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.