Discussion
Episcleritis has been previously found in a patient confirmed with COVID-19 infection (8, 9). In this report, we presented a case of scleritis after the third dose of COVID-19 vaccination with inactivated Sinopharm vaccine. Recently, Pichi and colleagues reported four cases scleritis and episcleritis following the first dose of COVID-19 Sinopharm vaccination (10). There has been few reports of mild scleritis or episcleritis caused by live virus vaccination previously (11).
Regarding various reports of ocular adverse events induced after vaccination, COVID-19 vaccination-associated scleritis would not be exempt in surprising. The pathogenesis and mechanism of this immune response, remains the question. The most frequently proposed mechanism include molecular mimicry between scleral and vaccine peptides as well as hypersensitivity due to antigen-specific cell and antibody reactions (12). Moreover, although safe in most of the population, vaccine adjuvants that were added to achieve the desired protection, led to autoinflammatory syndromes particularly connective tissue disorders due to different nucleic acid metabolism (9, 13, 14). Noteworthy, inactivated COVID-19 vaccines stimulate T helper 2 cell reactions causing an increase in inflammatory (15). The addition of alum as an adjuvant aggravated immunopathologic reactions (16).
The genes for immunity, inflammation, and coagulation are part of X chromosome, so we may suspect that viral interactions associated with human genes could induce an abnormal immune response in COVID-19. Besides, according to Manzo et al., the presence of excess antigen and the formation of relatively resistant soluble antigen-antibody immune complexes after exposure to SARS-CoV-2 may cause persistent inflammation in organs (17). There are several reported cases of ocular inflammation and related conditions following COVID-19 vaccination. These include anterior uveitis (7, 18), scleritis (7), episcleritis (7), multiple evanescent white dot syndrome, Vogt-Koyanagi-Harada disease (19), panuveitis (20), choroiditis (21), and central serous chorioretinopathy (22). Most cases were successfully treated with corticosteroid therapy, including topical, intravitreal, and/or systemic administration, and many patients achieved complete recovery of their baseline visual acuity. A case series of orbital inflammation following mRNA vaccines was also described, with all cases successfully treated with oral prednisolone (23). It is important for healthcare providers to be aware of these potential ocular reactions to COVID-19 vaccination and to monitor patients closely for any signs or symptoms of ocular inflammation or related conditions.
As mentioned, our patient didn’t show any serious reaction to previous doses of inoculation until the first booster. These reactions were found to be induced by activation of the secondary immune response; the memory cells (24). Comparing to the first and second doses of vaccinations, Rahmani et al. Reported that booster doses are more probable to stimulate rare AEs including neurological symptoms (25). Moreover, authors suggested hormonal, genetic, and behavioural factors along with the time between the primary cycle to the first booster dose. The more the time between the booster dose and the first administration, the higher the immunogenic effect after the third shot (25). Consequently, further studies could elucidate the proper time of the booster inoculations, particularly for high-risk patients in order to prevent serious reactions.
Vaccine-associated maladaptive immune response becomes more important in patients with autoimmune diseases. A study demonstrated that ocular inflammatory AEs following vaccination could be the first presentation of an undiagnosed autoimmune disease (26). Thus, there should be further assessments in patients presenting with ophthalmologic inflammatory reactions following COVID-19 vaccination.