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Graves’ disease after mRNA COVID-19 vaccination, with the persistence of autoantibodies one year after the vaccination

The Japanese scientists presented a case report of a new-onset Graves’ disease that developed after the messenger RNA (mRNA) COVID-19 vaccination, with the persistence of autoantibodies to the thyroid-stimulating hormone receptor (anti-TSHR-Abs) one year after the vaccination.

In both vaccines (mRNA-1273 and BNT162b2), the mRNA sequence determines the structure and assembly of the immunogen, the SARS-CoV-2 spike (S) glycoprotein. After the mRNA COVID-19 vaccination, various adverse effects have been reported, including Graves’ disease, Graves’ orbitopathy, subacute thyroiditis, and silent thyroiditis. Graves’ disease is a disorder caused by anti-TSHR-Abs. Unlike most autoantibodies, which are inhibitory, anti-TSHR-Abs stimulate the synthesis and secretion of thyroid hormones.

 

Case description

 

A 45-year-old man was admitted to the emergency department with chest discomfort and suspected myocarditis following vaccination. He had received the second mRNA COVID-19 vaccine (Moderna) one week before the onset of symptoms. There were no signs of myocarditis, and the electrocardiogram showed a sinus tachycardia of 116 beats per minute without changes in the ST–T segment. A blood examination and the transthoracic echocardiogram showed no evidence of myocarditis. He did not have a family history of autoimmune diseases, including thyroid disease. Two years earlier, blood tests showed normal thyroid function. 

Two weeks after a discharge, he returned to the hospital complaining of palpitations, hand tremors, and weight loss. He was diagnosed with Graves’ disease based on high levels of free triiodothyronine (FT3) (27.5 pg/mL), free thyroxine (FT4) (6.42 ng/dL), and anti-TSHR-Abs (17.5 IU/L), and low concentrations of thyroid-stimulating hormone (TSH) (<0.01 mIU/L). A thyroid ultrasound showed diffuse swelling of the thyroid gland and an internal hypoechoic image suggestive of a diffuse goiter consistent with Graves’ disease.

The patient was treated with thiamazole. FT4 levels, heart rate, and other symptoms normalized after 30 days. However, four months after the treatment, the concentration of anti-TSHR-Ab increased from 17.5 to 30.9 IU/L. One year after the vaccination, the dosages of thiamazole and bisoprolol were reduced, the FT4 level remained stable, and the anti-TSHR-Ab concentration fell to 6.3 IU/L, but it did not become negative.

The authors discussed the possible causes of autoimmunity in Graves’ disease that developed after mRNA COVID-19 vaccination. They emphasized that mRNA vaccines contain adjuvants that increase the concentrations of inflammatory cytokines such as interleukin (IL) -1 and IL-6. These cytokines can trigger an adjuvant-induced autoimmune/inflammatory syndrome. In addition, thyroid tissue expresses angiotensin-converting enzyme 2 (ACE2) receptors. The SARS-CoV-2 S protein, produced by the mRNA vaccine, binds to ACE2, leading to the down-regulation of ACE2 and a release of IL-1 and IL-6.

There is also a theory of cross-reactivity, according to which the thyroid peroxidase and the SARS-CoV-2 S protein have a homology of amino acid sequences (molecular mimicry). The cross-reactivity between the S protein produced by the mRNA vaccine and the thyroid tissue could trigger the production of autoantibodies against the thyroid antigens. 

The authors recommended that in cases of chest symptoms after COVID-19 vaccination possible thyroid disease should be ruled out by determining the plasma levels of FT4, TSH, and troponin. Even though Graves’ disease is more prevalent among women, post-vaccination cases of Graves’ disease have been reported in males without a history of autoimmune diseases, as in this study, and, therefore, caution is advised.

 

This article was published in Vaccines.

Journal Reference

Nakamura, F, et al. Graves’ Disease after mRNA COVID-19 Vaccination, with the Presence of Autoimmune Antibodies Even One Year Later. Vaccines 2023, 11, 934. (Open Access)  https://doi.org/10.3390/vaccines11050934

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