Remdesivir Linked to Lower Mortality in Patients with COVID-19 Requiring Supplemental Oxygen

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Remdesivir treatment is associated with significantly reduced mortality among patients hospitalized with COVID-19 requiring supplemental oxygen across SARS-CoV-2 variants of concern (VOC), report authors of a new study.

Researchers published their findings from the large, multicenter, retrospective cohort study in Open Forum Infectious Diseases, the journal of the Infectious Diseases Society of America.

“Although over 3 years have passed since the emergence of severe acute respiratory syndrome coronavirus 2, patients critically ill with COVID-19 still face high mortality rates and have limited therapeutic options,” wrote corresponding author Robert L. Gottlieb MD, PhD, deputy editor for Baylor University Medical Center Proceedings, and colleagues.

According to investigators, approximately 1 in 2 patients in the US with COVID-19 requiring invasive ventilation have died since the beginning of the COVID-19 pandemic.

“It remains essential to continue to evaluate therapeutic options to treat patients throughout the spectrum of COVID-19 disease and VOC periods,” stated Gottlieb and coauthors. “Remdesivir has maintained effective antiviral activity against all clinically relevant VOC and retains an important role in the management of COVID-19.”

Findings from previous randomized controlled trials—such as the Adaptive COVID-19 Treatment Trial (ACTT-1) and the SOLIDARITY trial—show that remdesivir use improves time to recovery and reduces mortality in patients hospitalized with COVID-19.

It is less clear, however, how effective remdesivir is for patients with COVID-19 who are critically ill, noted researchers. To gain insight, Gottlieb and colleagues matched patients who were hospitalized for COVID-19 between December 2020 and April 2022 and received remdesivir upon admission 1:1 to patients not given remdesivir while hospitalized with the virus.

Analyses were stratified by supplemental oxygen requirement upon admission—low-flow oxygen (LFO), high-flow oxygen/noninvasive ventilation (HFO/NIV), or invasive mechanical ventilation/extracorporeal membrane oxygenation (IMV/ECMO)—and VOC periods (pre-Delta, Delta-predominant, and Omicron-predominant).

“Cox proportional hazards models were used to derive adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for 14- and 28-day mortality,” stated authors.

According to the study, a total of 67 582 patients receiving LFO, 34 857 receiving HFO/NIV, and 4164 receiving IMV/ECMO, all treated with remdesivir, were matched to nonremdesivir-treated participants.

FINDINGS

Researchers observed that unadjusted mortality rates were significantly lower for patients treated with remdesivir at 14 days (LFO: 6.4% vs 8.8%; HFO/NIV: 16.8% vs 19.4%; IMV/ECMO: 27.8% vs 35.3%) and 28 days (LFO: 9.8% vs 12.3%; HFO/NIV: 25.8% vs 28.3%; IMV/ECMO: 41.4% vs 50.6%).

In adjusted analyses, remdesivir treatment was associated with a statistically significant reduction in in-hospital mortality at 14 days (LFO: aHR 0.79, 95% CI 0.66-0.79; HFO/NIV: aHR 0.83, 95% CI 0.77–0.89; IMV/ECMO: aHR 0.73, 95% CI 0.65–0.82) and 28 days (LFO: aHR 0.79, 95% CI 0.73–0.85; HFO/NIV: aHR 0.88, 95% CI 0.82–0.93; IMV/ECMO: aHR 0.74, 95% CI 0.67–0.82) compared with nonremdesivir treatment.

This lower risk of mortality among patients who received remdesivir was observed across the specified VOC periods, although researchers noted that the association was most pronounced during the Omicron wave.

“Where early remdesivir administration is not possible, robust findings from this study demonstrate that remdesivir administration is associated with a survival benefit even when the hyperinflammatory response has already developed as in patients requiring HFO/NIV or IMV/ECMO,” concluded Gottlieb et al. “Given the growing evidence supporting the clinical and survival benefits associated with remdesivir use in both severe and critically ill COVID-19 patients, clinical guidelines may merit further revisions.”

Source: Mozaffari E, Chandak A, Gottlieb RL, et al. Remdesivir is associated with reduced mortality in COVID-19 patients requiring supplemental oxygen including invasive mechanical ventilation across SARS-CoV-2 variants. Open Forum Infect Dis.2023;10(10):ofad482. doi:10.1093/ofid/ofad482.