Background: Vaccination is a widely adopted measure against the severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) causing Covid-19 pandemic. Both SARS-CoV-2 infection and Covid-19 vaccines have been associated with several thyroid disorders. We studied the risk of Graves orbitopathy (GO) following Covid-19 vaccination.
Methods: The study included 98 consecutive patients (71 females and 27 males, mean-age 50 years) attending our tertiary referral centre for new-onset (n=90) or reactivation (n=8) of GO occurred in the period Jan 2021 Aug 2022, immediately following the extensive Covid-19 vaccination campaign launched in late 2020. GO was associated to Graves disease in 91 (93%), euthyroidism in 5 (5%) and Hashimotos thyroiditis in 2 (2%) patients. Family history for thyroid/autoimmune disorders was positive in 54 (55%) patients. We used a self-controlled-case-series study design, validated in assessing vaccine safety. For each vaccinated patient, we calculated person-days in time-windows after each dose, defined as exposed if GO onset/reactivation occurred 1-30 days after vaccination and unexposed if occurring outside such time-window. Poisson regression models were fitted to calculate incidence rate ratio (IRR) and 95% confidence-intervals (CI) of exposed vs unexposed. Sensitivity analyses were conducted considering only new-onset GO, gender, age, smoking, Covid-19 vaccine type and number of doses.
Results: Covid-19 vaccines were administered in 81 (83%) and never in 13 (13%) patients; data were missing in 4 patients. Of the 81 vaccinated subjects, 25 (31%) developed GO 1-30 days after vaccination (exposed) and 56 (69%) outside such time-window (unexposed). The overall IRR for GO was 3.12 (CI 1.94-5.02) and as high as 5.10 (CI 2.61-9.93) in patients below 50 years of age. Gender, smoking, Covid-19 vaccine type and number of doses did not significantly impact on the overall IRR, also when restricting the analysis to cases of new disease onset only. The GO severity was similar across the study subgroups. SARS-CoV-2 infection occurred in 23/98 (23%) patients during the study period and seemed not associated with GO.
Conclusions: This study shows a 3-fold increased risk of either developing or reactivating GO shortly after Covid-19 vaccination, rising-up to 5-fold in subjects of less than 50 years of age. Possible mechanisms involve the interaction of the spike protein with the widely expressed ACE-II receptor, cross-reactivity of the spike with thyroid self-proteins or immune reactions induced by adjuvants. Until more safety data about Covid-19 vaccines will be available, caution and strict monitoring of individuals undergoing vaccination is suggested, especially if young and prone to develop thyroid autoimmunity.
13 May 2023 - 16 May 2023