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.

OBJECTIVE Preclinical studies have suggested that thrombospondin-2 (TSP2) is implicated in liver fibrosis. However, the clinical relevance of TSP2 in nonalcoholic fatty liver disease (NAFLD) remains undefined. Here, we investigated the cross-sectional and longitudinal associations of circulating TSP2 levels with advanced fibrosis (F3 or greater [≥FE] fibrosis) in NAFLD. RESEARCH DESIGN AND METHODS Serum TSP2 levels were measured in 820 patients with type 2 diabetes and NAFLD. All participants received vibration-controlled transient elastography (VCTE) at baseline to evaluate their hepatic steatosis and fibrosis using controlled attenuation parameter (CAP) and liver stiffness (LS) measurements, respectively. Among those without advanced fibrosis at baseline, reassessment VCTE was performed to determine whether ≥F3 fibrosis had developed over time. Multivariable logistic regression analysis was used to evaluate the cross-sectional and longitudinal associations of serum TSP2 level with ≥F3 fibrosis. RESULTS Baseline serum TSP2 level was independently associated with the presence of ≥F3 fibrosis (odds ratio [OR] 5.13, P &lt; 0.001). The inclusion of serum TSP2 level significantly improved the identification of ≥F3 fibrosis by clinical risk factors. Over a median follow-up of 1.5 years, 8.8% developed ≥F3 fibrosis. Baseline serum TSP2 level was significantly associated with incident ≥F3 fibrosis (OR 2.82, P = 0.005), independent of other significant clinical risk factors of fibrosis progression, including BMI, platelet count, and CAP at baseline. CONCLUSIONS Circulating TSP2 level was associated with both the presence and the development of advanced fibrosis and might be a potentially useful prognostic biomarker for the development and progression of liver fibrosis in patients with type 2 diabetes and NAFLD.

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.

The global prevalence of non‐alcoholic fatty liver disease (NAFLD) is rising, along with the epidemic of diabesity. NAFLD is present in >70% of individuals with type 2 diabetes. Although the mutually detrimental relationship between NAFLD and type 2 diabetes has been well established, a multitude of recent studies have further shown that type 2 diabetes is closely linked to the development of cirrhosis, hepatocellular carcinoma, liver‐related morbidity and mortality. In contrast, NAFLD also negatively impacts type 2 diabetes both in terms of its incidence and related adverse clinical outcomes, including cardiovascular and chronic kidney diseases. In response to these global health threats, clinical care pathways for NAFLD and guidelines for metabolic dysfunction‐associated fatty liver disease have been developed. Several antidiabetic agents have been evaluated for their potential hepatic benefits with promising results. Furthermore, type 2 diabetes patients are increasingly represented in clinical trials of novel therapeutics for NAFLD. However, despite the wealth of knowledge in NAFLD and type 2 diabetes, lack of awareness of the disease and the potential weight of this problem remains a major challenge, especially among clinicians who are outside the field of hepatology and gastroenterology. This review therefore aimed to provide all diabetes care providers with a summary of the latest evidence that supports NAFLD as an emerging diabetic complication of increasing importance, and to present the current recommendations, focusing on the assessment and therapeutic strategies, on the management of NAFLD among type 2 diabetes patients.