Objective SARS-CoV-2-related thyroiditis is increasingly recognized. The role of thyroid autoimmunity and SARS-CoV-2 viral load in SARS-CoV-2-related thyroid dysfunction is unclear. We evaluated the thyroid function of a cohort of COVID-19 patients, in relation to their clinical features, biochemical, immunological and inflammatory markers. Methods Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for COVID-19 from 21 July to 21 August, 2020 were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine (fT3) and anti-thyroid antibodies were measured on admission. Results Among 191 patients with COVID-19 (mean age 53.5 ± 17.2 years; 51.8% male), 84.3% were mild, 12.6% were moderate, and 3.1% were severe. 13.1% had abnormal thyroid function. Ten patients had isolated low TSH, suggestive of subclinical thyrotoxicosis due to thyroiditis, although the contribution of autoimmunity was likely in two of them. Autoimmune thyroiditis probably also contributed to subclinical hypothyroidism in another patient. Ten patients had isolated low fT3, likely representing non-thyroidal illness syndrome. Lower SARS-Cov-2 PCR cycle threshold values and elevated C-reactive protein were independently associated with occurrence of low TSH (p=0.030) and low fT3 (p=0.007) respectively. A decreasing trend of fT3 with increasing COVID-19 severity (p=0.032) was found. Patients with low fT3 had more adverse COVID-19-related outcomes. Conclusion Around 15% of patients with mild to moderate COVID-19 had thyroid dysfunction. There may be a direct effect of SARS-CoV-2 on thyroid function, potentially leading to exacerbation of pre-existing autoimmune thyroid disease. Low fT3, associated with systemic inflammation, may have a prognostic significance.

Objective: Existing studies reported the potential prognostic role of non-thyroidal illness syndrome (NTIS), characterized by low triiodothyronine (T3) with normal/low thyroidstimulating hormone (TSH), mainly in severe COVID-19. None considered the significant impact of SARS-CoV-2 viral load on adverse outcomes. We aimed to clarify the prognostic role of NTIS among predominantly mild-to-moderate COVID-19 patients. Design: A prospective study of COVID-19 patients. Patients and Measurements: Consecutive adults admitted to Queen Mary Hospital for confirmed COVID-19 from July to December 2020 were prospectively recruited. SARS-CoV-2 viral load was represented by cycle threshold (Ct) values from real-time reverse transcription-polymerase chain reaction of the respiratory specimen on admission. Serum TSH, free thyroxine and free T3 were measured on admission. The outcome was deterioration in clinical severity, defined as worsening in ≥1 category of clinical severity according to the Chinese National Health Commission guideline.Results: We recruited 367 patients. At baseline, 75.2% had mild disease, and 27 patients (7.4%) had NTIS. Fifty-three patients (14.4%) had clinical deterioration. Patients with NTIS were older, had more comorbidities, worse symptomatology, higher SARS-CoV-2 viral loads and worse profiles of inflammatory and tissue injury markers. They were more likely to have clinical deterioration (p < .001). In multivariable stepwise logistic regression analysis, NTIS independently predicted clinical deterioration (adjusted odds ratio 3.19, p = .017), in addition to Ct value <25 (p < .001), elevated C-reactive protein (p = .004), age >50 years (p = .011) and elevated creatine kinase (p = .017).Conclusions: Non-thyroidal illness syndrome was not uncommon even in mild-tomoderate COVID-19 patients. NTIS on admission could predict clinical deterioration in COVID-19, independent of SARS-CoV-2 viral load, age and markers of inflammation and tissue injury. K E Y W O R D S COVID-19, euthyroid sick syndromes, prognosis, SARS-CoV-2, thyroid function tests, thyroid gland How to cite this article: Lui DTW, Lee CH, Chow WS, et al. Role of non-thyroidal illness syndrome in predicting adverse outcomes in COVID-19 patients predominantly of mild-tomoderate severity.

Objective Long COVID (LC) is an emerging global health issue. Fatigue is a common feature. Whether thyroid function and autoimmunity play a role is uncertain. We aimed to evaluate the prevalence and predictors of LC and the potential role of thyroid function and autoimmunity in LC. Methods We included consecutive adults without known thyroid disorder, admitted to a major COVID-19 centre for confirmed COVID-19 from July to December 2020 who had thyroid function tests (TFTs) and anti-thyroid antibodies measured on admission and at follow-up. LC was defined by the presence or persistence of symptoms upon follow-up. Results In total, 204 patients (median age: 55.0 years; 46.6% men) were reassessed at a median of 89 days (IQR: 69–99) after acute COVID-19. Forty-one (20.1%) had LC. Female (adjusted odds ratio [aOR] 2.48, p=0.018) and SARS-CoV-2 PCR cycle threshold value <25 on admission (aOR 2.84, p=0.012) independently predicted the occurrence of LC. Upon follow-up, most abnormal TFTs in acute COVID-19 resolved, and incident thyroid dysfunction was rare. Nonetheless, we observed incident anti-TPO (anti-thyroid peroxidase) positivity. While baseline or follow-up TFTs were not associated with the occurrence of LC, among 172 patients symptomatic in acute COVID-19, symptom resolution was more likely in those with positive anti-TPO upon follow-up (p=0.043). Conclusion LC is common among COVID-19 survivors, with female and those with higher viral load in acute COVID-19 particularly vulnerable. The observation of incident anti-TPO positivity warrants further follow-up for thyroid dysfunction. Whether anti-TPO plays a protective role in LC remains to be elucidated.