is remdesivir an effective treatment for COVID-19

Compassionate Use of Remdesivir in Covid-19.

Remdesivir as a possible therapeutic option for the COVID-19

Compassionate Use of Remdesivir in Covid-19

Uncertainty about the Efficacy of Remdesivir on COVID-19

Remdesivir in covid-19

Remdesivir in covid-19.

Remdesivir Receives Emergency Use Authorization for Severely Ill Patients with COVID-19.

Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies

BACKGROUND & AIMS: Remdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19. METHODS: We systematically searched the PubMed, ClinicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as "Remdesivir" or 'GS-5734â³ AND "COVID-19" or "SARS-CoV-2" and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19. RESULTS: Initial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality. CONCLUSIONS: Remdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials.

Remdesivir Receives Emergency Use Authorization for Severely Ill Patients with COVID-19

Small Study Finds Remdesivir Benefit in COVID-19 But Questions Remain

Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit

Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5-9 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. Graphical abstract.

BACKGROUND & AIMS: Remdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19. METHODS: We systematically searched the PubMed, ClinicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as “Remdesivir” or ‘GS-5734″ AND “COVID-19” or “SARS-CoV-2” and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19. RESULTS: Initial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality. CONCLUSIONS: Remdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials.

Synergistic effect of Vitamin D and Remdesivir can fight COVID-19.

Treatment options for COVID-19: The reality and challenges

Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5–9 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. [Figure: see text]

Treatment options for COVID-19: the reality and challenges

Abstract 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.

Synergistic effect of vitamin D and remdesivir can fight COVID-19

COVID-19 remedies

Repurposing Therapeutics for Potential Treatment of SARS-CoV-2: A Review.

The need for proven disease-specific treatments for the novel pandemic coronavirus SARS-CoV-2 necessitates a worldwide search for therapeutic options. Since the SARS-CoV-2 virus shares extensive homology with SARS-CoV and MERS-CoV, effective therapies for SARS-CoV and MERS-CoV may also have therapeutic potential for the current COVID-19 outbreak. To identify therapeutics that might be repositioned for treatment of the SARS-CoV-2 disease COVID-19, we strategically reviewed the literature to identify existing therapeutics with evidence of efficacy for the treatment of the three coronaviruses that cause severe respiratory illness (SARS-CoV, MERS-CoV, and SARS-CoV-2). Mechanistic and in vitro analyses suggest multiple promising therapeutic options with potential for repurposing to treat patients with COVID-19. Therapeutics with particularly high potential efficacy for repurposing include camostat mesylate, remdesivir, favipiravir, tocilizumab, baricitinib, convalescent plasma, and humanized monoclonal antibodies. Camostat mesylate has shown therapeutic potential, likely by preventing viral entry into epithelial cells. In early research, the targeted antivirals remdesivir and favipiravir appear to benefit patients by decreasing viral replication; clinical trials suggest that remdesivir speeds recovery from COVID-19. Tocilizumab and baricitinib appear to improve mortality by preventing a severe cytokine storm. Convalescent plasma and humanized monoclonal antibodies offer passive immunity and decreased recovery time. This review highlights potential therapeutic options that may be repurposed to treat COVID-19 and suggests opportunities for further research.

Repurposing Therapeutics for Potential Treatment of SARS-CoV-2: A Review

Remdesivir for the Treatment of Covid-19 - Preliminary Report.

Available Evidence and Ongoing Clinical Trials of Remdesivir: Could It Be a Promising Therapeutic Option for COVID-19?

The novel coronavirus strain, severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19 emerged in Wuhan, China, in December 2019 and is skyrocketing throughout the globe and become a global public health emergency. Despite promising preventive measures being taken, there is no vaccine or drug therapy officially approved to prevent or treat the infection. Everybody is waiting the findings of ongoing clinical trials in various chemical and biological products. This review is specifically aimed to summarize the available evidence and ongoing clinical trials of remdesivir as a potential therapeutic option for COVID-19. Remdesivir is an investigational drug having broad spectrum antiviral activity with its target RNA dependent RNA polymerase. It has not yet been officially approved for Ebola and Coronaviruses. Several studies showed that remdesivir had promising in vitro and in vivo antiviral activities against SARS-CoV-1 and MERS-CoV strains. On the top of this, it exhibited a promising in vitro activity against SARS-CoV-2 strains though there are no published studies that substantiate its activity in vivo until the time of this review. There are few phase 3 randomized double-blind placebo controlled trials on the way to investigate the safety and efficacy of remdesivir. Of which, one completed double blind, placebo controlled trial showed that remdesivir showed faster time to clinical improvement in severe COVID-19 patients compared to placebo though not found statistically significant. In addition, two phase 3 randomized open label clinical trials coordinated by Gilead Sciences are being conducted. In addition, WHO Solidarity trial and INSERM DisCoVeRy trials (randomized open labels) were launched recently.

COVID-19 remedies.

The positive effects of covid-19.

Covid-19: Remdesivir is recommended for authorisation by European Medicines Agency

Compassionate Use of Remdesivir in Covid-19. Reply

Covid-19: Remdesivir is recommended for authorisation by European Medicines Agency.

Coping with Covid-19.

Use of Remdesivir in the Management of COVID-19: A Systematic Review on Current Evidences.

The rapid progression of corona virus disease in 2019 (COVID-19) pandemic has become an unprecedented global concern. This systemic review aimed at evaluating the available evidence on efficacy, safety to identify any promising role for compassionate use of remdesivir in patient suffered for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as re-purposeful use. We searched PubMed, EMBASE, Cochrane Library for randomized controlled trials (RCTs), prospective case series studies and case reports that evaluated use of remdesivir in COVID-19. The outcomes were mortality, recovery rate, length of hospital stay and clinical outcome. Though the drug remdesivir (RDV) is not approved by the FDA, still the "Emergency Use Authorization" (EUA) for compassionate use in severe cases is endorsed. After vigorous searching, screening and sorting of completed and published scientific evidences in electronic database, there were only 2 randomized control trial (RCT), 2 uncontrolled trials found until April 2020. We also included 3 published case reports to analyze the validity use of RDV because of the scarcity of evidence based reports. Remdesivir was thought to be one of the promising options for treating the patients of COVID-19 based on few laboratory experiments and reports from some compassionate use and case reports. The safety and efficacy of this drug in COVID-19 cases require high-quality evidence from well-designed and adequately-powered clinical trials with proper sample size for precise decision.

Remdesivir for the Treatment of Covid-19 - Preliminary Report

Covid-19: Remdesivir is helpful but not a wonder drug, say researchers.

Covid-19: Selected NHS patients will be treated with remdesivir

Efficacy of remdesivir versus placebo for the treatment of COVID-19: A protocol for systematic review and meta-analysis of randomized controlled trials

Background: In spite of the global containment on prevention efforts, the spread of coronavirus disease 2019 (COVID-19) is continuing to rise, with 1.1 million confirmed cases and 60,124 deaths recorded worldwide since 04 April 2020. The outbreak has a significant threat to international health and economy. At present, there is no approved vaccine or treatment for the disease, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. Here, we aim to conduct a systematic review and meta-analysis of randomized controlled trials to compare the effectiveness of remdesivir and placebo in patients with COVID-19. Method and analysis: We will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Google scholar databases without restriction in year of publication. We will include randomized controlled trials that assessed the effectiveness of remdesivir versus placebo for patients confirmed with COVID-19. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA 2015) guidelines for the design and reporting of the results. The primary endpoint will be time to clinical recovery. The secondary endpoints will be all cause mortality, discharged date, frequency of respiratory progression, and treatment-emergent adverse events. Two independent authors will perform study selection, data extraction, and methodology quality assessment. RevMan 5.3 software will be used for statistical analysis. Random/fixed effect model will be carried out to calculate mean differences for continuous outcomes and risk ratio for dichotomous outcomes between remdesivir and placebo. Ethics and dissemination: This study does not require ethical approval, because no participants data will be involved in this systematic review and meta-analysis. The findings of this study will be published in reputable and peer-reviewed journal. Registration: This review protocol is submitted in PROSPERO database for registration and we will include the registration number in the revised version of the manuscript. Keywords: 2019 novel coronavirus, 2019-nCoV, Coronavirus diseases 2019, COVID-19, SARS-cov-2, Remdesivir, Randomized Controlled Trials. Systematic review, Meta-analysis, protocol

Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2.

Effective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia.

Covid-19: Remdesivir is helpful but not a wonder drug, say researchers

Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2

The journey of remdesivir: from Ebola to COVID-19

Countries around the world are currently fighting the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus, belonging to the same genus as severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV. Currently, there are no proven antiviral therapies for COVID-19. Numerous clinical trials have been initiated to identify an effective treatment. One leading candidate is remdesivir (GS-5734), a broad-spectrum antiviral that was initially developed for the treatment of Ebola virus (EBOV). Although remdesivir performed well in preclinical studies, it did not meet efficacy endpoints in a randomized trial conducted during an Ebola outbreak. Remdesivir holds promise for treating COVID-19 based on in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. Overall, current data are insufficient to judge the efficacy of remdesivir for COVID-19, and the results of additional randomized studies are eagerly anticipated. In this narrative review, we provide an overview of Ebola and coronavirus outbreaks. We then summarize preclinical and clinical studies of remdesivir for Ebola and COVID-19.

Repurposing Drugs for the Management of Patients with Confirmed Coronavirus Disease 2019 (COVID-19).

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19) by the World Health Organization, is a newly emerging zoonotic agent that emerged in China in December 2019. No specific treatment for COVID-19 is currently available. Usual palliative treatment includes maintaining hydration and nutrition and controlling fever and cough. The clinical severity and extent of transmission need to be determined, and therapeutic options need to be developed and optimized. METHODS The present review discusses the recent repurposing of drugs for COVID-19 treatment. RESULTS Several compounds, including remdesivir, lopinavir, ritonavir, interferon-β, ribavirin, chloroquine/hydroxychloroquine, azithromycin, tocilizumab, and ivermectin, have emerged as promising alternatives. They block the virus from entering host cells, prevent viral replication, and attenuate exacerbation of the host's immune response. CONCLUSION Although some evidence indicates the positive actions of different classes of compounds for the treatment of COVID-19, few clinical assays have been established to definitively demonstrate their therapeutic value in humans. Multicenter clinical studies are urgently needed to validate and standardize therapeutic regimens that involve these agents. Although science has not yet presented us with a specific drug against COVID-19, the repurposing of drugs appears to be promising in our fight against this devastating disease.

Coping with Covid-19

Benefit-risk assessment for remdesivir in COVID-19

Medical Management of COVID-19: Evidence and Experience

Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and this infectious disease is termed COVID-19 in short. On a global scale, as of June 1, 2020, the World Health Organization (WHO) published statistics of 6,057,853 infected patients and 371,166 deaths worldwide. Despite reported observational data about the experimental use of certain drugs, there is no conclusively proven curative therapy for COVID-19 as of now; however, remdesivir received emergency use authorization (EUA) by the Food and Drug Administration (FDA) recently for use in patients hospitalized with COVID-19. There are several ongoing clinical trials related to the pharmacological choices of therapy for COVID-19 patients; however, drug trials related to observational studies so far have yielded mixed results and therefore have created a sense of confusion among healthcare professionals (HCPs). In this review article, we seek to collate and provide a summary of treatment strategies for COVID-19 patients with a variable degree of illness and discuss pharmacologic and other therapies intended to be used either as experimental medicine/therapy or as part of supportive care in complicated cases of COVID-19.

Compassionate Use of Remdesivir for Patients with Severe Covid-19

BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).

The positive effects of covid-19

Remdesivir in Treatment of COVID-19: A Systematic Benefit-Risk Assessment

INTRODUCTION: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit-risk assessment was designed and conducted to examine the benefit-risk profile of remdesivir in COVID-19 patients compared with standard of care, placebo or other treatments. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation, which starts with inevitably limited information (to meet the urgent unmet public health need worldwide), then update the benefit-risk evaluation as more data become available. METHODS: The Benefit-Risk Action Team (BRAT) framework was used to assess the overall benefit-risk of the use of remdesivir as a treatment for COVID-19 compared with standard of care, placebo or other treatments. We searched PubMed, Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. RESULTS: Using the BRAT method, several key benefits and risks for use of remdesivir in COVID-19 compared with placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR 1.23, 95% CI 0.87-1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) compared with the placebo group (26%); however, more patients in the remdesivir group discontinued treatment as a result of an adverse event compared with those patients receiving placebo (12% vs 5%). CONCLUSIONS: Preliminary clinical trial results suggest that there may be a favourable benefit-risk profile for remdesivir compared with placebo in severe COVID-19 infection and further data on benefits would strengthen this evaluation. There is limited safety data for remdesivir, which should be obtained in further studies. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit-risk assessment.

Case reports study of the first five patients COVID-19 treated with remdesivir in France

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as responsible for the COVID-19 outbreak worldwide. Data on treatment are scare and parallels are made between SARS-CoV-2 and other coronavirus. Remdesivir is a broad spectrum antiviral with efficient in vitro activity against SARS-CoV-2 and controversial evidence of clinical improvement in severe COVID-19 patients. We aimed to describe the clinical outcome and virological monitoring of the first five COVID-19 patients admitted in ICU for severe pneumonia related to SARS-CoV-2 and treated with remdesivir in the University hospital of Bichat, Paris, France. SARS-CoV-2 RT-qPCR in blood plasma, lower and upper respiratory tract were monitored. Among the five treated patients, two needed mechanical ventilation and one high flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load from upper respiratory tract was observed in most cases but two died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted for side effects among four patients, including 2 ALT elevations (3 to 5 N) and 2 renal failures requiring renal replacement. This case series of five COVID-19 patients requiring ICU for a respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.

Severe Covid-19.

Potential pharmacological agents for COVID-19.

A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan, China, has become a global pandemic. Currently, the management of COVID-19 infection is mainly supportive. Several clinical trials worldwide are evaluating several drugs approved for other indications, as well as multiple investigational agents for the treatment and prevention of COVID-19. Here, we give a brief overview of pharmacological agents and other therapies which are under investigation as treatment options or adjunctive agents for patients infected with COVID-19 and for chemoprophylaxis for the prevention of COVID-19 infection. At the time of writing this commentary, there is no peer-reviewed published evidence from randomized clinical trials of any pharmacological agents improving outcomes in COVID-19 patients. However, it was reported that remdesivir an investigational antiviral agent hastens clinical recovery, but a study is yet to be published in peer-reviewed medical journal.

Existing Drugs Might Treat COVID-19.

Compassionate use remdesivir for treatment of severe COVID-19 in pregnant women at a United States academic center

Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof)

Abstract The novel severe acute respiratory syndrome coronavirus 2 is causing a worldwide pandemic that may lead to a highly morbid and potentially fatal coronavirus disease-19 (COVID-19). There is currently no drug that has been proven as an effective therapy for COVID-19. Several candidate drugs are being considered and evaluated for treatment. This includes clinically-available drugs, such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir, which are being repurposed for the treatment of COVID-19. Novel experimental therapies, such as remdesivir and favipiravir, are also actively being investigated for antiviral efficacy. Clinically-available and investigational immunomodulators, such as the IL-6 inhibitors tocilizumab and sarilumab and the anti-GMCSF lenzilumab, are being tested for their anticipated effect in counteracting the pro-inflammatory cytokine environment that characterizes severe and critical COVID-19. This review article examines the evidence behind the potential use of these leading drug candidates for the treatment of COVID-19. The authors conclude, based on this review, that there is still no high-quality evidence to support any of these proposed drug therapies. The authors, therefore, encourage the enrollment of eligible patients to multiple ongoing clinical trials that assess the efficacy and safety of these candidate therapies. Until the results of controlled trials are available, none of the suggested therapeutics is clinically proven as an effective therapy for COVID-19.

Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

BACKGROUND Remdesivir, an inhibitor of viral RNA-dependent RNA polymerases, has been identified as a candidate for COVID-19 treatment. However, the therapeutic effect of remdesivir is controversial. METHODS We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from inception to June 11, 2020 for randomized controlled trials on the clinical efficacy of remdesivir. The main outcomes were discharge rate, mortality, and adverse events. This study is registered at INPLASY (INPLASY202060046). RESULTS Data of 1075 subjects showed that remdesivir significantly increased the discharge rate of patients with COVID-19 compared with the placebo (50.4% vs. 45.29%; relative risk [RR] 1.19 [95% confidence interval [CI], 1.05-1.34], I2 = 0.0%, P = 0.754). It also significantly decreased mortality (8.18% vs. 12.70%; RR 0.64 [95% CI, 0.44-0.92], I2 = 45.7%, P = 0.175) compared to the placebo. Data of 1296 subjects showed that remdesivir significantly decreased the occurrence of serious adverse events (RR 0.77 [95% CI, 0.63-0.94], I2 = 0.0%, P = 0.716). CONCLUSION Remdesivir is efficacious and safe for the treatment of COVID-19. TRIAL REGISTRATION NUMBER This study is registered at the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202060046).

Potential pharmacological agents for COVID-19

Research towards treating COVID-19.

Remdesivir in Treatment of COVID-19: A Systematic Benefit–Risk Assessment

INTRODUCTION: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit–risk assessment was designed and conducted to examine the benefit–risk profile of remdesivir in COVID-19 patients compared with standard of care, placebo or other treatments. A key objective of this study was to provide a platform for a dynamic systematic benefit–risk evaluation, which starts with inevitably limited information (to meet the urgent unmet public health need worldwide), then update the benefit–risk evaluation as more data become available. METHODS: The Benefit–Risk Action Team (BRAT) framework was used to assess the overall benefit–risk of the use of remdesivir as a treatment for COVID-19 compared with standard of care, placebo or other treatments. We searched PubMed, Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. RESULTS: Using the BRAT method, several key benefits and risks for use of remdesivir in COVID-19 compared with placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR 1.23, 95% CI 0.87–1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) compared with the placebo group (26%); however, more patients in the remdesivir group discontinued treatment as a result of an adverse event compared with those patients receiving placebo (12% vs 5%). CONCLUSIONS: Preliminary clinical trial results suggest that there may be a favourable benefit–risk profile for remdesivir compared with placebo in severe COVID-19 infection and further data on benefits would strengthen this evaluation. There is limited safety data for remdesivir, which should be obtained in further studies. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit–risk assessment.

COVID-19: Main therapeutic options

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19) by the World Health Organization, is a newly emerging zoonotic agent that emerged in China in December 2019. No specific treatment for COVID-19 is currently available. Usual palliative treatment includes maintaining hydration and nutrition and controlling fever and cough. The clinical severity and extent of transmission need to be determined, and therapeutic options need to be developed and optimized. METHODS: The present review discusses the recent repurposing of drugs for COVID-19 treatment. RESULTS: Several compounds, including remdesivir, lopinavir, ritonavir, interferon-ß, ribavirin, chloroquine/hydroxychloroquine, azithromycin, tocilizumab, and ivermectin, have emerged as promising alternatives. They block the virus from entering host cells, prevent viral replication, and attenuate exacerbation of the host's immune response. CONCLUSION: Although some evidence indicates the positive actions of different classes of compounds for the treatment of COVID-19, few clinical assays have been established to definitively demonstrate their therapeutic value in humans. Multicenter clinical studies are urgently needed to validate and standardize therapeutic regimens that involve these agents. Although science has not yet presented us with a specific drug against COVID-19, the repurposing of drugs appears to be promising in our fight against this devastating disease.

Remdesivir in Patients with Acute or Chronic Kidney Disease and COVID-19

Severe Covid-19

Research towards treating COVID-19

Pharmacotherapy Considerations in CKD Patients With COVID-19, A Narrative Review.

Treatment of coronavirus disease 2019 (COVID-19) among patients with CKD requires special pharmacotherapy considerations that are reviewed here. Literature review was done for several pharmacotherapy aspects in CKD patients including selection and modification of COVID-19 treatment, drug interactions, nephrotoxicity of drugs that are used for treatment of COVID-19 and potential risks/benefits of routine medications of CKD patients during COVID-19 pandemic. CKD patients should be treated according to local or national COVID-19 protocols as other patients. But, there is no data on using remdesivir in patients with severe CKD. Oseltamivir and ribavirin require dose modification in patients with moderate to severe CKD. Nephrolithiasis, CKD, and acute interstitial nephritis have been reported with protease inhibitors. Acute kidney injury has been reported with remdesivir in patients with severe COVID-19. Pharmacokinetic-enhanced protease inhibitors increase the concentration of some drugs such as statins, cinacalcet, steroids, calcineurin inhibitors (CNIs). Some hypothetical benefits and harms have been suggested for statins and renin-angiotensinaldosterone system inhibitors in COVID-19 patients. Continuing guideline-directed administration of these drugs is recommended. Among different immunomodulating/immunosuppressive drugs, hydroxychloroquine and CNIs are the safest ones during COVID-19. Antimetabolites are suggested to be withheld during moderate to severe COVID-19. Fluid therapy and anticoagulant prophylaxis/ treatment need special attention in CKD patients with COVID-19. CKD patients with COVID-19 are treated as other patients, with some dose modifications if needed. Be mindful for management of drug interactions as well as modification of immunosuppressive drugs in patients with moderate to severe COVID-19.

Possible therapeutic agents for COVID-19: a comprehensive review.

INTRODUCTION Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged in China. There are no available vaccines or antiviral drugs for COVID-19 patients. Herein, we represented possible therapeutic agents that may stand as a potential therapy against COVID-19. AREAS COVERED We searched PubMed, Google Scholar, and clinicaltrials.gov for relevant papers. We showed some agents with potentially favorable efficacy, acceptable safety as well as good pharmacokinetic profiles. Several therapies are under assessment to evaluate their efficacy and safety for COVID-19. However, some drugs were withdrawn due to their side effects after demonstrating some clinical efficacy. Indeed, the most effective therapies could be organ function support, convalescent plasma, anticoagulants, and immune as well as antiviral therapies, especially anti-influenza drugs due to the similarities between respiratory viruses regarding viral entry, uncoating, and replication. We encourage giving more attention to favipiravir, remdesivir, and measles vaccine. EXPERT OPINION A combination, at least dual or even triple therapy, of the aforementioned efficacious and safe therapies is greatly recommended for COVID-19. Further, patients should have a routine assessment for their coagulation and bleeding profiles as well as their inflammatory and cytokine concentrations.

Remdesivir for the Treatment of Covid-19 - Preliminary Report

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). CONCLUSIONS: Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACCT-1 ClinicalTrials.gov number, NCT04280705.).

Assessing the severity of COVID-19.

Understanding and reducing the fear of COVID-19

Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More

Abstract COVID-19 is now pandemic throughout the world. Scientist, doctors are searching for effective therapy of this diseases. The remdesivir, an antiviral drug, is appeared as ‘molecule of hope’ for the treatment of this disease. USFDA approve this drug for the treatment of COVID-19. The molecular mechanism is unknown. In this paper, we tried to describe the probable molecular mechanism of remdesivir to inhibit the RNA synthesis of SARS-CoV-2. However, more detail mechanism is needed to understand mechanism of action of remdesivir.

Existing Drugs Might Treat COVID-19

Remdesivir for the Treatment of Covid-19 — Preliminary Report

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). CONCLUSIONS: Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)

Remdesivir bei Patienten mit schwerer COVID-19./ [Remdesivir for patients with severe COVID-19]

Remdesivir in Patients with Acute or Chronic Kidney Disease and COVID-19.

How to Quantify and Interpret Treatment Effects in Comparative Clinical Studies of COVID-19

Clinical trials of treatments for coronavirus disease 2019 (COVID-19) draw intense public attention. More than ever, valid, transparent, and intuitive summaries of the treatment effects, including efficacy and harm, are needed. In recently published and ongoing randomized comparative trials evaluating treatments for COVID-19, time to a positive outcome, such as recovery or improvement, has repeatedly been used as either the primary or key secondary end point. Because patients may die before recovery or improvement, data analysis of this end point faces a competing risk problem. Commonly used survival analysis techniques, such as the Kaplan-Meier method, often are not appropriate for such situations. Moreover, almost all trials have quantified treatment effects by using the hazard ratio, which is difficult to interpret for a positive event, especially in the presence of competing risks. Using 2 recent trials evaluating treatments (remdesivir and convalescent plasma) for COVID-19 as examples, a valid, well-established yet underused procedure is presented for estimating the cumulative recovery or improvement rate curve across the study period. Furthermore, an intuitive and clinically interpretable summary of treatment efficacy based on this curve is also proposed. Clinical investigators are encouraged to consider applying these methods for quantifying treatment effects in future studies of COVID-19.

Clinical trials of treatments for coronavirus disease 2019 (COVID-19) draw intense public attention. More than ever, valid, transparent, and intuitive summaries of the treatment effects, including efficacy and harm, are needed. In recently published and ongoing randomized comparative trials evaluating treatments for COVID-19, time to a positive outcome, such as recovery or improvement, has repeatedly been used as either the primary or key secondary end point. Because patients may die before recovery or improvement, data analysis of this end point faces a competing risk problem. Commonly used survival analysis techniques, such as the Kaplan–Meier method, often are not appropriate for such situations. Moreover, almost all trials have quantified treatment effects by using the hazard ratio, which is difficult to interpret for a positive event, especially in the presence of competing risks. Using 2 recent trials evaluating treatments (remdesivir and convalescent plasma) for COVID-19 as examples, a valid, well-established yet underused procedure is presented for estimating the cumulative recovery or improvement rate curve across the study period. Furthermore, an intuitive and clinically interpretable summary of treatment efficacy based on this curve is also proposed. Clinical investigators are encouraged to consider applying these methods for quantifying treatment effects in future studies of COVID-19.

Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30(th) January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6(th) February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.

The impact of COVID-19

Current pharmacological treatments for COVID-19: What's next?

Since December 2019 SARS-Cov-2 was found responsible for the disease COVID-19, which has spread worldwide. No specific therapies/vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and a number of drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir and tocilizumab. This paper describes the main pharmacological properties of such drugs administered to patients with COVID-19, focusing on their antiviral, immune-modulatory and/or anti-inflammatory actions. Where available, data from clinical trials involving patients with COVID-19 are reported. Preliminary clinical trials seem to support their benefit. However, such drugs in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds. Nevertheless, while waiting for effective preventive measures i.e. vaccines, many clinical trials on drugs belonging to different therapeutic classes are currently underway. Their results will help us in defining the best way to treat COVID-19 and reducing its symptoms and complications.

A global treatments for coronaviruses including COVID-19

In late December 2019 in Wuhan, China, several patients with viral pneumonia were identified as 2019 novel coronavirus (2019-nCoV). So far, there are no specific treatments for patients with coronavirus disease-19 (COVID-19), and the treatments available today are based on previous experience with similar viruses such as severe acute respiratory syndrome-related coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Influenza virus. In this article, we have tried to reach a therapeutic window of drugs available to patients with COVID-19. Cathepsin L is required for entry of the 2019-nCoV virus into the cell as target teicoplanin inhibits virus replication. Angiotensin-converting-enzyme 2 (ACE2) in soluble form as a recombinant protein can prevent the spread of coronavirus by restricting binding and entry. In patients with COVID-19, hydroxychloroquine decreases the inflammatory response and cytokine storm, but overdose causes toxicity and mortality. Neuraminidase inhibitors such as oseltamivir, peramivir, and zanamivir are invalid for 2019-nCoV and are not recommended for treatment but protease inhibitors such as lopinavir/ritonavir (LPV/r) inhibit the progression of MERS-CoV disease and can be useful for patients of COVID-19 and, in combination with Arbidol, has a direct antiviral effect on early replication of SARS-CoV. Ribavirin reduces hemoglobin concentrations in respiratory patients, and remdesivir improves respiratory symptoms. Use of ribavirin in combination with LPV/r in patients with SARS-CoV reduces acute respiratory distress syndrome and mortality, which has a significant protective effect with the addition of corticosteroids. Favipiravir increases clinical recovery and reduces respiratory problems and has a stronger antiviral effect than LPV/r. currently, appropriate treatment for patients with COVID-19 is an ACE2 inhibitor and a clinical problem reducing agent such as favipiravir in addition to hydroxychloroquine and corticosteroids.

COVID-19 is now pandemic throughout the world. Scientist, doctors are searching for effective therapy of this diseases. The remdesivir, an antiviral drug, is appeared as 'molecule of hope' for the treatment of this disease. USFDA gave emergency approval to this drug for the treatment of COVID-19. The molecular mechanism is unknown. In this paper, we tried to describe the probable molecular mechanism of remdesivir to inhibit the RNA synthesis of SARS-CoV-2. However, more detail mechanism is needed to understand mechanism of action of remdesivir.

Remdesivir in the treatment of coronavirus disease 2019 (COVID-19): a simplified summary

The pandemic of COVID-19 (Coronavirus Disease-2019) is an extremely contagious respiratory illness due to a novel coronavirus, SARS-CoV-2. Certain drugs have several protein targets and many illnesses share overlapping molecular paths. In such cases, reusing drugs for more than one objective and finding their novice uses can considerably decrease the time in finding new cures for unforeseen diseases. Remdesivir has been recently a strong candidate for the treatment of Covid-19. In this commentary, we have portrayed the structure of the coronavirus in a simple way as well as the site where remdesivir acts. We have also displayed the ongoing clinical trials, as well as a published study that was conducted on compassionate base. The covid-19 pandemic might wean down by the end of summer 2020, but the risk of seasonality exists. Therefore, future disposal of agents such as remdesivir might be crucial for ensuring an efficient treatment, decrease mortality and allow early discharge. Communicated by Ramaswamy H. Sarma

Possible therapeutic agents for COVID-19: a comprehensive review

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged in China. There are no available vaccines or antiviral drugs for COVID-19 patients. Herein, we represented possible therapeutic agents that may stand as a potential therapy against COVID-19. AREAS COVERED: We searched PubMed, Google Scholar, and clinicaltrials.gov for relevant papers. We showed some agents with potentially favorable efficacy, acceptable safety as well as good pharmacokinetic profiles. Several therapies are under assessment to evaluate their efficacy and safety for COVID-19. However, some drugs were withdrawn due to their side effects after demonstrating some clinical efficacy. Indeed, the most effective therapies could be organ function support, convalescent plasma, anticoagulants, and immune as well as antiviral therapies, especially anti-influenza drugs due to the similarities between respiratory viruses regarding viral entry, uncoating, and replication. We encourage giving more attention to favipiravir, remdesivir, and measles vaccine. EXPERT OPINION: A combination, at least dual or even triple therapy, of the aforementioned efficacious and safe therapies is greatly recommended for COVID-19. Further, patients should have a routine assessment for their coagulation and bleeding profiles as well as their inflammatory and cytokine concentrations.

Antiviral treatment of COVID-19

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

A systematic review of convalescent plasma treatment for COVID19

Background. Transfusion of convalescent immune plasma (CP) is commonly used in epidemics. Several articles now describe clinical report data of CP for treatment of SARS-CoV-2-induced COVID-19 disease. Methods. A systematic literature review was conducted using the NCBI curated COVID-19 related open-resource literature database LitCovid to identify studies using CP as treatment for COVID-19 patients. We retrieved and curated all COVID-19 related patient and treatment characteristics from previously reported studies. A Poisson model was developed to evaluate the association between age of the patients, older age being the most common risk factor for COVID-19 mortality, and recovery time since CP treatment using data extracted from the literature. Results. From 18,293 identified COVID-19 related articles, we included ten studies reporting results of CP treatment for COVID-19 from a total of 61 patients. Decreased symptoms of severe COVID-19 and clearance of SARS-CoV-2 RNA were the most direct observations. We found that patients over the age of sixty who received CP treatment for COVID-19 had a significantly prolonged recovery estimated by viral clearance (from 10 to 29 days since first dose of CP) compared to younger patients, who recovered from the infection in less than a week after receiving CP treatment. Conclusions. Limited published results on plasma transfusion treatment for COVID-19 disease with concomitant treatments suggest that CP therapy for COVID-19 is well tolerated and effective. First randomized clinical trial results, however, reveal no improvements in recovery time for elderly patients with severe COVID-19 between standard treatment alone and added with convalescent plasma. Accordingly, we argue that older patients may need a significantly longer time for recovery. Further randomized clinical trial data for COVID-19 with rigorous ethical standards is urgently needed.

Old and re-purposed drugs for the treatment of COVID-19.

Introduction: The coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed since December 2019. It has caused a global pandemic with more than three hundred thousand case fatalities. However, apart from supportive care by respirators, no standard medical therapy is validated.Areas covered: This paper presents old drugs with potential in vitro efficacy against SARS-CoV-2. The in vitro database, adverse effects, and potential toxicities of these drugs are reviewed regarding their feasibility of clinical prescription for the treatment of patients with COVID-19. To obtain convincing recommendations, we referred to opinions from the US National Institute of Health regarding drugs repurposed for COVID-19 therapy.Expert opinion: Although strong evidence of well-designed randomized controlled studies regarding COVID-19 therapy is presently lacking, remdesivir, teicoplanin, hydroxychloroquine (not in combination with azithromycin), and ivermectin might be effective antiviral drugs and are deemed promising candidates for controlling SARS-CoV-2. In addition, tocilizumab might be considered as the supplementary treatment for COVID-19 patients with cytokine release syndrome. In future, clinical trials regarding a combination of potentially effective drugs against SARS-CoV-2 need to be conducted to establish the optimal regimen for the treatment of patients with moderate-to-severe COVID-19.

Antiviral treatment of COVID-19

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

Remdesivir investigational trials in COVID-19: a critical reappraisal

Abstract During outbreak of emerging disease, the most important aim is to discover an effective drug to save life. Consequently, a lot of effort are generally made by the industry to promote clinical trials with new drugs. Here we review evidence of the 8 most recent reports including 3 randomized controlled trials on the clinical efficacy of remdesivir in treating COVID-19 patient. We conclude that it is far too premature to identify remdesivir as a curative or life-saving intervention.

Have we found the panacea to COVID-19 with remdesivir, an old but newly packaged drug?

Clinical features of covid-19

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.

Old and re-purposed drugs for the treatment of COVID-19

INTRODUCTION: The coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed since December 2019. It has caused a global pandemic with more than three hundred thousand case fatalities. However, apart from supportive care by respirators, no standard medical therapy is validated. AREAS COVERED: This paper presents old drugs with potential in vitro efficacy against SARS-CoV-2. The in vitro database, adverse effects, and potential toxicities of these drugs are reviewed regarding their feasibility of clinical prescription for the treatment of patients with COVID-19. To obtain convincing recommendations, we referred to opinions from the US National Institute of Health regarding drugs repurposed for COVID-19 therapy. EXPERT OPINION: Although strong evidence of well-designed randomized controlled studies regarding COVID-19 therapy is presently lacking, remdesivir, teicoplanin, hydroxychloroquine (not in combination with azithromycin), and ivermectin might be effective antiviral drugs and are deemed promising candidates for controlling SARS-CoV-2. In addition, tocilizumab might be considered as the supplementary treatment for COVID-19 patients with cytokine release syndrome. In future, clinical trials regarding a combination of potentially effective drugs against SARS-CoV-2 need to be conducted to establish the optimal regimen for the treatment of patients with moderate-to-severe COVID-19.

Remdesivir in treatment of COVID-19: A systematic benefit-risk assessment

Background: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit-risk assessment was designed and conducted to strengthen the ongoing understanding of the benefit-risk balance for remdesivir in COVID-19 treatment by using a structured method which uses all available data. Methods: The Benefit-Risk Action Team (BRAT) framework was used to assess the overall benefit-risk of the use of remdesivir as a treatment for COVID-19 compared to standard of care, placebo or other treatments. We searched PubMed,Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. Results: Several key benefits and risks for use of remdesivir in COVID-19 compared to placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR=1.23, 95% CI: 0.87, 1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) comparted to the placebo group (26%), however more patients in the remdesivir group discontinued treatment as a result of an adverse event compared to those patients receiving placebo (12% vs 5%). Conclusions: Preliminary clinical trial results suggest a favourable benefit-risk profile for remdesivir compared to placebo, however there is limited safety data available at the current time. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit-risk assessment.

Use of herbal drugs to treat COVID-19 should be with caution

Mild or Moderate Covid-19

Successful treatment of patients severely ill with COVID-19.

Remdesivir (GS-5734), a viral RNA-dependent RNA polymerase (RdRP) inhibitor that can be used to treat a variety of RNA virus infections, is expected to be an effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. On May 1, 2020, The U.S. Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for remdesivir to treat COVID-19 patients. In light of the COVID-19 pandemic, this review presents comprehensive information on remdesivir, including information regarding the milestones, intellectual properties, anti-coronavirus mechanisms, preclinical research and clinical trials, and in particular, the chemical synthesis, pharmacology, toxicology, pharmacodynamics and pharmacokinetics of remdesivir. Furthermore, perspectives regarding the use of remdesivir for the treatment of COVID-19 are also discussed.

Antivirals for COVID-19.

Drugs targeting RNA respiratory viruses has resulted in few effective therapies, highlighting challenges for antivirals to treat COVID-19. Several antivirals are being investigated for symptomatic COVID-19 but no definitive data support their clinical use. Remdesivir, with good in vitro activity against SARS-CoV2, appeared to result in favorable outcomes for hospitalized patients in a compassionate use series with shortened time to recovery and a modest decrease in mortality. Currently, remdesivir is available in phase III clinical trials, the compassionate use program, and eventually through the emergency use authorization. A randomized controlled trial of lopinavir/ritonavir demonstrated no apparent clinical or virologic benefit and drug-drug interactions and side effects further limit its utility. Antivirals to treat influenza (oseltamivir) have limited activity against SARS-CoV-2, but favipiravir and umifenovir, influenza antivirals available internationally, have distinct viral targets and require further investigation. Antivirals with evidence of clinical activity must be studied as treatment and prophylaxis for those at high risk for severe COVID-19.

Suggestions for Combatting COVID-19 by Natural Means in the Absence of Standard Medical Regimens

Drug repurposing against COVID-19: focus on anticancer agents

BACKGROUND: The very limited time allowed to face the COVID-19 pandemic poses a pressing challenge to find proper therapeutic approaches. However, synthesis and full investigation from preclinical studies to phase III trials of new medications is a time-consuming procedure, and not viable in a global emergency, such as the one we are facing. MAIN BODY: Drug repurposing/repositioning, a strategy effectively employed in cancer treatment, can represent a valid alternative. Most drugs considered for repurposing/repositioning in the therapy of the COVID-19 outbreak are commercially available and their dosage and toxicity in humans is well known, due to years (or even decades) of clinical use. This can allow their fast-track evaluation in phase II-III clinical trials, or even within straightforward compassionate use. Several drugs being re-considered for COVID-19 therapy are or have been used in cancer therapy. Indeed, virus-infected cells are pushed to enhance the synthesis of nucleic acids, protein and lipid synthesis and boost their energy metabolism, in order to comply to the "viral program". Indeed, the same features are seen in cancer cells, making it likely that drugs interfering with specific cancer cell pathways may be effective as well in defeating viral replication. SHORT CONCLUSION: To our knowledge, cancer drugs potentially suitable for facing SARS-CoV-2 infection have not been carefully reviewed. We present here a comprehensive analysis of available information on potential candidate cancer drugs that can be repurposed for the treatment of COIVD-19.

Traditional Chinese medicine played a crucial role in battling COVID-19

A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir.

Rapid review for the anti-coronavirus effect of remdesivir.

The outbreak of SARS-CoV-2 rapidly spread across China and worldwide. Remdesivir had been proposed as a promising option for treating coronavirus disease 2019 (COVID-19). We provided a rapid review to critically assess the potential anti-coronavirus effect of remdesivir on COVID-19 and other coronaviruses based on the most up-to-date evidence. Even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well-designed and adequately-powered clinical trials for further clarification.