Increased incidence of Graves' disease during the SARS‐CoV2 pandemic

Abstract

Introduction COVID‐19 has a wide spectrum of clinical severity and there is evidence that SARS‐Cov2 affects several organs and systems. Among the organs affected since the beginning of the pandemic, the relationship between SARS‐CoV‐2 infection and thyroid involvement has been demonstrated. Novel and highly effective messenger RNA and DNA‐based vaccines have been rapidly developed to decrease SARS‐CoV‐2 morbidity and mortality. Early after mass vaccinations, cases of thyroid dysfunction mainly including episodes of subacute thyroiditis, began to be reported like adverse effects. The objective of this study is to determine the impact of the pandemic, both due to SARS‐CoV2 infections and vaccinations, on the incidence of Graves' disease (GD). Methods Cross‐sectional, observational study comparing incidence of GD in adult population (over 18 years) before (2017–2019) and after (2020–2021) Covid‐19 pandemic. Only patients with new cases of GD, no relapsed diseases, were included. SARS‐CoV‐2 diagnosis was based on nucleic acid amplification tests on nasopharyngeal swabs or measurement of class M and class G antibodies to SARS‐CoV‐2 by highly specific assays. Data on incidence and vaccination related to SARS‐CoV‐2 infection were obtained from the public records from Castilla y León autonomous regional government. Results A total of 180 subjects were diagnosed and treated for GD during the study period. We observed a notable increase in expected GD cases in 2021 compared to 2017–19. The number of GD cases was higher in the second (Q2) quarter. Among 2021 GD cases, 42/66 patients (63.6%) had been vaccinated in the 90 days before symptom onset, but none of them in the first quarter of the year. A total of 97.7% were women with a mean age of 48.9 ( SD 15.6) years. On average they were diagnosed 19.9 ( SD 17.6) days after receiving the vaccine. A total of 7/42 (16.67%) had another previously diagnosed autoimmune disease and 11/42 (26.19%) were smokers. Discussion Our results show a notable increase in the incidence of GD during the year 2021, specially in women with a history of smoking. Hyper activation of the immune system induced by SARS‐CoV2 and by the recently released SARS‐COV‐2 vaccines has been highlighted in recent months. To assess whether this observed increase in the incidence of GD is sustained in the coming years or has simply been a precipitous trigger for individuals who were already predisposed to develop the disease, future studies will be needed.

Hyperthyroidism

“…During the SARS-CoV-2 (COVID-19) pandemic, cases of Graves disease and subacute thyroiditis related to COVID-19 infection or vaccination were reported, presumably due to the immunogenic nature of COVID-19 . A retrospective study reported a 2-fold increase in the incidence of Graves disease in a Spanish hospital in 2020-2021 compared with the pre–COVID-19 years (2017-2019) …”

“…[18][19][20] A retrospective study reported a 2-fold increase in the incidence of Graves disease in a Spanish hospital in 2020-2021 compared with the pre-COVID-19 years (2017-2019). 21…”

Graves’ Disease after mRNA COVID-19 Vaccination, with the Presence of Autoimmune Antibodies Even One Year Later

“…Under such circumstances, although the COVID-19 mRNA vaccine was developed and administered worldwide, various adverse effects have been reported, including cardiovascular diseases such as acute coronary syndrome (ACS) and myocarditis [ 2 , 3 , 4 ], and hyperthyroidism including Graves’ disease, Graves’ orbitopathy, subacute thyroiditis, and silent thyroiditis [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ].…”

“…Expected cases of Graves’ disease in 2021 increased markedly compared to 2017–2019. Two-thirds of patients had a history of vaccination in the 90 days prior to symptom onset [ 11 ]. In healthcare workers, a gradual increase in the mean thyroid-stimulating hormone (TSH) receptor antibody (TRAb) in response to frequent vaccination has been reported [ 14 ].…”

“…The main cause of Graves’ disease following COVID-19 vaccination is related to autoimmunity, which is explained by autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and cross-reactivity between thyroid tissue including thyroid peroxidase (TPO) and the SARS-COV2 spike protein [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. The mRNA vaccine contains adjuvants such as lipid nanoparticles (LNPs) that can trigger ASIA [ 16 , 17 ].…”