Risk for thyroid eye disease rises within 4 weeks of COVID-19 vaccination
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Key takeaways:
- Adults who receive a COVID-19 vaccine have a 3.2 times higher risk for developing thyroid eye disease 28 days after vaccination.
- The risk for thyroid eye disease is higher for adults younger than 50 years.
Adults may have an increased risk for new-onset or recurrent thyroid eye disease in the 28 days after receiving a COVID-19 vaccine dose, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
“COVID-19 vaccines are associated with a 3.2-fold increased risk to develop thyroid eye disease, an autoimmune inflammation of orbital tissues, between 1 and 28 days following administration,” Ilaria Muller, MD, PhD, assistant professor in endocrinology and metabolism in the department of clinical sciences and community health at University of Milan, told Healio. “Such risk is highest in the first 14 days after vaccination and progressively decreases during the following weeks. The risk is even higher among people younger than 50 years of age, while it is not correlated with sex or other known risk factors for this disease.”
Muller and colleagues collected data from 98 consecutive adults with newly diagnosed or relapsing thyroid eye disease who attended a tertiary referral center for thyroid eye disease in Milan from 2021 to August 2022 (71 women; mean age, 50.8 years). The date of thyroid eye disease onset or reactivation was determined based on ocular signs or symptoms and the objective assessment of providers. Clinical history was collected for all adults. COVID-19 vaccine history, vaccination dates and the type of vaccine received were collected from a registry for all residents of the Lombardy region of Italy.
Of the study group, 83% received at least one COVID-19 vaccine dose. Participants received the second dose a median 34 days after the first dose, the third dose 223 days after the initial dose and the fourth dose a median 460 days after the first dose. Three vaccine doses were administered to 65% of adults. Of the participants, 6% had a COVID-19 infection before the study period and 23% had an infection during the study. New-onset thyroid eye disease occurred in 94% of participants and 93% had associated Graves’ disease. Thyroid dysfunction preceded thyroid eye disease for 70% of adults.
In an analysis that only included adults living in Lombardy, the risk for developing thyroid eye disease was increased 1 to 28 days after a COVID-19 vaccine dose compared with outside of that time frame (incidence rate ratio [IRR] = 3.27; 95% CI, 1.94-5.49).
“The risk of thyroid eye disease was highest in the first 14 days after vaccination and progressively decreased with time during the following weeks,” Muller said. “This further strengthens the link between COVID-19 vaccines and the development of thyroid eye disease.”
Adults younger than 50 years had a more than fourfold higher risk for developing thyroid eye disease in the 28 days after a vaccine dose than during any other period (IRR = 4.7; 95% CI, 2.39-9.23). Among adults aged at least 50 years, the risk for developing thyroid eye disease in the 28 days after vaccination was 2.31 times higher compared with outside that time frame (IRR = 2.31; 95% CI, 1.16-4.58).
“We suggest monitoring of young people, and those at risk for autoimmunity, undergoing COVID-19 vaccination,” Muller said. “A balanced and personalized harm-benefit analysis of COVID-19 vaccination should also be encouraged in these people, as well as those already affected with thyroid autoimmunity.”
Muller said case-control studies and research analyzing the mechanisms behind the association between COVID-19 vaccines and thyroid eye disease must be conducted. Additionally, she said active surveillance is needed to assess thyroid eye disease diagnoses after COVID-19 vaccination in real time.
For more information:
Ilaria Muller, MD, PhD, can be reached at ilaria.muller@unimi.
Perspective
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This study ascertained the development of thyroid eye disease after COVID-19 vaccination. It found that there was an increased risk of developing thyroid eye disease shortly after COVID vaccination, with most cases presenting as new cases. There were 98 patients included, 92 had new thyroid eye disease, six had re-activation of thyroid eye disease. There was a three-fold increase of thyroid eye disease 4 weeks post-vaccination, with the risk not vaccine dose quantity dependent. There was no evidence of modification by sex, cigarette smoking, radioactive iodine treatment or vaccine type.
The study used a self-controlled case series study, case-only analysis, with active thyroid eye disease defined as a clinical activity score of more than 3 out of 7 at the first exam, and more than 4 out of 10 in subsequent exams.
The main limitation of the study included a small sample size (98 patients) that were from a highly selected population from one tertiary referral center for thyroid eye disease in Italy. Risk of thyroid eye disease according to different vaccine types could not be drawn. It is important to note that the history of SARS-CoV-2 natural infection did not influence the occurrence of thyroid eye disease
The findings showed that the risk of thyroid eye disease is increased after COVID-19 vaccination, independent of the number of administered COVID doses. The risk is worse after 14 days and in people younger than 50 years. To determine the magnitude of thyroid eye disease risk, a case control or larger cohort study should be done. However, this study is important because it shows that more active surveillance and longitudinal studies during future vaccinations need to be done. There also need to be further studies to better elucidate the proposed mechanisms of action, which include spike protein interactions with the ACE-2 receptor, cross-reactivity with thyroid self-proteins, immune reactions induced by adjuvants and gut microbia alterations during vaccination.
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