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Ansems K, Grundeis F, Dahms K, et al. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2021;8:CD014962. Published 2021 Aug 5. doi:10.1002/14651858.CD014962.

Study Population: 7,452 adult patients with SARS-CoV-2 (hospitalized, moderately to severely ill) enrolled from 5 RCTs comparing remdesivir use to placebo or standard of care

Efficacy Endpoints

All-cause mortality up to day 28 after treatment, need for respiratory support (high-flow oxygen, non-invasive or invasive ventilation), duration to liberation from invasive mechanical ventilation at up to day 28, quality of life, duration of hospitalization, Intensive Care Unit (ICU) admission, and ICU stay duration

Harm Endpoints

Any adverse events up to day 28 after treatment

Narrative

The COVID-19 pandemic has, to date, infected over 230 million people and caused over 4.7 million deaths worldwide.1 There has been great urgency to identify effective treatments, including antiviral medications, to decrease morbidity and mortality. Remdesivir is an antiviral drug that has been hypothesized to inhibit viral replication of RNA viruses2 such as SARS-CoV-2.

The systematic review by Ansems et al3 that we summarize here identified five randomized controlled trials including 7,452 participants (mean age 59 years; hospitalized with moderate to severe illness, most requiring low-flow oxygen or mechanical ventilation at baseline; conducted in high or upper-middle income countries). Pooled data across the five studies found moderate certainty4 evidence that remdesivir treatment of COVID-19 patients resulted in no statistically significant difference in all-cause mortality at up to 28 days after treatment when compared to placebo or standard of care.

Remdesivir did not reduce the need for overall respiratory support (high-flow oxygen, invasive ventilation, or non-invasive ventilation) and had no effect on the duration of invasive mechanical ventilation. However, the certainty of evidence was low to very low. Although remdesivir reduced the need for new invasive mechanical ventilation within 28 days when compared to placebo or standard care (relative risk: 0.56, 95% CI 0.41 to 0.77; Absolute risk difference: 6.7%; number-needed-to treat: 15), the certainty of evidence was low. Therefore, we did not report this finding in the summary table. In general, the certainty of the data for the outcomes of need for any specific type of respiratory support and duration of invasive mechanical ventilation was low or very low. No studies measured quality of life, need for ICU admission, or duration of ICU stay.

The safety data were inconsistently reported in the original trials. Appropriately, the systematic review reported that the data on whether remdesivir increases or decreases adverse events was inconclusive, being comprised of very low-certainty evidence.

Caveats

The existing evidence has significant limitations. Ansems et al downgraded the certainty of evidence for the outcome of mortality from high to moderate due to concern for the failure of randomization in one of the included studies.5 For the outcomes of clinical improvement and adverse events, the authors downgraded the level of certainty due to limitations in the reported data. They cited missing data regarding the competing risks of death. For example, duration of mechanical ventilation would be reduced if a patient died. Another limitation was open-label design that was employed by one of the as included trials.6

Included RCTs used different scales for determining the disease severity and progression, as there are no standardized guidelines for determining 'moderate' and 'severe' severity of disease related to SARS-CoV-2. The need for respiratory support, and specifically, the need for each method of respiratory support (high-flow oxygen, non-invasive ventilation, and invasive ventilation) is also determined by clinical judgment and subject to significant variability.

Despite the significant limitations in regards to the study population, relative homogeneity of institutions, and risk of bias, the Cochrane review by Ansems et al3 is the largest and most recent review that included only randomized controlled trials comparing remdesivir to placebo or standard of care.

In summary, we assign a color recommendation of Yellow (unclear if benefits/more data needed) for the use of remdesivir in patients hospitalized for SARS-CoV-2. Additional data are needed to clarify the efficacy and safety of remdesivir for SARS-CoV-2 treatment. Further studies are also needed to address the efficacy and safety in different population subgroups (e.g. age, disease severity, timing of treatment administration, etc.) and socioeconomic settings.

The original manuscript was published in Medicine by the Numbers, American Family Physician as part of the partnership between TheNNT.com and AFP.

Author

Robert Allen, MD; Matthew Turner, MD; Ian S. deSouza, MD
Supervising Editors: Shahriar Zehtabchi, MD; Dan Runde, MD

Published/Updated

October 12, 2021