Study: Some Organ Recipients Rejecting Transplant After Covid Vaccine

According to a new study published in the Journal of Clinical Medicine, acute corneal allografts are being rejected by immunized patients who've undergone the procedure. Researchers say the underlying cause could be tied to a systemic inflammatory response elicited by the shot post-jab.

The cornea is the outermost layer of a person’s eye. Corneal grafts are used to restore a damaged cornea. The surgery is known to be one of the most successful organ transplant procedures with low rejection rates. It restores vision, reduces eye pain and improves the appearance of the diseased cornea.

Japanese researchers compiled data from 23 studies. A total of 23 eyes from 21 patients who had undergone corneal graft procedures were assessed. Graft rejection occurred anywhere from one day to six weeks after vaccination in all patients–some who underwent the procedure as far back as twenty years ago.

Since the beginning of the COVID-19 pandemic in 2019, efforts toward vaccination have continued worldwide due to the uncontrollable spread of SARS-CoV-2 infection and the increasing number of COVID-19 cases. However, despite the low occurrence rates of high-risk complications after vaccination, an appreciable number of vaccine recipients have experienced a wide range of post-vaccination symptoms. At present, COVID-19 vaccines are believed to be associated with a spectrum of systemic symptoms, and appropriate interventions should be undertaken on a case-by-case basis. In this systematic review, we extracted data regarding clinical features of acute corneal allograft rejection (21 patients [23 eyes]) that occurred after the administration of the COVID-19 vaccine. Among them, >95% of eyes (22/23 eyes) had corneal allograft rejection within 3 weeks from vaccination (mean: 10.4 days, median: 7 days). As the global society promotes additional booster schedules in consideration of emerging variants, it is empirical that the effects of these vaccines on corneal grafts be elucidated. To establish appropriate immune-modulatory interventions, continued data accrual and investigation of the effects of COVID-19 vaccines should be conducted by observing the vaccination course and associated physiological changes in corneal allograft recipients.

In our analysis of 21 patients (23 eyes) with signs of corneal allograft rejection after receiving COVID-19 vaccines, the median interval between corneal transplantation and graft rejection after COVID-19 vaccination was 2 years. Two of these patients (two eyes) underwent PKP > 20 years ago and had no history of acute or chronic corneal allograft rejection [33,38]. [Note: PKP is short for penetrating keratoplasty, a.k.a. a corneal transplant] The long-term stability and temporariness of vaccination and allograft rejection suggest that immune responses to the vaccine may have played a role in transplant rejection. Two separate studies investigated the possibility of confounding viral infections, including herpes simplex and varicella-zoster viral infections, which are known risk factors for corneal allograft rejection after PKP or DMEK [20,38], through anterior-chamber, aqueous-humor polymerase chain reaction (PCR). However, PCR results for confounding viral infections were negative in both patients. Additionally, two cases (four eyes) of post-DMEK and -DSAEK bilateral corneal allograft rejection after vaccination were reported. These cases suggest a systemic inflammatory etiology for corneal graft rejection [33,38]. The detailed pathophysiology of the relationship between COVID-19 vaccination and corneal allograft rejection remains unclear. However, the present study revealed cases with minimal confounding variables and appreciable temporal correlation with COVID-19 vaccination, positing the vaccine’s role in inducing acute corneal allograft rejection.

Corneal transplantation is associated with low rates of allograft rejection, probably due to ocular immune privilege [52,53,54]. This underscores the importance of recognizing the possibility of COVID-19 vaccine-led corneal allograft rejection in the 21 patients (23 eyes) included in the present study [20,29,30,31,32,33,34,35,36,37,38,39,40]. The interval between administration of the COVID-19 vaccine and corneal graft rejection ranged from 1 day to 6 weeks (mean: 10.4 days; median: 7 days [20,29,30,31,32,33,34,35,36,37,38,39,40].) The concerns regarding vaccine-associated acute allograft rejection extend beyond the COVID-19 vaccines, especially those related to influenza, hepatitis B, tetanus, and yellow fever viral vaccines [21,55,56]. The incidence rate of vaccine-associated corneal graft rejection is certainly modest in terms of corneal transplant frequency. However, the projected societal shift towards a more frequent vaccination schedule calls for clinicians to be cognizant of a possible connection between the temporality of vaccine administration and graft rejections. Cell-mediated immune responses were confirmed in previous studies for the vaccine types included in this systematic review, including BNT162b2 (Pfizer), mRNA-1273 (Moderna), ChAdOx1 (AstraZeneca), and CoronaVac (Sinovac) vaccines [57,58,59,60,61,62]. Regardless of the vaccine type, vaccination significantly increased anti-spike-neutralizing antibodies, antigen-specific CD4+ T-cell responses, and inflammatory cytokines, including interferon (IFN)-γ and interleukin-2 [57,58,59,60,61,62]. IFN-γ plays a central role in the acute rejection process [63], and the resultant T helper type 1–dominant immune response may have evoked corneal allograft rejection in the vaccinated individuals [63]. [Sources and citations are all linked in the study]

"One hundred thirty-six cases from fifty-two articles were included in the qualitative synthesis of this systematic review (56 solid organs rejected post-SARS-CoV-2 vaccination and 40 solid organs rejected following COVID-19 infection). Cornea rejection (44 cases) was the most frequent organ observed post-SARS-CoV-2 vaccination and following COVID-19 infection, followed by kidney rejection (36 cases), liver rejection (12 cases), lung rejection (2 cases), heart rejection (1 case) and pancreas rejection (1 case). [...] A total of fifty-six solid organ rejections were reported post-SARS-CoV-2 vaccination [Pfizer-BioNTech (n = 31), Moderna (n = 14), Oxford Uni-AstraZeneca (n = 10) and Sinovac-CoronaVac (n = 1)]."