Increased risk of corneal transplant rejection following SARS-CoV-2 infection and vaccination.

BACKGROUND: To determine the impact of COVID-19 infection and vaccination on risk of corneal transplant rejection. METHODS: All corneal transplants performed in Auckland, New Zealand (NZ), between January 2010 and December 2022 were included. Demographic, clinical, and surgical characteristics were recorded, along with COVID-19 vaccination and infection history. Time to corneal transplant rejection was analysed using Weibull survival regression with clustered standard errors at the graft level to account for repeated events and time-varying covariates. RESULTS: A total of 1183 corneal transplants were performed in 926 patients, with a median age of 52 years (IQR 32-70); 47.5% were female. The median follow-up was 11.7 years ± 3.8. Within 3 months following COVID-19 vaccination, 1.1% of corneal transplants were rejected; within the same period following COVID-19 infection, 2.3% of transplants rejected. Overall, 277 transplants (23.4%) experienced rejection. On multivariable analysis, COVID-19 vaccination within 3 months was associated with elevated rejection risk (HR 1.834, p = 0.012), while COVID-19 infection within 3 months carried the greatest risk (HR 3.533, p < 0.001). Corneal transplant rejection was associated with significantly worse visual acuity follow-up (rejection median 20/160, no rejection 20/70, p < 0.001). CONCLUSIONS: COVID-19 vaccination and infection were independently associated with an increased likelihood of corneal transplant rejection, with infection conferring the greatest risk. These findings suggest that systemic immune activation induced by SARS-CoV-2 immunisation may disrupt the delicate balance of transplant immunity and tolerance. This is the first large cohort study demonstrating an independent association between recent COVID-19 infection, vaccination, and increased risk of corneal graft rejection.