Remdesivir, ECMO, recommendations on convalescent plasma in COVID-19

Remdesivir had no significant effect on ventilated COVID-19 patients and a small effect on other hospitalized patients, according to a final analysis from the Solidarity trial published by The Lancet on May 2. The international trial included 8,275 hospitalized patients who were randomized to either 10 daily infusions (unless discharged earlier) or control. Overall mortality rates were insignificantly different at 14.5% in the remdesivir group and 15.6% in controls; in patients who were already on ventilation at randomization, rates were 42.1% and 38.6%, respectively. Among patients on supplemental oxygen, but not ventilation, 14.6% of those on remdesivir died versus 16.3% of controls (rate ratio [RR], 0.87 [95% CI, 0.76 to 0.99]; P=0.03). Among patients not on oxygen, rates were 2.9% and 3.8%, respectively (RR, 0.76 [95% CI, 0.46 to 1.28]; P=0.30). When all those not ventilated initially were combined, the mortality rate was 11.9% versus 13.5% (RR, 0.86 [95% CI, 0.76 to 0.98]; P=0.02) and progression to ventilation was 14.1% versus 15.7% (RR, 0.88 [95% CI, 0.77 to 1.00]; P=0.04). The authors also noted that allocation to daily remdesivir infusions delayed discharge by about a day.

“An anti-viral treatment that reduces time to recovery in lower-risk inpatients might have little effect on overall inpatient mortality, because this outcome is driven chiefly by dysregulated immune responses,” the study authors said. “Regardless of how these findings are interpreted, better drugs to treat COVID-19 will continue to be needed. Oral antiviral agents, various immune modulators, and monoclonal antibodies against currently circulating variants of concern are now emerging that might prove more effective, more convenient, or less expensive than daily remdesivir infusions, but large-scale randomised evidence will be needed to evaluate and compare them.”

An analysis of extracorporeal membrane oxygenation (ECMO), published by The BMJ on May 4, found that it improved mortality in patients with respiratory failure due to COVID-19. The international observational study included a total of 7,345 ICU patients, 11.5% of whom received ECMO at any time point during follow-up. Adherence-adjusted mortality was 26.0% (95% CI, 24.5% to 27.5%) for patients treated with ECMO if partial pressure of arterial oxygen to fraction of inspired oxygen (PaO₂/FiO₂) decreased below 80 mm Hg compared with 33.2% (95% CI, 31.8% to 34.6%) in patients treated without ECMO (risk difference, –7.1% [95% CI, −8.2% to –6.1%]; risk ratio, 0.78 [95% CI, 0.75 to 0.82]). Secondary analyses showed ECMO to be most effective in patients younger than age 65 years and with a PaO₂/FiO₂ below 80 mm Hg or driving pressures greater than 15 cm H₂O during the first 10 days of mechanical ventilation. The authors concluded that ECMO was associated with lower mortality in selected COVID-19 patients and that age, severity of hypoxemia, and duration and intensity of mechanical ventilation should be considered when deciding to initiate this intervention.

The NIH's COVID-19 Treatment Guidelines Panel made several updates on April 29, including changes to recommendations about the use of convalescent plasma. The panel now recommends against the use of plasma that was collected prior to the emergence of the omicron variant. They also recommend against its use in hospitalized, immunocompetent patients. There is insufficient evidence to recommend either for or against the use of high-titer convalescent plasma that was collected after the emergence of omicron for the treatment of immunocompromised patients or nonhospitalized, immunocompetent patients with COVID-19, the panel said.