 2265 participants provided follow-up data and were included in the Bayesian primary analysis, 500 participants in the azithromycin plus usual care group, 823 in the usual care alone group, and 797 in other intervention groups. 402 (80%) of 500 participants in the azithromycin plus usual care group and 631 (77%) of 823 participants in the usual care alone group reported feeling recovered within 28 days. We found little evidence of a meaningful benefit in the azithromycin plus usual care group in time to first reported recovery versus usual care alone (hazard ratio 1·08, 95% Bayesian credibility interval [BCI] 0·95 to 1·23), equating to an estimated benefit in median time to first recovery of 0·94 days (95% BCI -0·56 to 2·43). The probability that there was a clinically meaningful benefit of at least 1·5 days in time to recovery was 0·23. 16 (3%) of 500 participants in the azithromycin plus usual care group and 28 (3%) of 823 participants in the usual care alone group were hospitalised (absolute benefit in percentage 0·3%, 95% BCI -1·7 to 2·2). There were no deaths in either study group. Safety outcomes were similar in both groups. Two (1%) of 455 participants in the azothromycin plus usual care group and four (1%) of 668 participants in the usual care alone group reported admission to hospital during the trial, not related to COVID-19.. Our findings do not justify the routine use of azithromycin for reducing time to recovery or risk of hospitalisation for people with suspected COVID-19 in the community. These findings have important antibiotic stewardship implications during this pandemic, as inappropriate use of antibiotics leads to increased antimicrobial resistance, and there is evidence that azithromycin use increased during the pandemic in the UK.. UK Research and Innovation and UK Department of Health and Social Care.

Topics: Age Factors; Aged; Aged, 80 and over; Antimicrobial Stewardship; Azithromycin; COVID-19; COVID-19 Drug Treatment; Cytokine Release Syndrome; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Patient Admission; Risk Factors; SARS-CoV-2; Time Factors; Treatment Outcome; United Kingdom

Mediators of immunity and inflammation are playing a crucial role in COVID-19 pathogenesis and complications as demonstrated by several genetic and clinical studies. Thus, repurposing of drugs that possess anti-inflammatory and/or immune-modulatory effects for COVID-19 is considered a rational approach.. We analyze selected studies that correlated COVID-19 with dysregulated interferon and inflammatory responses while reflecting on our academic and real-life experience using non-steroidal anti-inflammatory drugs, nitazoxanide and azithromycin for management of COVID-19. Moreover, we interpret the results that suggested a potential survival benefit of low-dose aspirin and colchicine when used for COVID-19.. Nitazoxanide/azithromycin combination has been first hypothesized by the author and practiced by him and several researchers to benefit COVID-19 patients due to a potential ability to augment the natural interferon response as well as their positive immunomodulatory effects on several cytokines. Furthermore, NSAIDs, that are unfortunately currently at best of second choice after paracetamol, have been early postulated and clinically practiced by the author to prevent or ameliorate COVID-19 complications and mortality due to their anti-inflammatory and immunomodulatory properties. Finally, we repeat our previous call to adopt our observational study that used these drugs in sufficiently powered double blind randomized clinical trials.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Azithromycin; COVID-19; COVID-19 Drug Treatment; Cytokine Release Syndrome; Drug Repositioning; Humans; Interferons; Interleukin-6; Nitro Compounds; Observational Studies as Topic; SARS-CoV-2; Thiazoles

Blocking IL-6 pathways with sarilumab, a fully human anti-IL-6R antagonist may potentially curb the inflammatory storm of SARS-CoV2. In the present emergency scenario, we used "off-label" sarilumab in 5 elderly patients in life-threatening condition not candidates to further active measures. We suggest that sarilumab can modulate severe COVID-19-associated Cytokine Release Syndrome.

Topics: Aged; Anti-Infective Agents; Antibodies, Monoclonal, Humanized; Azithromycin; Comorbidity; COVID-19; COVID-19 Drug Treatment; Critical Illness; Cytokine Release Syndrome; Humans; Hydroxychloroquine; Interleukin-6; Male; Middle Aged; Respiration, Artificial; Retrospective Studies; RNA, Viral; SARS-CoV-2

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

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