Effect of inactivated and mRNA COVID-19 vaccination on thyroid function among patients treated for hyperthyroidism.

OBJECTIVE: Among patients treated for hyperthyroidism, we evaluated factors associated with not receiving COVID-19 vaccination and whether COVID-19 vaccination was associated with thyroid function instability. METHODS: We included consecutive patients treated for hyperthyroidism attending the Thyroid Clinic of a teaching hospital between January and September 2021. They were categorised into vaccinated and unvaccinated groups. The index date was the date of first-dose vaccination for vaccinated group, and the first date of attendance in the inclusion period for unvaccinated group. They were followed up until March 2022 or occurrence of thyroid function instability (worsening of thyroid function/increase in anti-thyroid drug dosage), whichever was earlier. RESULTS: 910 patients were included (mean age 51.6 years; 82.1% female). 86.2% had Graves' disease. 67.3% were vaccinated (67.3% BNT162b2; 30.6% CoronaVac; 2.1% heterologous). Abnormal thyroid function and cardiovascular comorbidities were independently associated with unvaccinated status. Upon median follow-up of 5.3 months, thyroid function instability occurred in 15.9% of patients. COVID-19 vaccination did not increase risks of thyroid function instability (HR 0.78, 95%CI 0.56-1.09, p = 0.151): consistent in Graves' disease, both types of vaccines, and regardless of whether baseline thyroid function was normal. Twenty-seven patients overtly thyrotoxic at the time of vaccination received COVID-19 vaccines without triggering thyroid storm or difficulty in subsequent thyroid function control. CONCLUSION: Among patients treated for hyperthyroidism, abnormal thyroid function was a factor predicting unvaccinated status. Our results should encourage patients treated for hyperthyroidism to receive COVID-19 vaccination to protect themselves from adverse outcomes and potential long-term sequelae of COVID-19.

A prospective follow-up of thyroid volume and thyroiditis features on ultrasonography among survivors of predominantly mild to moderate COVID-19.

Background: We previously showed that higher SARS-CoV-2 viral load correlated with smaller thyroid volumes among COVID-19 survivors at 2 months after acute COVID-19. Our current follow-up study evaluated the evolution of thyroid volumes and thyroiditis features within the same group of patients 6 months later. Methods: Adult COVID-19 survivors who underwent thyroid ultrasonography 2 months after infection (USG1) were recruited for follow-up USG 6 months later (USG2). The primary outcome was the change in thyroid volume. We also reassessed thyroiditis features on USG, thyroid function and anti-thyroid antibodies. Results: Fifty-four patients were recruited (mean age 48.1 years; 63% men). The mean thyroid volume increased from USG1 to USG2 (11.9 ± 4.8 to 14.5 ± 6.2 mL, p < 0.001). Thirty-two patients (59.3%) had significant increase in thyroid volume by ≥15%, and they had a median increase of +33.3% (IQR: +20.0% to +45.0%). Multivariable logistic regression analysis showed that only higher baseline SARS-CoV-2 viral load independently correlated with significant thyroid volume increase on USG2 (p = 0.022). Among the seven patients with thyroiditis features on USG1, six (85.7%) had the features resolved on USG2. None had new thyroiditis features on USG2. All abnormal thyroid function during acute COVID-19 resolved upon USG1 and USG2. Conclusion: Most COVID-19 survivors had an increase in thyroid volume from early convalescent phase to later convalescent phase. This increase correlated with high initial SARS-CoV-2 viral load. Together with the resolution of thyroiditis features, these may suggest a transient direct atrophic effect of SARS-CoV-2 on the thyroid gland with subsequent recovery of thyroid volume and thyroiditis features.

A prospective follow-up on thyroid function, thyroid autoimmunity and long COVID among 250 COVID-19 survivors.

PURPOSE: We evaluated the evolution of thyroid function and autoimmunity among COVID-19 survivors over 6 months in relation to interferon beta-1b treatment and long COVID. METHODS: We included COVID-19 survivors managed in a major COVID-19 centre between July 2020 and May 2021 who were reassessed three and/or six months after acute COVID-19. Thyroid function tests (TFTs) and anti-thyroid antibody titres were measured at acute COVID-19, 3-month and 6-month. RESULTS: 250 COVID-19 survivors were included (mean age 52.7 years, 50.4% men). Persistent thyroid function abnormalities were more likely in those with abnormal TFTs in acute COVID-19 (P < 0.001). Among 51 patients with abnormal TFTs in acute COVID-19, 82.4% resolved upon follow-up. Of 199 patients with normal TFTs in acute COVID-19, only 4.5% had incident abnormal TFTs, more likely in interferon-treated patients (P = 0.044) and none clinically overt. Among 129 patients with complete 6-month follow-up for anti-thyroid antibody titres, there was no significant change overall, except for modest increase in anti-thyroid antibody titres among the 84 interferon-treated patients (P < 0.05 at both 3 months and 6 months). Long COVID occurred in 19.5% and 10.4% at 3 and 6 months respectively, where TFTs and anti-thyroid antibody titres were not predictive of its occurrence. CONCLUSION: Over 6 months, most abnormal TFTs in acute COVID-19 resolved, with no significant incident thyroid dysfunction. SARS-CoV-2 infection did not lead to change in thyroid autoimmunity, while interferon treatment was associated with modest increase in anti-thyroid antibody titres. Thyroid function and anti-thyroid antibodies did not play a significant role in long COVID.

mRNA (BNT162b2) and Inactivated (CoronaVac) COVID-19 Vaccination and Risk of Adverse Events and Acute Diabetic Complications in Patients with Type 2 Diabetes Mellitus: A Population-Based Study.

INTRODUCTION: In Hong Kong, CoronaVac and BNT162b2 have been approved for emergency use owing to the coronavirus disease 2019 (COVID-19) pandemic. Reactions towards the vaccine and the risk of post-vaccination adverse events may be different between recipients with and without type 2 diabetes mellitus (T2DM). OBJECTIVE: The aim of this study was to evaluate the risk of adverse events of special interest (AESI) and acute diabetic complications in the T2DM population after COVID-19 vaccination in Hong Kong. RESEARCH DESIGN AND METHODS: Self-controlled case-series analysis was conducted. Patients with T2DM who received at least one dose of BNT162b2 or CoronaVac between 23 February 2021 and 31 January 2022 from electronic health records in Hong Kong were included. The incidence rates of 29 AESIs and acute diabetic complications (any of severe hypoglycemia, diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome) requiring hospitalization within 21 days after the first or second dose of vaccination were reported. The risks of these outcomes were evaluated using conditional Poisson regression. RESULTS: Among 141,224 BNT162b2 recipients and 209,739 CoronaVac recipients with T2DM, the incidence per 100,000 doses and incidence per 100,000 person-years of individual AESIs and acute diabetic complications ranged from 0 to 24.4 and 0 to 438.6 in BNT162b2 group, and 0 to 19.5 and 0 to 351.6 in CoronaVac group. We did not observe any significantly increased risk of individual AESIs or acute diabetic complications after first or second doses of BNT162b2 or CoronaVac vaccine. Subgroup analysis based on HbA1c < 7% and ≥ 7% also did not show significantly excess risk after vaccination. CONCLUSIONS: Patients with T2DM do not appear to have higher risks of AESI and acute diabetic complications after BNT162b2 or CoronaVac vaccination. Moreover, given the low incidence of AESIs and acute diabetic complications after vaccination, the absolute risk increment was likely minimal.

Comparing the B and T cell-mediated immune responses in patients with type 2 diabetes receiving mRNA or inactivated COVID-19 vaccines.

Acquiring protective immunity through vaccination is essential, especially for patients with type 2 diabetes who are vulnerable for adverse clinical outcomes during coronavirus disease 2019 (COVID-19) infection. Type 2 diabetes (T2D) is associated with immune dysfunction. Here, we evaluated the impact of T2D on the immunological responses induced by mRNA (BNT162b2) and inactivated (CoronaVac) vaccines, the two most commonly used COVID-19 vaccines. The study consisted of two parts. In Part 1, the sera titres of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) alpha receptor binding domain (RBD), their neutralizing capacity, and antigen-specific CD4+T and CD8+T cell responses at 3-6 months after vaccination were compared between BNT162b2 (n=60) and CoronaVac (n=50) vaccinees with or without T2D. Part 2 was a time-course study investigating the initial B and T cell responses induced by BNT162b2 among vaccinees (n=16) with or without T2D. Our data showed that T2D impaired both cellular and humoral immune responses induced by CoronaVac. For BNT162b2, T2D patients displayed a reduction in CD4+T-helper 1 (Th1) differentiation following their first dose. However, this initial defect was rectified by the second dose of BNT162b2, resulting in comparable levels of memory CD4+ and CD8+T cells, anti-RBD IgG, and neutralizing antibodies with healthy individuals at 3-6 months after vaccination. Hence, T2D influences the effectiveness of COVID-19 vaccines depending on their platform. Our findings provide a potential mechanism for the susceptibility of developing adverse outcomes observed in COVID-19 patients with T2D and received either CoronaVac or just one dose of BNT162b2.

Risk of thyroid dysfunction associated with mRNA and inactivated COVID-19 vaccines: a population-based study of 2.3 million vaccine recipients.

BACKGROUND: In view of accumulating case reports of thyroid dysfunction following COVID-19 vaccination, we evaluated the risks of incident thyroid dysfunction following inactivated (CoronaVac) and mRNA (BNT162b2) COVID-19 vaccines using a population-based dataset. METHODS: We identified people who received COVID-19 vaccination between 23 February and 30 September 2021 from a population-based electronic health database in Hong Kong, linked to vaccination records. Thyroid dysfunction encompassed anti-thyroid drug (ATD)/levothyroxine (LT4) initiation, biochemical picture of hyperthyroidism/hypothyroidism, incident Graves' disease (GD), and thyroiditis. A self-controlled case series design was used to estimate the incidence rate ratio (IRR) of thyroid dysfunction in a 56-day post-vaccination period compared to the baseline period (non-exposure period) using conditional Poisson regression. RESULTS: A total of 2,288,239 people received at least one dose of COVID-19 vaccination (57.8% BNT162b2 recipients and 42.2% CoronaVac recipients). 94.3% of BNT162b2 recipients and 92.2% of CoronaVac recipients received the second dose. Following the first dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.864, 95% CI 0.670-1.114; CoronaVac: IRR 0.707, 95% CI 0.549-0.912), LT4 initiation (BNT162b2: IRR 0.911, 95% CI 0.716-1.159; CoronaVac: IRR 0.778, 95% CI 0.618-0.981), biochemical picture of hyperthyroidism (BNT162b2: IRR 0.872, 95% CI 0.744-1.023; CoronaVac: IRR 0.830, 95% CI 0.713-0.967) or hypothyroidism (BNT162b2: IRR 1.002, 95% CI 0.838-1.199; CoronaVac: IRR 0.963, 95% CI 0.807-1.149), GD, and thyroiditis. Similarly, following the second dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.972, 95% CI 0.770-1.227; CoronaVac: IRR 0.879, 95%CI 0.693-1.116), LT4 initiation (BNT162b2: IRR 1.019, 95% CI 0.833-1.246; CoronaVac: IRR 0.768, 95% CI 0.613-0.962), hyperthyroidism (BNT162b2: IRR 1.039, 95% CI 0.899-1.201; CoronaVac: IRR 0.911, 95% CI 0.786-1.055), hypothyroidism (BNT162b2: IRR 0.935, 95% CI 0.794-1.102; CoronaVac: IRR 0.945, 95% CI 0.799-1.119), GD, and thyroiditis. Age- and sex-specific subgroup and sensitivity analyses showed consistent neutral associations between thyroid dysfunction and both types of COVID-19 vaccines. CONCLUSIONS: Our population-based study showed no evidence of vaccine-related increase in incident hyperthyroidism or hypothyroidism with both BNT162b2 and CoronaVac.

Effect of COVID-19 Vaccines on Thyroid Function and Autoimmunity and Effect of Thyroid Autoimmunity on Antibody Response.

CONTEXT: There are concerns for COVID-19 vaccination in triggering thyroid autoimmunity and causing thyroid dysfunction. Also, data on the effect of preexisting thyroid autoimmunity on the efficacy of COVID-19 vaccination are limited. OBJECTIVES: We evaluated the effect of COVID-19 vaccination on thyroid function and antibodies, and the influence of preexisting thyroid autoimmunity on neutralizing antibody (NAb) responses. METHODS: Adults without a history of COVID-19/thyroid disorders who received the COVID-19 vaccination during June to August 2021 were recruited. All received 2 doses of vaccines. Thyrotropin (TSH), free thyroxine (fT4), free 3,5,3'-triiodothyronine (fT3), antithyroid peroxidase (anti-TPO), and antithyroglobulin (anti-Tg) antibodies were measured at baseline and 8 weeks post vaccination. NAb against SARS-CoV-2 receptor-binding domain was measured. RESULTS: A total of 215 individuals were included (129 [60%] BNT162b2; 86 [40%] CoronaVac recipients): mean age 49.6 years, 37.2% men, and 12.1% anti-TPO/Tg positive at baseline. After vaccination, TSH did not change (P = .225), but fT4 slightly increased (from 12.0 ±â€…1.1 to 12.2 ±â€…1.2 pmol/L [from 0.93 ±â€…0.09 to 0.95 ±â€…0.09 ng/dL], P < .001) and fT3 slightly decreased (from 4.1 ±â€…0.4 to 4.0 ±â€…0.4 pmol/L [from 2.67 ±â€…0.26 to 2.60 ±â€…0.26 pg/mL], P < .001). Only 3 patients (1.4%) had abnormal thyroid function post vaccination, none clinically overt. Anti-TPO and anti-Tg titers increased modestly after vaccination (P < .001), without statistically significant changes in anti-TPO/Tg positivity. Changes in thyroid function and antithyroid antibodies were consistent between BNT162b2 and CoronaVac recipients, except for greater anti-TPO titer increase post BNT162b2 (P < .001). NAb responses were similar between individuals with and without preexisting thyroid autoimmunity (P = .855). CONCLUSION: COVID-19 vaccination was associated with a modest increase in antithyroid antibody titers. Anti-TPO increase was greater among BNT162b2 recipients. However, there was no clinically significant thyroid dysfunction post vaccination. NAb responses were not influenced by preexisting thyroid autoimmunity. Our results provide important reassurance for people to receive the COVID-19 vaccination.

Safety of Inactivated and mRNA COVID-19 Vaccination Among Patients Treated for Hypothyroidism: A Population-Based Cohort Study.

Background: Thyroiditis and Graves' disease have been reported after coronavirus disease 2019 (COVID-19) vaccination. We evaluated the risks of adverse events after COVID-19 vaccination among patients treated for hypothyroidism. Methods: In this retrospective population-based cohort study of Hong Kong Hospital Authority electronic health records with the Department of Health vaccination records linkage, levothyroxine (LT4) users were categorized into unvaccinated, vaccinated with BNT162b2 (mRNA vaccine), or CoronaVac (inactivated vaccine) between February 23, 2021, and September 9, 2021. Study outcomes were dosage reduction or escalation in LT4, emergency department (ED) visit, unscheduled hospitalization, adverse events of special interest (AESI) according to the World Health Organization's Global Advisory Committee on Vaccine Safety, and all-cause mortality. Inverse probability of treatment weighting for propensity score was applied to balance baseline patient characteristics among the three groups. Hazard ratios (HR) were estimated using Cox regression models. Patients were observed from the index date until the occurrence of study outcome, death, or censored on September 30, 2021, whichever came first. Results: In total, 47,086 LT4 users were identified (BNT162b2: n = 12,310; CoronaVac: n = 11,353; and unvaccinated: n = 23,423). COVID-19 vaccination was not associated with increased risks of LT4 dosage reduction (BNT162b2: HR = 0.971 [confidence interval; CI 0.892-1.058]; CoronaVac: HR = 0.968 [CI 0.904-1.037]) or escalation (BNT162b2: HR = 0.779 [CI 0.519-1.169]; CoronaVac: HR = 0.715 [CI 0.481-1.062]). Besides, COVID-19 vaccination was not associated with a higher risk of ED visits (BNT162b2: HR = 0.944 [CI 0.700-1.273]; CoronaVac: HR = 0.851 [CI 0.647-1.120]) or unscheduled hospitalization (BNT162b2: HR = 0.905 [CI 0.539-1.520]; CoronaVac: HR = 0.735 [CI 0.448-1.207]). There were two (0.016%) deaths and six (0.062%) AESI recorded for BNT162b2 recipients, and one (0.009%) and three (0.035%) for CoronaVac recipients, respectively. Conclusions: BNT162b2 or CoronaVac vaccination is not associated with unstable thyroid status or an increased risk of adverse outcomes among patients treated for hypothyroidism in general. These reassuring data should encourage them to get vaccinated against COVID-19 for protection from potentially worse COVID-19-related outcomes.

A prospective study of the impact of glycaemic status on clinical outcomes and anti-SARS-CoV-2 antibody responses among patients with predominantly non-severe COVID-19.

AIMS: We carried out this prospective study of predominantly non-severe COVID-19 patients, to evaluate the influence of glycaemic status on clinical outcomes and neutralising antibody (Nab) responses, potentially relevant to the COVID-19 vaccination programme. METHODS: We included consecutive adults admitted to Queen Mary Hospital for COVID-19 from July 2020-May 2021. Glycaemic status was defined by admission HbA1c. Clinical deterioration was defined by radiological progression/new oxygen requirement/intensive care requirement/death. COVID-19 survivors had Nab measurements at 1-month, 2-month, 3-month and 6-month post-discharge. RESULTS: Among 605 patients (96.9% non-severe COVID-19; 325 normoglycaemia, 185 prediabetes, 95 diabetes), 74 (12.2%) had clinical deterioration, more likely with worse glycaemic status and higher HbA1c (p < 0.001). Older age (p < 0.001), higher viral loads (p < 0.001), higher C-reactive protein (CRP) (p < 0.001) and symptomatic presentation (p = 0.008), but not glycaemic status/HbA1c, independently predicted clinical deterioration. Older age (p = 0.001), higher CRP (p = 0.038), elevated lactate dehydrogenase (p = 0.046) and interferon treatment (p = 0.001), but not glycaemic status/HbA1c, independently predicted Nab titres. Rate of Nab titre decline was comparable across glycaemic status. CONCLUSIONS: COVID-19 patients with worse glycaemic status were more likely to deteriorate clinically, mediated through the association of worse glycaemic status with older age, more severe inflammation and higher viral loads. Importantly, Nab responses did not differ across glycaemic status.

The Independent Association of TSH and Free Triiodothyronine Levels With Lymphocyte Counts Among COVID-19 Patients.

Background: Both lymphopenia and thyroid dysfunction are commonly observed among COVID-19 patients. Whether thyroid function independently correlates with lymphocyte counts (LYM) remains to be elucidated. Methods: We 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. Results: A 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<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<0.001) and LYM (p<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 <0.001). Conclusion: TSH 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.

Development of Graves' Disease After SARS-CoV-2 mRNA Vaccination: A Case Report and Literature Review.

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.

The Impact of Interferon Beta-1b Therapy on Thyroid Function and Autoimmunity Among COVID-19 Survivors.

Background: Some studies have indicated that interferon (IFN) may be valuable in COVID-19. We aimed to evaluate the impact of short-term IFN on incident thyroid dysfunction and autoimmunity among COVID-19 survivors. Methods: We included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to January 2021 who had thyroid function tests (TFTs) and anti-thyroid antibodies measured both on admission and at three months. Results: 226 patients were included (median age 55.0 years; 49.6% men): 135 were IFN-treated. There tended to be more abnormal TFTs upon reassessment in IFN-treated patients (8.1% vs 2.2%, p=0.080). 179 patients (65.4% IFN-treated) had a complete reassessment of anti-thyroid antibodies. There were significant increases in titres of both anti-thyroid peroxidase antibodies (anti-TPO: baseline 29.21 units [IQR: 14.97 - 67.14] vs reassessment 34.30 units [IQR: 18.82 - 94.65], p<0.001) and anti-thyroglobulin antibodies (anti-Tg: baseline 8.23 units [IQR: 5.40 - 18.44] vs reassessment 9.14 units [IQR: 6.83 - 17.17], p=0.001) in the IFN-treated group but not IFN-naïve group. IFN treatment (standardised beta 0.245, p=0.001) was independently associated with changes in anti-TPO titre. Of the 143 patients negative for anti-TPO at baseline, 8 became anti-TPO positive upon reassessment (seven IFN-treated; one IFN-naïve). Incident anti-TPO positivity was more likely to be associated with abnormal TFTs upon reassessment (phi 0.188, p=0.025). Conclusion: IFN for COVID-19 was associated with modest increases in anti-thyroid antibody titres, and a trend of more incident anti-TPO positivity and abnormal TFTs during convalescence. Our findings suggest that clinicians monitor the thyroid function and anti-thyroid antibodies among IFN-treated COVID-19 survivors, and call for further follow-up studies regarding the clinical significance of these changes.

Higher SARS-CoV-2 viral loads correlated with smaller thyroid volumes on ultrasound among male 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.

One year into the clash of pandemics of diabetes and COVID-19: Lessons learnt and future perspectives.

There is a bidirectional relationship between coronavirus disease 2019 (COVID-19) and diabetes. Furthermore, the COVID-19 pandemic has catalyzed the use of technology in diabetes care. Future research is required to assess the impact of COVID-19 on new-onset diabetes and the influence of diabetes on responses to COVID-19 vaccines.

Long COVID in Patients With Mild to Moderate Disease: Do Thyroid Function and Autoimmunity Play a Role?

OBJECTIVE: Post-acute sequelae of coronavirus disease 2019 (COVID-19) or 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 a known thyroid disorder who were admitted to a major COVID-19 center for confirmed COVID-19 from July to December 2020. Thyroid function tests and antithyroid antibodies were measured for all patients 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; 95 men [46.6%]) were reassessed at a median of 89 days (interquartile range, 69-99) after acute COVID-19. Of the 204 patients, 41 (20.1%) had LC. Female sex (adjusted odds ratio, 2.48; P = .018) and severe acute respiratory syndrome coronavirus 2 polymerase chain reaction cycle threshold value of <25 on admission (adjusted odds ratio, 2.84; P = .012) independently predicted the occurrence of LC. Upon follow-up, most abnormal thyroid function tests in acute COVID-19 resolved, and incident thyroid dysfunction was rare. Nonetheless, we observed incident antithyroid peroxidase (anti-TPO) positivity. Although baseline or follow-up thyroid function tests were not associated with the occurrence of LC, among 172 patients with symptomatic acute COVID-19, symptom resolution was more likely in those with positive anti-TPO upon follow-up (P = .043). CONCLUSION: LC is common among COVID-19 survivors, with females and those with higher viral load in acute COVID-19 particularly being 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.

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

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.

Role of non-thyroidal illness syndrome in predicting adverse outcomes in COVID-19 patients predominantly of mild-to-moderate severity.

OBJECTIVE: Existing studies reported the potential prognostic role of non-thyroidal illness syndrome (NTIS), characterized by low triiodothyronine (T3) with normal/low thyroid-stimulating 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-to-moderate 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.

Thyroid Dysfunction in Relation to Immune Profile, Disease Status, and Outcome in 191 Patients with COVID-19.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (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 coronavirus disease 2019 (COVID-19) patients, in relation to their clinical features, and biochemical, immunological, and inflammatory markers. METHODS: Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for COVID-19 from July 21 to August 21, 2020, were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine (fT3), and antithyroid antibodies were measured on admission. RESULTS: Among 191 patients with COVID-19 (mean age 53.5 ±â€…17.2 years; 51.8% male), 84.3% were mild, 12.6% were moderate, and 3.1% were severe. Abnormal thyroid function was seen in 13.1%. Ten patients had isolated low TSH, suggestive of subclinical thyrotoxicosis due to thyroiditis, although the contribution of autoimmunity was likely in 2 of them. Autoimmune thyroiditis probably also contributed to subclinical hypothyroidism in another patient. Ten patients had isolated low fT3, likely representing nonthyroidal illness syndrome. Lower SARS-Cov-2 polymerase chain reaction cycle threshold values and elevated C-reactive protein were independently associated with occurrence of low TSH (P = .030) and low fT3 (P = .007), respectively. A decreasing trend of fT3 with increasing COVID-19 severity (P = .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.