Overview
New real-world data from three health systems in Colorado and Utah suggest that receiving remdesivir (RDV) during a COVID-19–related hospitalization is associated with lower all-cause mortality after discharge. The study analyzed patients who survived their initial hospitalization and followed them for up to 29 months to assess long-term outcomes, including mortality, readmission to hospital, and emergency department (ED) visits.
What the study looked at
Researchers conducted a retrospective observational cohort study using electronic health records (EHRs) merged with state vaccination and mortality data. The primary cohort included adults (18+) who were hospitalized for COVID-19, survived to discharge, and did not receive outpatient antiviral treatments after discharge. After exclusions, the final analytic sample comprised 9,760 patients, of whom 4,771 (48.8%) received inpatient RDV during their index hospitalization.
The study applied unadjusted and adjusted Cox proportional hazards models to estimate the hazard of all-cause mortality after discharge, comparing those who received RDV to those who did not. Sensitivity analyses included propensity-matching and competing-risk models to account for in-hospital mortality as a competing event.
Key findings
Main result: In adjusted models, inpatient RDV use was associated with a reduced risk of post-discharge mortality (adjusted hazard ratio aHR 0.73; 95% CI 0.61–0.87) over follow-up extending up to about two and a half years. A competing-risk analysis for in-hospital mortality yielded a similar protective association (aHR 0.76; 95% CI 0.63–0.92).
RDV treatment was also linked to fewer post-discharge healthcare utilizations: reduced 28-day re-hospitalization (aHR 0.77; 95% CI 0.67–0.89) and fewer ED visits after discharge (aHR 0.79; 95% CI 0.67–0.92).
Subgroup analyses showed most groups benefited, with notable exceptions. The potential lack of RDV benefit appeared among patients infected during the first Omicron wave, those who had received at least one vaccine dose, and patients who did not require supplemental oxygen during the index hospitalization. Interactions suggested vaccination status and the level of respiratory support during the index hospitalization could influence RDV’s long-term effect.
Interpretation and possible mechanisms
Although the study cannot establish causation, the authors propose several hypotheses for the observed long-term benefit of RDV. The antiviral action may accelerate viral clearance, reduce ongoing viral reservoirs, or mitigate subclinical inflammation that contributes to cardiovascular risk after COVID-19. The interaction with vaccination status supports the idea that RDV’s relative benefit may be greater for unvaccinated individuals, potentially reflecting higher baseline risk in this subgroup.
Strengths and limitations
Strengths include a large, real-world, multi-system dataset with comprehensive mortality tracking and robust statistical approaches, including DAG-based covariate selection and multiple sensitivity analyses. Limitations include missing data on corticosteroid use and other in-hospital COVID-19 therapies, potential survivor bias from excluding in-hospital deaths, and lack of data on RDV treatment duration or exact timing relative to symptom onset. The follow-up period, while substantial, cannot capture very long-term outcomes beyond ~2.5 years.
Clinical implications
The findings suggest that RDV, when used during hospitalization for COVID-19, may confer a durability benefit extending beyond discharge for survivors. This could influence post-discharge risk stratification and follow-up planning, particularly for patients without full vaccination or those with higher pre-existing cardiovascular risk. However, given observational design and potential confounding, randomized trials or further prospective studies would help confirm causality and clarify mechanisms.
What remains to be explored
Future research should examine the impact of RDV duration and timing, interaction with corticosteroids and other in-hospital treatments, and the specific pathways by which RDV might reduce long-term mortality. Understanding the role of viral clearance versus inflammatory modulation could inform post-acute COVID-19 care strategies.
Bottom line
In this real-world analysis of three large health systems, inpatient remdesivir use among survivors of COVID-19 hospitalization was associated with reduced long-term mortality and fewer post-discharge hospital and ED visits, though results vary by patient subgroup and vaccination status. Ongoing investigation will help determine the consistency and mechanisms of these associations.
