Remdesivir Treatment in Patients Hospitalized with COVID-19: A Comparative Analysis of In-Hospital All-Cause Mortality

ABSTRACT

Background. Remdesivir (RDV) reduced time to recovery and mortality in some subgroups of hospitalized patients in the NIAID ACTT-1 RCT compared to placebo. Comparative effectiveness data in clinical practice are limited. Methods. Using the Premier Healthcare Database, we compared survival for adult non-mechanically ventilated hospitalized COVID-19 patients between Aug-Nov 2020 and treated with RDV within 2 days of hospitalization vs. those who did not receive RDV. Preferential within-hospital propensity score matching with replacement was used. Patients were matched on baseline O2 and 2-month admission period and were excluded if discharged within 3 days of RDV initiation (to exclude anticipated discharges/transfers within 72 hrs consistent with ACTT-1 study). Time to 14- and 28-day mortality was examined separately for patients on high-flow/non-invasive ventilation (NIV), low-flow, and no supplemental O2 using Cox Proportional Hazards models. Results. RDV patients (n=27,559) were matched to unique non-RDV patients (n=15,617) (Fig 1). The two groups were balanced;median age 66 yrs and 73% white (RDV);68 yrs and 74% white (non-RDV), and 55% male. At baseline, 21% required high-flow O2, 50% low-flow O2, and 29% no O2, overall. Mortality in RDV patients was 9.6% and 13.8% on days 14 and 28, respectively. For non-RDV patients, mortality was 14.0% and 17.3% on days 14 and 28, respectively. Kaplan-Meier curves for time to mortality are shown in Fig 2. After adjusting for baseline and clinical covariates, RDV patients on no O2 and low-flow O2 had a significantly lower risk of death within 14 days (no O2, HR 0.69, 95% CI 0.57-0.83;low-flow, HR 0.67, 95% CI 0.59-0.77) and 28 days (no O2, HR 0.80, 95% CI 0.68-0.94;low-flow, HR 0.76, 95% CI 0.68-0.86). Additionally, RDV patients on high-flow O2/NIV had a significantly lower risk of death within 14 days (HR 0.81, 95% CI 0.70-0.93);but not at 28 days (Fig 3). Conclusion. In this large study of patients in clinical care hospitalized with COVID-19, we observed a significant reduction of mortality in RDV vs. non-RDV treated patients in those on no O2 or low-flow O2. Mortality reduction was also seen in patients on high-flow O2 at day 14, but not day 28. These data support the use of RDV early in the course of COVID-19 in hospitalized patients.