Endocrinol Metab.  2021 Jun;36(3):582-589. 10.3803/EnM.2021.983.

Insights from a Prospective Follow-up of Thyroid Function and Autoimmunity among COVID-19 Survivors

• Lui DTW
• Lee CH
• Chow WS
• Lee ACH
• Tam AR
• Fong CHY
• Law CY
• Leung EKH
• To KKW
• Tan KCB
• Woo YC
• Lam CW
• Hung IFN
• Lam KSL

• KMID: 2517648
• DOI: http://doi.org/10.3803/EnM.2021.983

Abstract

Background
The occurrence of Graves’ disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors.
Methods
We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months.
Results
In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer.
Conclusion
Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

Keyword

COVID-19; SARS-CoV-2; Thyroid function tests; Thyroiditis; Euthyroid sick syndromes; Thyroid gland

Figure

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  Fig. 1 Changes in thyroid function status in all 122 patients included. fT3, free triiodothyronine; fT4, free thyroxine; TSH, thyroid-stimulating hormone.

Reference

1. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020; 324:782–93.

2. Pal R, Banerjee M. COVID-19 and the endocrine system: exploring the unexplored. J Endocrinol Invest. 2020; 43:1027–31.

3. Brancatella A, Ricci D, Viola N, Sgro D, Santini F, Latrofa F. Subacute thyroiditis after SARS-COV-2 infection. J Clin Endocrinol Metab. 2020; 105:dgaa276.

4. Scappaticcio L, Pitoia F, Esposito K, Piccardo A, Trimboli P. Impact of COVID-19 on the thyroid gland: an update. Rev Endocr Metab Disord. 2020; 25:1–13.

5. Brancatella A, Ricci D, Cappellani D, Viola N, Sgro D, Santini F, et al. Is subacute thyroiditis an underestimated manifestation of SARS-CoV-2 infection?: insights from a case series. J Clin Endocrinol Metab. 2020; 105:dgaa537.

6. Tee LY, Harjanto S, Rosario BH. COVID-19 complicated by Hashimoto’s thyroiditis. Singapore Med J. 2020. Jul. 16. [Epub]. https://doi.org/10.11622/smedj.2020106 .

7. Mateu-Salat M, Urgell E, Chico A. SARS-COV-2 as a trigger for autoimmune disease: report of two cases of Graves’ disease after COVID-19. J Endocrinol Invest. 2020; 43:1527–8.

8. Nakano Y, Kurihara H, Sasaki J. Graves’ disease following subacute thyroiditis. Tohoku J Exp Med. 2011; 225:301–9.

9. Papi G, Ezzat S. Progression of subacute (de Quervain’s) thyroiditis into Hashimoto’s thyroiditis. Thyroid. 2004; 14:477–8.

10. Chen M, Zhou W, Xu W. Thyroid function analysis in 50 patients with COVID-19: a retrospective study. Thyroid. 2021; 31:8–11.

11. Muller I, Cannavaro D, Dazzi D, Covelli D, Mantovani G, Muscatello A, et al. SARS-CoV-2-related atypical thyroiditis. Lancet Diabetes Endocrinol. 2020; 8:739–41.

12. Khoo B, Tan T, Clarke SA, Mills EG, Patel B, Modi M, et al. Thyroid function before, during, and after COVID-19. J Clin Endocrinol Metab. 2021; 106:e803–11.

13. Lui DT, Lee CH, Chow WS, Lee AC, Tam AR, Fong CH, et al. Thyroid dysfunction in relation to immune profile, disease status, and outcome in 191 patients with COVID-19. J Clin Endocrinol Metab. 2021; 106:e926–35.

14. China National Health Commission. Chinese clinical guidance for COVID-19 pneumonia diagnosis and treatment (7th edition) [Internet]. Chinese Society Cardiology;c2020. [cited 2021 May 10]. Available from: http://kjfy.meetingchina.org/msite/news/show/cn/3337.html .

15. QUANTA Lite TPO for in vitro diagnostic use (Laboratory reference manual). San Diego: INOVA Diagnostics Inc;2020.

16. Hung IF, Lung KC, Tso EY, Liu R, Chung TW, Chu MY, et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020; 395:1695–704.

17. RECOVERY Collaborative Group. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021; 384:693–704.

18. Tozzoli R, Bagnasco M, Giavarina D, Bizzaro N. TSH receptor autoantibody immunoassay in patients with Graves’ disease: improvement of diagnostic accuracy over different generations of methods: systematic review and meta-analysis. Autoimmun Rev. 2012; 12:107–13.

19. Caraccio N, Dardano A, Manfredonia F, Manca L, Pasquali L, Iudice A, et al. Long-term follow-up of 106 multiple sclerosis patients undergoing interferon-beta 1a or 1b therapy: predictive factors of thyroid disease development and duration. J Clin Endocrinol Metab. 2005; 90:4133–7.

20. Halpert G, Shoenfeld Y. SARS-CoV-2, the autoimmune virus. Autoimmun Rev. 2020; 19:102695.

21. Siriwardhane T, Krishna K, Ranganathan V, Jayaraman V, Wang T, Bei K, et al. Significance of anti-TPO as an early predictive marker in thyroid disease. Autoimmune Dis. 2019; 2019:1684074.

22. Desailloud R, Hober D. Viruses and thyroiditis: an update. Virol J. 2009; 6:5.

23. Akamine H, Takasu N, Komiya I, Ishikawa K, Shinjyo T, Nakachi K, et al. Association of HTLV-I with autoimmune thyroiditis in patients with adult T-cell leukaemia (ATL) and in HTLV-I carriers. Clin Endocrinol (Oxf). 1996; 45:461–6.

24. Antonelli A, Ferri C, Fallahi P, Ferrari SM, Ghinoi A, Rotondi M, et al. Thyroid disorders in chronic hepatitis C virus infection. Thyroid. 2006; 16:563–72.