As of 20 August 2023, the coronavirus 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 760 million people worldwide and caused more than 6.9 million deaths.(1) Long COVID is a term coined for the long-term sequelae of acute SARS-CoV-2 infection. Long COVID includes not only persistent symptoms after acute COVID-19, but is also a multifaceted syndrome encompassing adverse outcomes in various organ systems.(2) It is clinically relevant to define the scope of the problem, which informs surveillance strategy among COVID-19 survivors.

Since angiotensin-converting enzyme 2 (ACE2) is expressed in many endocrine organs including the thyroid, the thyroid gland is a susceptible target of SARS-CoV-2 for both direct (due to ACE2 expression) and indirect damage (due to abnormal immune-inflammatory responses to SARS-CoV-2).(3, 4) There are also concerns that COVID-19 may trigger autoimmune disorders, including autoimmune thyroid disorders such as Graves’ disease and Hashimoto’s thyroiditis.(5) The effect of acute SARS-CoV-2 infection on the thyroid gland has been extensively studied and described. Non-thyroidal illness syndrome is the most prevalent and consistently reported thyroid function abnormalities in acute COVID-19.(6) In contrast, the long-term effect of SARS-CoV-2 infection on the risk of incident thyroid dysfunction is less well evaluated.

Several recent studies with longer follow-up of 6–12 months have investigated the effect of SARS-CoV-2 infection on incident thyroid function abnormalities and thyroid autoimmunity. A retrospective cohort study of 240 pregnant women followed up for glycaemic status postpartum showed that those with SARS-CoV-2 seropositivity had a comparable risk of thyroid dysfunction and new‐onset thyroid autoimmunity within 1 year to those without.(7) In a prospective 6-month follow-up study of 250 COVID-19 survivors, most abnormal thyroid function during acute SARS-CoV-2 infection resolved upon follow-up.(8) Incident thyroid function abnormalities occurred in 4.5% of the 199 patients with normal thyroid function in acute COVID-19, which were partly contributed by interferon beta-1b treatment in acute COVID-19.(9) However, none were clinically overt.(8) Notably, there was no significant change in the titres of anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) among the 129 patients with a complete 6-month follow-up. This suggests that COVID-19 is unlikely to induce significant thyroid autoimmunity.(8) Consistent findings were obtained in a similar 6-month follow-up study by Alphan-Uç et al.(10) Muller et al followed 75 COVID-19 survivors who had severe acute COVID-19 for up to one-year post-infection,(11) and found that all had normal thyroid function with normalisation of inflammatory markers. However, only 25 of them turned up at 1-year follow-up. There was also no change in anti-thyroid antibody positivity during follow-up. Nonetheless, the evidence of thyroid dysfunction in the post-acute phase of SARS-CoV-2 infection is limited by the relatively small sample size(7, 8, 10, 11) and the absence of a non-COVID control group.(8, 10, 11)

Hence, we performed a population-based cohort study to evaluate the risk of incident thyroid dysfunction among COVID-19 survivors in the post-acute phase.