Remdesivir cuts mortality in COVID-19 patients requiring no or low-flow oxygen

In a systematic review and individual patient data meta-analysis, the broad-spectrum antiviral agent remdesivir reduced mortality in adult patients hospitalized for COVID-19 who did not require oxygen support or only required low-flow supplementation when the need for oxygen arose.

“Our results show significant survival benefit from remdesivir and less progression to mechanical ventilation or death in [hospitalized COVID-19] patients with no or conventional oxygen support,” said the researchers.

Individual data were provided for eight of the nine eligible randomized controlled trials (n=10,480; median age 58 years, 63 percent male). More than half of participants had at least one comorbidity. All were unvaccinated. After a median symptom duration of 9 days, participants were randomized to receive either remdesivir or usual care (as defined by the local context) with or without placebo. About 16 percent of participants received noninvasive or mechanical ventilation at baseline. [Lancet Respir Med 2023;S2213-2600(22)00528-8]

After adjusting for covariates*, fewer deaths within 28 days of randomization were reported with remdesivir than with usual care (12.5 percent vs 14.1 percent; adjusted odds ratio [adjOR], 0.88; p=0.045). A similar effect was seen in the subgroup of participants who received no or low-flow oxygen (9.1 percent vs 11.2 percent; adjOR, 0.80; p_interaction=0.019 [high-certainty evidence]).

Secondary endpoints

At day 60, all-cause mortality rate remained lower in the remdesivir compared with the usual care arm (13.7 percent vs 15.2 percent; adjOR, 0.91; p=0.116).

The remdesivir arm also had fewer patients requiring new mechanical ventilation or dying at day 28 (18.5 percent vs 22.3 percent; adjOR, 0.81; p<0.0001) and more mechanical ventilation-free days within 28 days (adjusted incidence rate ratio, 1.05; p<0.0001) than the usual care arm.

Patients on remdesivir had better clinical status on an ordinal scale – ie, less respiratory support at day 14 (adjOR, 0.88; p=0.0015) and day 28 (adjOR, 0.87; p=0.0037) than those in the usual care arm.

A grade 3/4 or serious adverse event was less likely to occur within the first 28 days among patients receiving remdesivir as opposed to those receiving usual care (27.3 percent vs 32.3 percent; adjOR, 0.86; p=0.046).

Of those who were receiving oxygen at baseline, time to oxygen cessation within 28 days was 2 days shorter with remdesivir than with usual care (11 vs 13 days; adjusted hazard ratio, 1.13; p=0.0042).

Inconclusive data on ventilated patients

Results were inconclusive for individuals who were receiving high-flow oxygen, non-invasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (30 percent vs 28.5 percent; adjOR, 1.10). “[In this subgroup,] remdesivir might have little or no effect on day-28 mortality,” the researchers explained.

However, they noted that this could have been driven by the small size of this subgroup. The evidence was also deemed ‘low-certainty’. “The effect size of remdesivir in patients with more respiratory support … remains to be further elucidated,” they said. “Their treatment should therefore be individualized.”

Aligns with current guidelines

“[Taken together,] our findings are in line with the IDSA** guidelines and the most recent update of the WHO COVID-19 treatment guidelines, both of which recommend using remdesivir for patients with severe but not critical COVID-19,” said the researchers. [www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management; BMJ 2020;370:m3379]

Further studies are also warranted to shed light on the effect of remdesivir on patients who have completed their COVID-19 vaccination doses, received their booster dose/s, or those who have pre-existing immunity from previous infection, they added.