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.

Background: Mounting evidence has revealed the interrelationship between thyroid and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to explain the thyroid dysfunction and autoimmune thyroid disorders observed after coronavirus disease 2019 (COVID-19). There are limited reports of thyroid dysfunction after SARS-CoV-2 vaccination.Methods: We report a case of a 40-year-old Chinese woman who developed Graves' disease after BNT162b2 mRNA vaccine. A search of PubMed and Embase databases from 1 September 2019 to 31 August 2021 was performed using the following keywords: “COVID,” “vaccine,” “thyroid,” “thyroiditis,” and “Graves.”Results: A 40-year-old Chinese woman who had 8-year history of hypothyroidism requiring thyroxine replacement. Her anti-thyroid peroxidase and anti-thyroglobulin antibodies were negative at diagnosis. She received her first and second doses of BNT162b2 mRNA vaccine on 6 April and 1 May 2021, respectively. She developed thyrotoxicosis and was diagnosed to have Graves' disease 5 weeks after the second dose of vaccine, with positive thyroid stimulating immunoglobulin level, diffuse goiter with hypervascularity on thyroid ultrasonography and diffusely increased thyroid uptake on technetium thyroid scan. Both anti-thyroid peroxidase and anti-thyroglobulin antibodies became positive. She was treated with carbimazole. Literature search revealed four cases of Graves' disease after SARS-CoV-2 vaccination, all after mRNA vaccines; and nine cases of subacute thyroiditis, after different types of SARS-CoV-2 vaccines.Conclusion: Our case represents the fifth in the literature of Graves' disease after SARS-CoV-2 vaccination, with an unusual presentation on a longstanding history of hypothyroidism. Clinicians should remain vigilant about potential thyroid dysfunction after SARS-CoV-2 vaccination in the current pandemic.

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.

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.

Purpose Thyroid dysfunction, including thyroiditis, is well recognized in COVID-19 patients. We evaluated thyroid ultrasonographic features among COVID-19 survivors, which are less well known. Methods Adult COVID-19 survivors without known thyroid disorders who attended dedicated COVID-19 clinic underwent thyroid ultrasonography and assessment of thyroid function and autoimmunity. Adults admitted for acute non-thyroidal surgical problems and negative for COVID-19 were recruited as control. SARS-CoV-2 viral load (VL) was presented as the inverse of cycle threshold values from the real-time reverse transcription-polymerase chain reaction of the respiratory specimen on admission. Results In total, 79 COVID-19 patients and 44 non-COVID-19 controls were included. All abnormal thyroid function tests during acute COVID-19 recovered upon follow-up. Thyroid ultrasonography was performed at a median of 67 days after acute COVID-19. The median thyroid volume was 9.73 mL (IQR: 7.87–13.70). In multivariable linear regression, SARS-CoV-2 VL on presentation (standardized beta −0.206, p = 0.042) inversely correlated with thyroid volume, in addition to body mass index at the time of ultrasonography ( p < 0.001). Sex-specific analysis revealed similar results among men but not women. Eleven COVID-19 patients (13.9%) had ultrasonographic changes suggestive of thyroiditis, comparable to non-COVID-19 patients ( p = 0.375). None of these 11 patients had isolated low thyroid-stimulating hormone levels suggestive of thyroiditis at initial admission or the time of ultrasonography. Conclusions Higher SARS-CoV-2 VL on presentation were associated with smaller thyroid volumes, especially in men. Further research is suggested to investigate this possible direct viral effect of SARS-CoV-2 on the thyroid gland. There was no increased rate of ultrasonographic features suggestive of thyroiditis in COVID-19 survivors.

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BackgroundBoth lymphopenia and thyroid dysfunction are commonly observed among COVID-19 patients. Whether thyroid function independently correlates with lymphocyte counts (LYM) remains to be elucidated.MethodsWe included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to April 2021 who had thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and LYM measured on admission.ResultsA total of 541 patients were included. Median LYM was 1.22 x 109/L, with 36.0% of the cohort lymphopenic. 83 patients (15.4%) had abnormal thyroid function tests (TFTs), mostly non-thyroidal illness syndrome (NTIS). Patients with lymphopenia had lower TSH, fT4 and fT3 levels than those without. Multivariable stepwise linear regression analysis revealed that both TSH (standardized beta 0.160, p&lt;0.001) and fT3 (standardized beta 0.094, p=0.023), but not fT4, remained independently correlated with LYM, in addition to age, SARS-CoV-2 viral load, C-reactive protein levels, coagulation profile, sodium levels and more severe clinical presentations. Among the 40 patients who had reassessment of TFTs and LYM after discharge, at a median of 9 days from admission, there were significant increases in TSH (p=0.031), fT3 (p&lt;0.001) and LYM (p&lt;0.001). Furthermore, patients who had both lymphopenia and NTIS were more likely to deteriorate compared to those who only had either one alone, and those without lymphopenia or NTIS (p for trend &lt;0.001).ConclusionTSH and fT3 levels showed independent positive correlations with LYM among COVID-19 patients, supporting the interaction between the hypothalamic-pituitary-thyroid axis and immune system in COVID-19.