Overview: Remdesivir and long-term outcomes after COVID-19 hospitalization
Remdesivir (RDV) has been evaluated for short-term benefits in both hospitalized and non-hospitalized patients with COVID-19. However, its impact on long-term outcomes, particularly for patients who survive the initial hospitalization, has been less clear. A real-world study across three health systems in Colorado and Utah examined whether receiving RDV during hospitalization was associated with reduced mortality after discharge. The findings suggest a notable association between inpatient RDV treatment and lower all-cause mortality during extended follow-up, up to two and a half years later.
Study design and population
The analysis used an observational cohort drawn from electronic health records (EHRs) linked with state vaccination and mortality data. The primary cohort included adults hospitalized with COVID-19 between November 2020 and October 2022 who survived index hospitalization and were discharged. After exclusions (including those who died in hospital and those who received outpatient antivirals), the final sample comprised 9,760 patients, with 4,771 treated with inpatient remdesivir (IP RDV) and 4,989 not treated.
Researchers employed Cox proportional hazards models to estimate the risk of all-cause mortality after discharge, adjusting for a wide range of pre-hospital and in-hospital factors. They also conducted sensitivity analyses, including propensity-matching with in-hospital mortality as a competing risk, to address potential biases.
Key findings: long-term mortality and other post-discharge outcomes
The primary finding was that inpatient RDV was associated with a reduced hazard of post-discharge mortality among survivors. The adjusted hazard ratio was 0.73 (95% CI 0.61–0.87), indicating a meaningful decrease in long-term mortality risk for those treated with RDV during their index hospitalization. This protective effect persisted in several sensitivity analyses, including a competing-risk model that treated in-hospital death as a competing outcome (aHR 0.76; CI 0.63–0.92).
Secondary outcomes also favored RDV: reductions in 28-day post-discharge re-hospitalization (aHR 0.77; CI 0.67–0.89) and 28-day post-discharge ED visits (aHR 0.79; CI 0.67–0.92). Subgroup analyses suggested most patients benefited, including those who required oxygen during their hospitalization, though certain groups—such as those infected during the first Omicron wave, those who had at least one vaccine dose, and patients not needing supplemental oxygen—showed varying degrees of benefit. There were hints that the mortality benefit might be more pronounced over time, with cumulative hazard differences widening as follow-up continued.
Possible explanations and interpretation
The study does not prove causation, but several hypotheses may explain the association. RDV’s antiviral activity could promote viral clearance, reducing long-term viral reservoirs or ongoing inflammatory processes that contribute to adverse outcomes. An anti-inflammatory effect might also help mitigate cardiovascular risk linked to viral infections. The heterogeneity in effect by vaccination status suggests that unvaccinated individuals might gain more from inpatient RDV, while vaccine-induced immunity could alter the treatment’s relative impact.
Limitations and considerations for clinicians
Important caveats include the absence of corticosteroid use data and other in-hospital COVID-19 treatments in the analysis, which could influence mortality and other outcomes. Survivor bias is also possible since patients who died in the hospital were excluded from the primary cohort. The study could not assess the duration of RDV treatment or the timing of therapy initiation relative to symptom onset. Finally, residual differences in illness severity at discharge and post-discharge care levels were not fully captured, which may bias estimates.
Implications for practice and future research
These real-world findings support considering inpatient RDV as part of the treatment plan for eligible hospitalized COVID-19 patients, given the potential for reduced long-term mortality and fewer early post-discharge hospital visits. Prospective studies or randomized trials focusing on long-term outcomes and including detailed data on concurrent therapies, vaccination status, and markers of illness severity could help clarify causality and guide optimized treatment strategies for future variants.
