Efficacy and harms of remdesivir for the treatment of COVID-19: a systematic review and meta-analysis

Piscoya, Alejandro; Ng-Sueng, Luis Fernando; Riego, Angela Parra del; Cerna-Viacava, Renato; Pasupuleti, Vinay; Roman, Yuani M.; Thota, Priyaleela; White, C Michael; Hernandez, Adrián V.

doi:10.1101/2020.05.26.20109595

Cited by 14 publications

(19 citation statements)

References 17 publications

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“…Additionally, Liu et al found in their SR and metanalyses that there was insufficient evidence that suggests any benefit from the treatments included (Lopinavir/Ritonavir, Ribavirin, Chloroquine, hydroxychloroquine, arbidol, favipiravir) in the clinical outcomes of the patients. Also, they found an increase in the GI adverse events with the use of Lopinavir/ritonavir [18].…”

Section: Discussionmentioning

confidence: 99%

Antiviral Treatment for COVID-19: A Systematic Review

Arias

Chavez

Panato

et al. 2020

JPRI

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Aim: In December 2019, there were reports of a new type of coronavirus that affects the different health systems of the world. We have carried out a systematic review of the possible antivirals studied that could be useful in this public health catastrophe. Data Sources: A search strategy with MESH terms was performed in PubMed, Web of Science, and Scopus. Also, RCTs published in clinicaltrials.gov were reviewed. The databases were searched between April and June 2020. Study Selection: We selected all Randomized Controlled Trials evaluating the effects of antivirals and 5 studies were included from a research database of 280 articles collected between. After removing duplicated articles, 43 were selected for review. Finally, 5 articles were eligible for full-text review and included in the article. Results: Current randomized controlled trial data showed no clinical improvement in terms of mortality, need for oxygen support or need for intubation in patients who used antivirals versus those who did not. No clinical improvement was demonstrated. It was observed that there is difficulty in calculating clinical improvement, this large difference makes the eligible studies difficult to compare. Conclusion: These predictors, however, need further work to validate reliability. More clinical trials involving antivirals are needed to observe a relationship between clinical improvement or mortality from SARS-CoV-19.

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Section: Discussionmentioning

confidence: 99%

Antiviral Treatment for COVID-19: A Systematic Review

Arias

Chavez

Panato

et al. 2020

JPRI

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“…Remdesivir has been shown to inhibit SARS‐CoV‐2 replication in human stem cell‐derived intestinal organoids 279 . This potent in vitro activity against SARS‐CoV‐2 has led to a number of clinical trials of intravenous remdesivir in adults hospitalized with COVID‐19 280–287 …”

Section: Therapy Of Sars‐cov‐2 Infections Based On the Pathogenesis Omentioning

confidence: 99%

“…The data from 1075 patients with COVID‐19 demonstrated that patients receiving remdesivir had a higher discharge rate (50.43% vs. 45.29%) and a lower mortality rate (8.2% vs. 12.7%) than patients in the placebo group 285 . Another similar study analyzed two randomized controlled trials ( n = 1300) and two observational studies ( n = 88) in which remdesivir 200 mg IV was given on the first day and 100 mg IV was given daily for 9 more days 286 . Remdesivir decreased the median time to recovery in one randomized controlled study but did not decrease the time to clinical treatment in the other randomized controlled study 286 .…”

Section: Therapy Of Sars‐cov‐2 Infections Based On the Pathogenesis Omentioning

confidence: 99%

“…Another similar study analyzed two randomized controlled trials ( n = 1300) and two observational studies ( n = 88) in which remdesivir 200 mg IV was given on the first day and 100 mg IV was given daily for 9 more days 286 . Remdesivir decreased the median time to recovery in one randomized controlled study but did not decrease the time to clinical treatment in the other randomized controlled study 286 . The authors concluded that there is a paucity of adequately powered and fully reported randomized controlled studies.…”

Section: Therapy Of Sars‐cov‐2 Infections Based On the Pathogenesis Omentioning

confidence: 99%

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Pathogenesis‐directed therapy of 2019 novel coronavirus disease

Stratton

Tang

2020

Journal of Medical Virology

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The 2019 novel coronavirus disease (COVID‐19) now is considered a global public health emergency. One of the unprecedented challenges is defining the optimal therapy for those patients with severe pneumonia and systemic manifestations of COVID‐19. The optimal therapy should be largely based on the pathogenesis of infections caused by this novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Since the onset of COVID‐19, there have been many prepublications and publications reviewing the therapy of COVID‐19 as well as many prepublications and publications reviewing the pathogenesis of SARS‐CoV‐2. However, there have been no comprehensive reviews that link COVID‐19 therapies to the pathogenic mechanisms of SARS‐CoV‐2. To link COVID‐19 therapies to pathogenic mechanisms of SARS‐CoV‐2, we performed a comprehensive search through MEDLINE, PubMed, medRxiv, EMBASE, Scopus, Google Scholar, and Web of Science using the following keywords: COVID‐19, SARS‐CoV‐2, novel 2019 coronavirus, pathology, pathologic, pathogenesis, pathophysiology, coronavirus pneumonia, coronavirus infection, coronavirus pulmonary infection, coronavirus cardiovascular infection, coronavirus gastroenteritis, coronavirus autopsy findings, viral sepsis, endotheliitis, thrombosis, coagulation abnormalities, immunology, humeral immunity, cellular immunity, inflammation, cytokine storm, superantigen, therapy, treatment, therapeutics, immune‐based therapeutics, antiviral agents, respiratory therapy, oxygen therapy, anticoagulation therapy, adjuvant therapy, and preventative therapy. Opinions expressed in this review also are based on personal experience as clinicians, authors, peer reviewers, and editors. This narrative review linking COVID‐19 therapies with pathogenic mechanisms of SARS‐CoV‐2 has resulted in six major therapeutic goals for COVID‐19 therapy based on the pathogenic mechanisms of SARS‐CoV‐2. These goals are listed below: The first goal is identifying COVID‐19 patients that require both testing and therapy. This is best accomplished with a COVID‐19 molecular test from symptomatic patients as well as determining the oxygen saturation in such patients with a pulse oximeter. Whether a symptomatic respiratory illness is COVID‐19, influenza, or another respiratory pathogen, an oxygen saturation less than 90% means that the patient requires medical assistance. The second goal is to correct the hypoxia. This goal generally requires hospitalization for oxygen therapy; other respiratory‐directed therapies such as prone positioning or mechanical ventilation are often used in the attempt to correct hypoxemia due to COVID‐19. The third goal is to reduce the viral load of SARS‐CoV‐2. Ideally, there would be an oral antiviral agent available such as seen with the use of oseltamivir phosphate for influenza. This oral antiviral agent should be taken early in the course of SARS‐CoV‐2 infection. Such an oral agent is not available yet. Currently, two options are available for reducing the viral load of SARS‐CoV‐2. These are post‐Covid‐1...

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“…Other systematic reviews found an increase in the risk of diarrhoea and nausea and/or vomiting with lopinavir-ritonavir 37,38 and hydroxychloroquine, [38][39][40] increase in arrhythmias and QTc interval prolongation with hydroxychloroquine alone, [40][41][42] or combined with a macrolide, 43,44 and no significant increase in renal failure with remdesivir. 45…”

Section: Strengths and Limitations Of This Reviewmentioning

confidence: 99%

Adverse effects of remdesivir, hydroxychloroquine, and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomized trials

Izcovich

Siemieniuk

Bartoszko

et al. 2020

Preprint

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IntroductionIn an attempt to improve outcomes for patients with coronavirus disease 19 (COVID-19), several drugs, such as remdesivir, hydroxychloroquine (with or without azithromycin), and lopinavir/ritonavir, have been evaluated for treatment. While much attention focuses on potential benefits of these drugs, this must be weighed against their adverse effects.MethodsWe searched 32 databases in multiple languages from 1 December 2019 to 27 October 2020. We included randomized trials if they compared any of the drugs of interest to placebo or standard care, or against each other. A related world health organization (WHO) guideline panel selected the interventions to address and identified possible adverse effects that might be important to patients. Pairs of reviewers independently extracted data and assessed risk of bias. We analyzed data using a fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the GRADE approach.ResultsWe included 16 randomized trials which enrolled 8226 patients. Compared to standard care or placebo, low certainty evidence suggests that remdesivir may not have an important effect on acute kidney injury (risk difference [RD] 8 fewer per 1000, 95% confidence interval (CI): 27 fewer to 21 more) or cognitive dysfunction/delirium (RD 3 more per 1000, 95% CI: 12 fewer to 19 more). Low certainty evidence suggests that hydroxychloroquine may increase the risk of serious cardiac toxicity (RD 10 more per 1000, 95% CI: 0 more to 30 more) and cognitive dysfunction/delirium (RD 33 more per 1000, 95% CI: 18 fewer to 84 more), whereas moderate certainty evidence suggests hydroxychloroquine probably increases the risk of diarrhoea (RD 106 more per 1000, 95% CI: 48 more to 175 more) and nausea and/or vomiting (RD 62 more per 1000, 95% CI: 23 more to 110 more) compared to standard care or placebo. Low certainty evidence suggests lopinavir/ritonavir may increase the risk of diarrhoea (RD 168 more per 1000, 95% CI: 58 more to 330 more) and nausea and/or vomiting (RD 160 more per 1000, 95% CI: 100 more to 210 more) compared to standard care or placebo.ConclusionHydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Remdesivir may have no effect on risk of acute kidney injury or cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19.

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Efficacy and harms of remdesivir for the treatment of COVID-19: a systematic review and meta-analysis

Cited by 14 publications

References 17 publications

Antiviral Treatment for COVID-19: A Systematic Review

Antiviral Treatment for COVID-19: A Systematic Review

Pathogenesis‐directed therapy of 2019 novel coronavirus disease

Adverse effects of remdesivir, hydroxychloroquine, and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomized trials

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