Remdesivir and All-Cause Graft Loss Among Kidney Transplant Recipients With Symptomatic COVID-19

Importance: The efficacy and safety of remdesivir for COVID-19 in kidney transplant (KT) recipients across evolving pandemic eras remain unclear. Objective: To compare clinical outcomes among adult KT recipients with symptomatic COVID-19 who received early remdesivir vs those who did not receive remdesivir. Design, Setting, and Participants: This retrospective cohort study emulated a target trial using observational data from 5 hospitals within the Johns Hopkins Health System. Adult KT recipients (aged ≥18 years) with a functioning allograft and symptomatic COVID-19 from March 2020 through January 2024 were eligible. Patients who received anti-SARS-CoV-2 monoclonal antibodies, nirmatrelvir-ritonavir, and/or molnupiravir were excluded. Follow-up continued for up to 1 year after COVID-19 diagnosis. Exposures: Individuals who initiated remdesivir within 7 days of diagnosis and received at least 3 consecutive days of therapy were assigned to the early remdesivir strategy, whereas those who did not receive remdesivir were assigned to the no remdesivir strategy. Main Outcomes and Measures: The primary outcome was all-cause graft loss (ACGL), a composite of graft failure and all-cause mortality. Secondary outcomes included all-cause mortality, cardiovascular events (CVEs), and long COVID. Per-protocol associations were estimated using a clone-censor-weight (CCW) approach with weighted Cox proportional hazards marginal structural regression models and robust SEs to calculate hazard ratios (HRs) and 95% CIs. Results: Among 432 KT recipients with symptomatic COVID-19 (median age, 57 years [IQR, 46-66 years]; 248 [57.4%] were male), 177 (41.0%) initiated early remdesivir and 255 (59.0%) received no remdesivir. Over 1 year of follow-up, early remdesivir initiation vs no remdesivir was associated with a lower risk of ACGL (HR, 0.53; 95% CI, 0.31-0.92) and CVEs (HR, 0.58; 95% CI, 0.35-0.98) after CCW adjustment. There was no significant association between early initiation of remdesivir and lower risk of all-cause mortality (HR, 0.51; 95% CI, 0.24-1.06) or long COVID (HR, 0.65; 95% CI, 0.21-2.05) in the weighted analysis. Conclusions and Relevance: In this target trial emulation, KT recipients with symptomatic acute COVID-19 who underwent early remdesivir treatment had reduced risk of ACGL and CVEs. These findings suggest that prompt initiation of remdesivir during COVID-19 illness may protect kidney allograft survival and cardiovascular health in this population.