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

Abstract 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.