Increased Risk of Thyroid Eye Disease Following Covid-19 Vaccination

Abstract

Context SARS-CoV-2 infection and Covid-19 vaccines have been associated with thyroid disorders. Objective We analyzed the risk of Thyroid Eye Disease (TED) following Covid-19 vaccination. Design Self-controlled case series study. Setting Tertiary referral center for TED. Participants A total of 98 consecutive patients with newly-developed (N = 92) or reactivated (N = 6) TED occurring between January 1, 2021, and August 31, 2022. Intervention Assessment of TED in patients undergoing Covid-19 vaccination. Main Outcome Measures Person-days were defined as exposed if TED occurred 1-28 days after vaccination, and unexposed if occurring outside such time-window. Conditional Poisson regression models were fitted to calculate incidence-rate-ratio (IRR), and 95% confidence-intervals (95%CI) of exposed vs unexposed. Sensitivity analyses were conducted considering different exposed periods and effect modification by potential TED risk factors. Results Covid-19 vaccines were administered in 81 subjects, 25 (31%) of whom developed TED in exposed, and 56 (69%) in unexposed periods. The IRR for TED was 3.24 (95%CI 2.01-5.20), and 4.70 (95%CI 2.39-9.23) in patients below 50 years of age. Sex, smoking, and radioiodine treatment did not modify the association between TED and vaccination. TED risk was unrelated to the number of vaccine doses, and progressively decreased over time following vaccination (P-trend = 0.03). Conclusions The risk of TED was significantly increased after Covid-19 vaccination, especially in subjects below 50 years of age. Possible mechanisms include spike protein interaction with ACE-II receptor, cross-reactivity with thyroid self-proteins, and immune reactions induced by adjuvants. We suggest monitoring of individuals undergoing Covid-19 vaccination, especially if young and at risk for autoimmunity.

Importance of Examining Incidentality in Vaccine Safety Assessment

“…These have been performed using a single statistical method in many papers. The PubMed search results were as follows: the cohort study, 276 [3,[23][24][25][26][27][28]; the SCCS, 59 [29][30][31][32][33]; and the SCRI, 3 [21,34,35]. Four papers [16,[36][37][38] using the cohort study and the SCCS, and three papers [39][40][41] using the cohort study and the SCRI have been published.…”

“…Thus, further studies should be conducted using these two methods. Papers with graphs illustrating the number of days from COVID-19 vaccination to a particular adverse event and case count were limited (11.6%; 8/69: the SCCS, 5 [29][30][31][32][33]; and the SCRI, 3 [21,35,41]). When graphs are not presented, evaluating whether the risk period setting is appropriate is impossible.…”

Immune checkpoints: new insights into the pathogenesis of thyroid eye disease

“…The fundamental pathological process in the initial stages of TED involves the loss of T cell tolerance to the thyroid-stimulating hormone (TSH, or thyrotropin) receptor (TSHR), which occurs due to multiple factors ( 24 ). Of note, Covid-19 vaccination appears to increase the risk of TED development ( 25 ). After the loss of immune tolerance, B cells are activated through their interaction with helper T cells (Th), resulting in the production of autoantibodies.…”