Effect of Remdesivir on Mortality in Mechanically Ventilated COVID-19 Patients: A Target Trial Emulation Using...

The efficacy of remdesivir in critically ill COVID-19 patients requiring mechanical ventilation remains controversial. Although current guidelines recommend against routine use in this population, clinical practice varies. We evaluated the association between remdesivir and mortality using a target trial emulation framework.

This retrospective cohort study included adult COVID-19 patients requiring endotracheal intubation within 7 days of diagnosis at a tertiary medical center in Taiwan (January 2021-March 2024). Remdesivir exposure was defined as in-hospital initiation of standard-dose remdesivir within 3 days of COVID-19 diagnosis (the grace period; diagnosis date defined as time zero), continued for at least 3 consecutive days. Stabilized inverse probability of treatment weighting (S-IPTW) using 15 baseline covariates was applied. Primary outcomes were overall and 90-day mortality; secondary outcome was mechanical ventilation duration.

Among 163 eligible patients, 117 (71.8%) received remdesivir. After S-IPTW weighting, covariates were well balanced (maximum |SMD|=0.148). Remdesivir was associated with increased overall mortality (HR 2.52; 95% CI 1.24-5.15; p=0.011) and prolonged mechanical ventilation (HR 2.79; 95% CI 1.37-5.68; p=0.005). A similar trend was observed for 90-day mortality (HR 2.09; 95% CI 0.97-4.48; p=0.060). Findings were consistent after excluding ECMO users (overall mortality HR 2.68; 95% CI 1.27-5.62; p=0.009). E-values suggested moderate robustness to unmeasured confounding.

In mechanically ventilated COVID-19 patients, remdesivir use was associated with, but not proven to cause, increased mortality and longer ventilation duration; these observational findings align with guideline recommendations against routine initiation in this setting.