Thyroid Inflammation and Immunity During the COVID-19 Pandemic: A Comprehensive Review and Case Study

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the development of various vaccines. Reports have emerged suggesting a possible association between SARS-CoV-2 vaccination and the onset of thyroid diseases. This review explores the clinical aspects of thyroid disorders following SARS-CoV-2 vaccination, including a case report of a patient with concomitant subacute thyroiditis (SAT) and Graves’ disease (GD) with blocking thyrotropin receptor autoantibodies (TSH-R-Ab) following SARS-CoV-2 vaccination. SAT, characterized by transient inflammation of the thyroid gland, has been reported after SARS-CoV-2 vaccination. GD, an autoimmune hyperthyroidism, has also been observed post-vaccination, often with stimulating TSH-R-Ab. Graves’ orbitopathy (GO) has been associated with SARS-CoV-2 vaccination in patients with a history of immune thyroid disease. The unique case underscores a very rare thyroid condition of functional hypothyroidism in possible relation to SARS-CoV-2 vaccination and the usefulness of functional analysis of TSH-R-Ab that can provide valuable insights into disease pathogenesis and help to guide treatment. This review highlights the need for continued monitoring and awareness of potential thyroid-related complications following SARS-CoV-2 vaccination.

Key words

COVID-19 - SARS-CoV-2 vaccination - subacute thyroiditis - Graves’ disease - thyrotropin receptor autoantibodies

Publication History

Received: 23 May 2023

Accepted after revision: 04 December 2023

Accepted Manuscript online:
04 December 2023

Article published online:
29 January 2024

• References

• 1 Zhou P, Yang XL, Wang XG. et al. Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 588: E6
• 2 Chung YH, Beiss V, Fiering SN. et al. COVID-19 Vaccine frontrunners and their nanotechnology design. ACS Nano 2020; 14: 12522-12537
• 3 Ippolito S, Gallo D, Rossini A. et al. SARS-CoV-2 vaccine-associated subacute thyroiditis: insights from a systematic review. J Endocrinol Invest 2022; 45: 1189-1200
• 4 Jafarzadeh A, Nemati M, Jafarzadeh S. et al. Thyroid dysfunction following vaccination with COVID-19 vaccines: a basic review of the preliminary evidence. J Endocrinol Invest 2022; 45: 1835-1863
• 5 Nishihara E, Ohye H, Amino N. et al. Clinical characteristics of 852 patients with subacute thyroiditis before treatment. Intern Med 2008; 47: 725-729
• 6 Yorulmaz G, Sahin Tekin M. SARS-CoV-2 vaccine-associated subacute thyroiditis. J Endocrinol Invest 2022; 45: 1341-1347
• 7 Oguz SH, Sendur SN, Iremli BG. et al. SARS-CoV-2 Vaccine-induced thyroiditis: safety of revaccinations and clinical follow-up. J Clin Endocrinol Metab 2022; 107: e1823-e1834
• 8 Iremli BG, Sendur SN, Unluturk U. Three cases of subacute thyroiditis following SARS-CoV-2 vaccine: postvaccination ASIA syndrome. J Clin Endocrinol Metab 2021; 106: 2600-2605
• 9 Chee YJ, Liew H, Hoi WH. et al. SARS-CoV-2 mRNA Vaccination and Graves' disease: a report of 12 cases and review of the literature. J Clin Endocrinol Metab 2022; 107: e2324-e2330
• 10 Brancatella A, Viola N, Santini F. et al. COVID-induced thyroid autoimmunity. Best Pract Res Clin Endocrinol Metab 2023; 101742
• 11 Bostan H, Ucan B, Kizilgul M. et al. Relapsed and newly diagnosed Graves' disease due to immunization against COVID-19: a case series and review of the literature. J Autoimmun 2022; 128: 102809
• 12 Patrizio A, Ferrari SM, Elia G. et al. Graves' disease following SARS-CoV-2 vaccination: a systematic review. Vaccines (Basel) 2022; 10: 1445
• 13 di Filippo L, Castellino L, Allora A. et al. Distinct clinical features of post-COVID-19 vaccination early-onset Graves' disease. J Clin Endocrinol Metab 2022; 108: 107-113
• 14 Eckstein AK, Losch C, Glowacka D. et al. Euthyroid and primarily hypothyroid patients develop milder and significantly more asymmetrical Graves ophthalmopathy. Br J Ophthalmol 2009; 93: 1052-1056
• 15 Chin YH, Ng CH, Lee MH. et al. Prevalence of thyroid eye disease in Graves' disease: A meta-analysis and systematic review. Clin Endocrinol (Oxf) 2020; 93: 363-374
• 16 Abeillon-du Payrat J, Grunenwald S, Gall E. et al. Graves' orbitopathy post-SARS-CoV-2 vaccines: report on six patients. J Endocrinol Invest 2023; 46: 617-627
• 17 Mohamed A, Tzoulis P, Kossler AL. et al. New onset or deterioration of thyroid eye disease after mRNA SARS-CoV-2 vaccines: report of 2 cases and literature review. J Clin Endocrinol Metab 2023; 108: 979-985
• 18 Patrizio A, Ferrari SM, Antonelli A. et al. Worsening of Graves' ophthalmopathy after SARS-CoV-2 mRNA vaccination. Autoimmun Rev 2022; 21: 103096
• 19 Patrizio A, Ferrari SM, Antonelli A. et al. A case of Graves' disease and type 1 diabetes mellitus following SARS-CoV-2 vaccination. J Autoimmun 2021; 125: 102738
• 20 Kahaly GJ, Bartalena L, Hegedus L. et al. 2018 European thyroid association guideline for the management of Graves' hyperthyroidism. Eur Thyroid J 2018; 7: 167-186
• 21 Kahaly GJ, Diana T, Kanitz M. et al. Prospective trial of functional thyrotropin receptor antibodies in Graves disease. J Clin Endocrinol Metab 2020; 105: e1006-e1014
• 22 Kahaly GJ, Frommer L, Schuppan D. Celiac disease and endocrine autoimmunity - the genetic link. Autoimmun Rev 2018; 17: 1169-1175
• 23 Muller I, Cannavaro D, Dazzi D. et al. SARS-CoV-2-related atypical thyroiditis. Lancet Diabetes Endocrinol 2020; 8: 739-741
• 24 Desailloud R, Hober D. Viruses and thyroiditis: an update. Virol J 2009; 6: 5
• 25 Shoenfeld Y, Agmon-Levin N. 'ASIA' - autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun 2011; 36: 4-8
• 26 Werner SC. Graves' disease following acute (subacute) thyroiditis. Arch Intern Med 1979; 139: 1313-1315
• 27 Nagai Y, Toya T, Fukuoka K. et al. Occurrence and spontaneous remission of Graves' hyperthyroidism preceded by painless thyroiditis. Endocr J 1997; 44: 881-885
• 28 Jafarzadeh A, Nemati M, Jafarzadeh S. et al. Thyroid dysfunction following vaccination with COVID-19 vaccines: a basic review of the preliminary evidence. J Endocrinol Invest 2022; 45: 1835-1863
• 29 Fatourechi V, Aniszewski JP, Fatourechi GZ. et al. Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study. J Clin Endocrinol Metab 2003; 88: 2100-2105
• 30 Kahaly GJ, Diana T, Olivo PD. Tsh Receptor antibodies: relevance & utility. Endocr Pract 2020; 26: 97-106
• 31 Diana T, Wuster C, Olivo PD. et al. Performance and specificity of 6 immunoassays for TSH receptor antibodies: a multicenter study. Eur Thyroid J 2017; 6: 243-249
• 32 Faust B, Billesbolle CB, Suomivuori CM. et al. Autoantibody mimicry of hormone action at the thyrotropin receptor. Nature 2022; 609: 846-853
• 33 Duan J, Xu P, Luan X. et al. Hormone- and antibody-mediated activation of the thyrotropin receptor. Nature 2022; 609: 854-859
• 34 Diana T, Olivo PD, Kahaly GJ. Thyrotropin receptor blocking antibodies. Horm Metab Res 2018; 50: 853-862
• 35 Evans M, Sanders J, Tagami T. et al. Monoclonal autoantibodies to the TSH receptor, one with stimulating activity and one with blocking activity, obtained from the same blood sample. Clin Endocrinol (Oxf) 2010; 73: 404-412
• 36 Takasu N, Yamashiro K, Ochi Y. et al. TSBAb (TSH-stimulation blocking antibody) and TSAb (thyroid stimulating antibody) in TSBAb-positive patients with hypothyroidism and Graves' patients with hyperthyroidism. Horm Metab Res 2001; 33: 232-237
• 37 McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid 2013; 23: 14-24
• 38 Takasu N, Matsushita M. Changes of TSH-stimulation blocking antibody (TSBAb) and thyroid stimulating antibody (TSAb) over 10 years in 34 TSBAb-positive patients with hypothyroidism and in 98 TSAb-positive Graves' patients with hyperthyroidism: reevaluation of TSBAb and TSAb in TSH-receptor-antibody (TRAb)-positive patients. J Thyroid Res 2012; 182176