Background: Invasive fungal infections (IFI) are a serious complication in kidney transplant recipients (KTR), leading to increased mortality and allograft failure. Common respiratory viral infections, such as COVID-19, are associated with IFIs, which might compound adverse transplant outcomes.

Methods: This retrospective cohort study examined adult KTRs transplanted at Johns Hopkins from 2012 to 2018 with follow up through 2023. The association of COVID-19 hospitalization and IFI exposure with all-cause graft loss (ACGL) was assessed using a stochastic extension stratification method followed by Cox regression.

Results: Of 1453 KTRs, 440 experienced at least one COVID-19-associated hospitalization. COVID-19 hospitalization was associated with a 2.54-times greater risk of ACGL (95% CI, 1.78–4.31, p < 0.001) compared to matched KTRs without COVID-19-associated hospitalization. Of 16 KTRs with COVID-19- and IFI-associated hospitalizations, the risk of ACGL was 6.47-times higher (95% CI 1.53–27.26, p = 0.010) as compared to matched KTRs with COVID-19-associated hospitalization, alone. COVID-19-associated hospitalization increased risk of ACGL, which was further elevated in those with a history of IFI.

Conclusions: These results highlight the continued need for preventative measures, particularly targeted against SARS-CoV2, to improve transplant outcomes in this high-risk population.