The long-term impact of SARS-CoV-2 infection on kidney allograft survival remains incompletely understood, particularly regarding the influence of vaccination, acute kidney injury (AKI), and post-infection immunosuppression. We conducted a retrospective analysis of 129 kidney transplant recipients with confirmed SARS-CoV-2 infection between March 2020 and March 2022 with a median follow-up of 50 months. Among 129 recipients, 106 (82%) received vaccination at any time before or after SARS-CoV-2 infection (82%) while 23 (18%) remained unvaccinated. Unvaccinated patients experienced significantly lower long-term graft survival (52% vs. 85%; p = 0.0004) and patient survival (83% vs. 99%; p = 0.0003) compared with vaccinated recipients. AKI occurred in 15% of recipients and independently predicted graft failure (aHR 2.88; p = 0.0341). Post–SARS-CoV-2 serum creatinine and albuminuria were strong prognostic markers of graft loss. Unvaccinated status independently predicted graft failure in both transplantation-anchored (aHR 2.80; p = 0.0342) and SARS-CoV-2–anchored models (aHR 5.31; p = 0.0004). Continuation of mycophenolate mofetil at post-infection assessment was associated with reduced graft-failure risk (aHR 0.99; p = 0.0193). These findings underscore the importance of sustained vaccination in preserving long-term allograft function.

DMD holds patent US-2020-0048713-A1 titled Methods of Detecting Cell-Free DNA in Biological Samples licensed to Eurofins Viracor and receives royalties from UpToDate. DMD participated in industry sponsored studies sponsored by AlloVir Inc., CSL Behring, Travere Therapeutics, and Memo Therapeutics AG and serves as a consultant for CareDx and Memo Therapeutics. DMD also serves on the Board of Directors for American Society of Transplantation.

Funding: ID was The EU NextGenerationEU funded this study through the Recovery and Resilience Plan for Slovakia under project number 09I03-03-V04-00211.This work was supported, in part, by an award from NIH to MS (NIH MERIT Award, R337AI051652).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of The Weill Cornell Medicine gave ethical approval for this work

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Anonymized data that support the findings of this study are available from the corresponding author upon reasonable request, subject to approval by the local ethics committee and data protection regulations.