Remdesivir use in patients with coronavirus COVID-19 disease: a systematic review and meta-analysis of the Chinese Lancet trial with the NIH trial

Alexander, Paul; Piticaru, Joshua; Lewis, Kimberley; Aryal, Komal; Thomas, Priya; Szczeklik, Wojciech; Fronczek, Jakub; Polok, Kamil; Alhazzani, Waleed; Mammen, Manoj J.

doi:10.1101/2020.05.23.20110932

Cited by 14 publications

(23 citation statements)

References 20 publications

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“…Taking into account that the study was not powered to evaluate mortality, this is still a positive signal that must be further evaluated in large-scale studies. A meta-analysis with pooled data from the two available RCTs that is still under peer review concludes a statistically significant reduction in mortality (risk ratio [RR], 0.69 [95% CI, 0.49 to 0.99]) ( 71 ). Although the clinical data on remdesivir are not fully published yet, the emergency authorizations and recent approval by the EMA are encouraging, as most other investigational drugs have failed until now ( 72 , 73 ), leaving remdesivir the only antiviral with clinically proven efficacy against COVID-19 to date.…”

Section: Discussionmentioning

confidence: 99%

Remdesivir against COVID-19 and Other Viral Diseases

et al. 2020

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SUMMARY Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. In vivo, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.

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Section: Discussionmentioning

confidence: 99%

Remdesivir against COVID-19 and Other Viral Diseases

et al. 2020

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“…Compared with the previous meta-analysis, we included more studies to assess clinical efficacy [4]. Since the studies involved patients of different baseline ordinal score, the effects may vary across individuals.…”

Section: Discussionmentioning

confidence: 99%

“…Its therapeutic effects, adverse events and usage in COVID-19 patients are currently being explored in large-scale randomized controlled trials (RCTs). A recent meta-analysis in a preprint format has only included two RCTs [4]. We aimed to provide a more up-to-date systematic review and meta-analysis to investigate the therapeutic effect and adverse events of remdesivir in severe COVID-19 infections with existing literature to date.…”

Section: Introductionmentioning

confidence: 99%

Remdesivir for the Treatment of Severe SARS-CoV-2 (COVID-19): A Systematic Review and Meta-Analysis

Yan¹,

Cheung²,

Lau³

et al. 2020

RGM

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Background: Coronavirus Disease in 2019 (COVID-19) is a pandemic caused by SARS-CoV-2 infection. Over 53 million people have been infected with over 1.3 million deaths. However, there is no standard treatment or vaccines to date. Recently, several randomized controlled trials and cohort studies have demonstrated the efficacy of remdesivir for the treatment of severe COVID-19 patients. This is a systematic review and meta-analysis to define its efficacy. Methods: A systematic review was done on databases (PubMed, Embase, Medline, Cochrane) on 9 Nov 2020. Search keywords were remdesivir, COVID-19, SARS-CoV-2, randomized controlled trials and cohort studies. Studies with high-evidence values were selected to evaluate its clinical efficacy in terms of risk ratio, time to clinical improvement, and mortality risk. Subgroup analysis was performed based on baseline hospitalization status, age and ethnicity. Results: Of the 1328 studies, 6 studies were selected and pooled for meta-analysis. Remdesivir was associated with clinical improvement (risk ratio 1.14, 95% CI 1.02-1.28, p=0.02). It shortened the mean time of clinical improvement by 3.32 days (95% CI -4.37 to -2.28, p<0.001). However, its use was not associated with reduced mortality risk (risk ratio 0.75, 95% CI 0.40–1.40). In subgroup analysis, remdesivir was associated with clinical improvement in patients without the need of invasive ventilation (risk ratio 1.90, 95% CI 1.58-2.29, p<0.001; hazard ratio 2.22, 95% CI, 1.64-3.02), and age less than 70 years (risk ratio 2.14, 95% CI 1.39-3.28, p<0.001). Conclusion: Remdesivir is effective in the treatment of severe COVID-19 patients, in particular those without invasive ventilation

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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%

“…Due to the lack of such studies, the authors also stated that remdesivir should not be recommended for the treatment of severe COVID‐19. A third review of pooled evidence from 1141 COVID‐19 patients 287 noted that remdesivir has a modest yet significant reduction in mortality (0.67, 95% CI 0.47–0.96) and significantly improves the time to recovery (3.95 less days, for 3.86 less days to 4.05 less days). The authors concluded that remdesivir may not be sufficient on its own, but in combination with other antivirals or with convalescent plasma may be sufficiently effective 287 .…”

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

confidence: 99%

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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Remdesivir use in patients with coronavirus COVID-19 disease: a systematic review and meta-analysis of the Chinese Lancet trial with the NIH trial

Cited by 14 publications

References 20 publications

Remdesivir against COVID-19 and Other Viral Diseases

Remdesivir against COVID-19 and Other Viral Diseases

Remdesivir for the Treatment of Severe SARS-CoV-2 (COVID-19): A Systematic Review and Meta-Analysis

Pathogenesis‐directed therapy of 2019 novel coronavirus disease

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