The Spectrum of Thyroid Function Tests and Autoantibodies During Hospitalization and After Six Months of Discharge in COVID-19 Patients: Does COVID-19 Trigger Autoimmunity?

OBJECTIVE: The aim of the study was to investigate thyroid function test (TFT) results and anti-thyroid antibody titers in acutely infected COVID-19 patients, as well as the changes in TFT and autoantibody results during the 6-months recovery period among survivors. PATIENTS AND DESIGN: A total of 163 adult COVID-19 patients and 124 COVID-19 survivors were evaluated in terms of TFT (thyroid stimulating hormone [TSH], free triiodothyronine [fT3], and free thyroxine [fT4]) and anti-thyroid antibodies (anti-thyroglobulin [anti-Tg] and anti-thyroid peroxidase [anti-TPO]). RESULTS: Thyroid dysfunction was noted in 56.4% of patients on admission, including the non-thyroidal illness syndrome (NTIS) in most cases. Presence vs. absence of thyroid dysfunction on admission was associated with significantly higher rate of severe disease (p < 0.001), while severe vs. mild-to-moderate disease was associated with significantly lower serum fT3 levels (p = 0.001). Overall, 94.4% of survivors were euthyroid at the time of 6 months post-discharge, while in some patients, the post-COVID-19 recovery period was also associated with significantly increased anti-TPO titers and the presence of new-onset or persistent subclinical hypothyroidism. CONCLUSION: This is one of the few studies to evaluate TFT and autoantibodies over a 6-month period after recovery from COVID-19. The presence of emergent or persistent subclinical hypothyroidism and the significantly increased anti-TPO titers in some patients during the convalescence period suggest the need for follow-up for development of thyroid dysfunction and autoimmunity among COVID-19 survivors.

Study of thyroid function among COVID-19-affected and non-affected people during pre and post-vaccination.

The novel coronavirus COVID-19 has caused a global pandemic with many long-ranging effects on the physiological balance of the human body. The impact of COVID-19 on the thyroid axis remains uncertain. Our aim was to assess the long-term consequences of COVID-19 infection and its vaccination with thyroid hormones. Thirty laboratory-confirmed COVID-19-positive patients with no vaccination record, thirty COVID-19-negative patients with vaccination records, and ten healthy subjects were retrospectively, and cross-sectionally enrolled in this study. An ELISA assay was performed to evaluate thyroid function tests, including the total triiodothyronine (TT3), total thyroxine (TT4), and thyroid stimulating hormone (TSH). We found decreased levels of TT3, average or low plasma T4 levels, and standard or slightly decreased TSH levels in unvaccinated COVID-19-positive patients than in the healthy group, while the vaccinated COVID-19-negative group had normal thyroid hormone levels compared to controls. The correlation between TT3 and TSH levels gradually shifted from no association to a negative pattern in the unvaccinated COVID-19-positive group. Again, a highly significant negative correlation between TSH and TT3 was observed on days above 150, although a slight fluctuation was noted on day 90. This pilot study from Bangladesh shows that abnormalities in thyroid function can be observed during COVID-19 infection and after vaccination, which gradually recovers over time.

Development of a prediction score (ThyroCOVID) for identifying abnormal thyroid function in COVID-19 patients.

PURPOSE: Thyroid dysfunction in COVID-19 carries clinical and prognostic implications. In this study, we developed a prediction score (ThyroCOVID) for abnormal thyroid function (TFT) on admission amongst COVID-19 patients. METHODS: Consecutive COVID-19 patients admitted to Queen Mary Hospital were prospectively recruited during July 2020-May 2021. Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were measured on admission. Multivariable logistic regression analysis was performed to identify independent determinants of abnormal TFTs. ThyroCOVID was developed based on a clinical model with the lowest Akaike information criteria. RESULTS: Five hundred and forty six COVID-19 patients were recruited (median age 50 years, 45.4% men, 72.9% mild disease on admission). 84 patients (15.4%) had abnormal TFTs on admission. Patients with abnormal TFTs were more likely to be older, have more comorbidities, symptomatic, have worse COVID-19 severity, higher SARS-CoV-2 viral loads and more adverse profile of acute-phase reactants, haematological and biochemical parameters. ThyroCOVID consisted of five parameters: symptoms (malaise), comorbidities (ischaemic heart disease/congestive heart failure) and laboratory parameters (lymphocyte count, C-reactive protein, and SARS-CoV-2 cycle threshold values). It was able to identify abnormal TFT on admission with an AUROC of 0.73 (95% CI 0.67-0.79). The optimal cut-off of 0.15 had a sensitivity of 75.0%, specificity of 65.2%, negative predictive value of 93.5% and positive predictive value of 28.1% in identifying abnormal TFTs on admission amongst COVID-19 patients. CONCLUSION: ThyroCOVID, a prediction score to identify COVID-19 patients at risk of having abnormal TFT on admission, was developed based on a cohort of predominantly non-severe COVID-19 patients.

Serum Concentrations of Thyroid-Stimulating Hormone, Triiodothyronine, and Thyroxine in Outpatients Infected with SARS-CoV2 in Khuzestan Province, Iran: A Disease Clinical Course Approach.

Background and Objectives: The virus SARS-CoV2, which causes COVID-19, affects the endocrine system. This study investigated serum concentrations of the thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) in 53 outpatients infected with SARS-CoV2 and 53 non-infected matched participants in Khuzestan Province, Iran. We also examined the possible association of clinical symptoms progression and disease severity with serum concentrations of TSH, T3, and T4. Materials and Methods: A checklist was applied to collect demographic and clinical data. Blood samples were taken for biochemical analysis of serum concentrations of TSH, T3, and T4. Clinical symptoms of the infected outpatients were monitored weekly for 28 days. Results: Our results indicated that, as the severity of the disease increased, the respiratory and pulse rates raised significantly. Additionally, disease severity was significantly different between genders. Specifically, 79.5% of the asymptomatic/mild, and 38.5% of moderate outpatients were men. We also found significantly lower serum T3 but higher T4 in infected outpatients, compared with controls. However, serum TSH did not significantly differ between the two groups. The generalized estimating equation (GEE) analysis revealed no relationship between clinical symptoms progression and disease severity with serum concentrations of TSH, T3, and T4 in our study population. Additionally, GEE analysis showed that the odds ratio of neurological symptoms among women was 2.5 times that of men, the odds ratio of neurological symptoms in illiterates was 10 times higher than that of those without a high-school diploma, and the chance of developing pulmonary symptoms in those without high-school diploma was about 21 times higher than illiterates. Conclusion: In conclusion, this study showed that infected outpatients had significantly lower serum T3 but higher T4 than non-infected participants. There was no relation between symptom progression and disease severity with serum concentrations of TSH, T3, and T4, but educational status and sex significantly affected the chance of neurological and pulmonary symptoms occurring over 28 days. Our results may be used to develop potential therapies to treat COVID-19 disease.

The Potential of Thyroid Hormone Therapy in Severe COVID-19: Rationale and Preliminary Evidence.

Tissue hypoxia is one of the main pathophysiologic mechanisms in sepsis and particularly in COVID-19. Microvascular dysfunction, endothelialitis and alterations in red blood cell hemorheology are all implicated in severe COVID-19 hypoxia and multiorgan dysfunction. Tissue hypoxia results in tissue injury and remodeling with re-emergence of fetal programming via hypoxia-inducible factor-1α (HIF-1a)-dependent and -independent pathways. In this context, thyroid hormone (TH), a critical regulator of organ maturation, may be of relevance in preventing fetal-like hypoxia-induced remodeling in COVID-19 sepsis. Acute triiodothyronine (T3) treatment can prevent cardiac remodeling and improve recovery of function in clinical settings of hypoxic injury as acute myocardial infarction and by-pass cardiac surgery. Furthermore, T3 administration prevents tissue hypoxia in experimental sepsis. On the basis of this evidence, the use of T3 treatment was proposed for ICU (Intensive Care Unit) COVID-19 patients (Thy-Support, NCT04348513). The rationale for T3 therapy in severe COVID-19 and preliminary experimental and clinical evidence are discussed in this review.

Analysis of thyroid function in Japanese patients with coronavirus disease 2019.

Thyroid dysfunction that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is becoming increasingly recognized. However, only a few reports in Japan have addressed this issue to date. In this study, we sought to clarify whether infection with SARS-CoV-2 affected thyroid hormone levels and whether these hormones could be better predictors of prognosis in patients with coronavirus disease 2019 (COVID-19). Accordingly, we retrospectively examined 147 cases wherein thyroid hormones were measured at the time of admission among 848 Japanese patients with COVID-19 admitted to the Hyogo Prefectural Kakogawa Medical Center. All patients underwent thyroid function testing upon hospital admission. More than half (59.1%) of the patients were euthyroid. Twenty-four percent of patients had serum thyroid-stimulating hormone (TSH) levels lower than the reference range with normal serum free thyroxine (fT4) levels, and 3.4% of the patients had low TSH with high fT4 levels. Over 70% of the patients with moderate and severe COVID-19 had low serum free triiodothyronine (fT3) levels. Serum TSH and fT3 levels were inversely correlated with disease severity. The mortality rate in patients with low serum fT3 levels was significantly higher than that in those with normal serum fT3 levels.

The potential impact of COVID-19 on thyroid gland volumes among COVID-19 survivors.

PURPOSE: Data about the effects of COVID-19 on the endocrine system are increasing over time. In the present study, we investigated the effects of COVID-19 on the thyroid gland among COVID-19 survivors by comparing them with healthy subjects. METHODS: Adult COVID-19 survivors who were managed and followed up in the Infectious Disease clinic were asked to participate in this study. COVID-19 survivors were recruited via a convenience sampling and those who agreed to participate in this study were seen by endocrinologists for assessments. The blood tests were obtained for thyroid antibodies and thyroid function tests. Thyroid ultrasonography (USG) was done by the same physician. The ellipsoid formula was used for the calculation of thyroid gland volume. RESULTS: 64 adult COVID-19 survivors and 70 control subjects were enrolled in the study. The COVID-19 survivors were evaluated at median 5.7 months (IQR: 4-6.5) (range: 2-7 months) after acute infection. The mean thyroid gland volume was significantly lower in COVID-19 survivors (10.3 ± 3.4 mL) than in the controls (14 ± 5.3 mL) (p = 0.001). There was no significant difference in free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels between the groups. Among the twelve patients who had thyroid function evaluated in acute COVID-19, fT3 values were lower in acute COVID-19 than at the time of USG evaluation (3.04 ± 0.41 vs 3.47 ± 0.31 pg/mL), (p = 0.02). Among COVID-19 survivors, mild TSH elevation was detected in 4 (6.2%) patients and all of the other COVID-19 survivors (93.7%) were euthyroid. CONCLUSIONS: At 6 months after acute COVID, COVID-19 survivors had smaller thyroid gland volume than healthy controls, and only a few of the COVID-19 survivors had abnormal thyroid function.

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.

A Prospective Observational Study of 42 Patients with COVID-19 infection and a History of Hepatitis C Virus Infection and Thyroid Disease with Follow-Up Thyroid Function and Autoantibody Testing.

BACKGROUND Thyroiditis is an important extrahepatic association in chronic hepatitis C virus (HCV) infection. There have been reports of an association between SARS-CoV-2 infection and the onset or re-activation of autoimmune hypothyroidism. Therefore, we performed this prospective observational study of 42 patients with COVID-19 infection and a history of hepatitis C virus infection and thyroid disease with follow-up thyroid function and autoantibody testing. MATERIAL AND METHODS From April 2020 to October 2020, we performed a prospective observational study of patients with cured hepatitis C virus (HCV) infection and documented thyroid disease who became infected with SARS-CoV-2 (confirmed by SARS-CoV-2 RNA detection via reverse-transcription polymerase chain reaction [RT-PCT] from the upper respiratory tract, both nasal and pharyngeal swabs). Evaluation at 1 and 3 months after SARS-CoV-2 infection included serum determination of antithyroid antibodies (anti-thyroglobulin [anti-Tg] and antithyroid peroxidase [ATPO]), thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and evaluation of thyroid medication, with dose adjustment if required. RESULTS One-month follow-up showed that both patients with autoimmune thyroiditis as well as patients without antibodies had increased ATPO levels. Also, levels of TSH, fT3, and fT4 were significantly decreased. At 3-month follow-up, levels of ATPO were decreased in all patient groups and the levels of thyroid hormones increased to normal values. CONCLUSIONS This study supports previous reports of an association between SARS-CoV-2 infection and thyroid dysfunction associated with thyroid autoantibodies. Thyroid function tests may be considered as part of the laboratory work-up in patients with COVID-19.

Acute triiodothyronine treatment and red blood cell sedimentation rate (ESR) in critically ill COVID-19 patients: A novel association?

Sepsis and septic shock result in impaired microcirculation and red blood cell rheology which lead to tissue hypoxia and multi-organ failure. Early administration of triiodothyronine prevents tissue hypoxia in experimental sepsis. In this context, a clinical trial was initiated to test the efficacy of acute triiodothyronine administration to combat tissue hypoxia in critically ill COVID19 patients. Here, we provide preliminary data from interim analysis of this study showing a novel acute effect of triiodothyronine on erythrocyte sedimentation rate which may have an important therapeutic impact on red blood cell rheology and tissue hypoxia in sepsis and particular in COVID19 critical illness.Trial registration: ClinicalTrials.gov, NCT04348513. Registered 16 April 2020, https://clinicaltrials.gov/ct2/show/NCT04348513.

Nonthyroidal illness syndrome (NTIS) in severe COVID-19 patients: role of T3 on the Na/K pump gene expression and on hydroelectrolytic equilibrium.

BACKGROUND: Nonthyroidal Illness Syndrome (NTIS) can be detected in many critical illnesses. Recently, we demonstrated that this condition is frequently observed in COVID-19 patients too and it is correlated with the severity the disease. However, the exact mechanism through which thyroid hormones influence the course of COVID-19, as well as that of many other critical illnesses, is not clear yet and treatment with T4, T3 or a combination of both is still controversial. Aim of this study was to analyze body composition in COVID-19 patients in search of possible correlation with the thyroid function. METHODS AND FINDINGS: We report here our experience performed in 74 critically ill COVID-19 patients hospitalized in the intensive care unit (ICU) of our University Hospital in Rome. In these patients, we evaluated the thyroid hormone function and body composition by Bioelectrical Impedance Analysis (BIA) during the acute phase of the disease at admission in the ICU. To examine the effects of thyroid function on BIA parameters we analyzed also 96 outpatients, affected by thyroid diseases in different functional conditions. We demonstrated that COVID-19 patients with low FT3 serum values exhibited increased values of the Total Body Water/Free Fat Mass (TBW/FFM) ratio. Patients with the lowest FT3 serum values had also the highest level of TBW/FFM ratio. This ratio is an indicator of the fraction of FFM as water and represents one of the best-known body-composition constants in mammals. We found an inverse correlation between FT3 serum values and this constant. Reduced FT3 serum values in COVID-19 patients were correlated with the increase in the total body water (TBW), the extracellular water (ECW) and the sodium/potassium exchangeable ratio (Nae:Ke), and with the reduction of the intracellular water (ICW). No specific correlation was observed in thyroid patients at different functional conditions between any BIA parameters and FT3 serum values, except for the patient with myxedema, that showed a picture similar to that seen in COVID-19 patients with NTIS. Since the Na+/K+ pump is a well-known T3 target, we measured the mRNA expression levels of the two genes coding for the two major isoforms of this pump. We demonstrated that COVID-19 patients with NTIS had lower levels of mRNA of both genes in the peripheral blood mononuclear cells (PBMC)s obtained from our patients during the acute phase of the disease. In addition, we retrieved data from transcriptome analysis, performed on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM)s treated with T3 and we demonstrated that in these cells T3 is able to stimulate the expression of these two genes in a dose-dependent manner. CONCLUSIONS: In conclusion, we demonstrated that measurement of BIA parameters is a useful method to analyze water and salt retention in COVID-19 patients hospitalized in ICU and, in particular, in those that develop NTIS. Our results indicate that NTIS has peculiar similarities with myxedema seen in severe hypothyroid patients, albeit it occurs more rapidly. The Na+/K+ pump is a possible target of T3 action, involved in the pathogenesis of the anasarcatic condition observed in our COVID-19 patients with NTIS. Finally, measurement of BIA parameters may represent good endpoints to evaluate the benefit of future clinical interventional trials, based on the administration of T3 in patients with NTIS.

Euthyroid sick syndrome as an early surrogate marker of poor outcome in mild SARS-CoV-2 disease.

BACKGROUND: The new coronavirus 19 disease (COVID-19) represents the current worldwide emergency. According to past evidence, a simple biomarker, such as low free triiodothyronine (fT3) levels, within the framework of euthyroid sick syndrome (ESS), might help to identify patients with unfavourable outcomes. OBJECTIVE: Evaluation of ESS significance in hospitalized mild COVID-19 patients. DESIGN: Prospective study, from 1 April 2020 to 31 May 2021. PARTICIPANTS: COVID-19 patients with mild disease at hospital admission. MAIN MEASURES: At hospital admission, eligible patients underwent a complete thyroid function evaluation. Subjects with previous thyroid disease or with thyroid-interfering medications were excluded. Levels of fT3 were correlated to biochemical markers and to patient outcome, the latter considered as favourable in the event of infection recovery and unfavourable in the event of death or transfer to an intensive care unit (ICU). KEY RESULTS: Of 600 screened patients, 506 were eligible for this study. Of those, 94 (19%) died during hospitalization and 80 (18%) required a transfer to ICU. The most frequent thyroid disorder was ESS (57%). Admission levels of fT3 were significantly lower within the unfavourable outcome subgroup (p < 0.001) and were negatively associated with several poor prognostic markers, including IL-6 (p < 0.001). In Kaplan-Meier and Cox regression analyses, fT3 was independently associated with poor outcome and death (p = 0.005 and p = 0.037, respectively). A critical fT3 threshold for levels < 2.7 pmol/l (sensitivity 69%, specificity 61%) was associated with a 3.5-fold increased risk of negative outcome (95%CI 2.34-5.34). CONCLUSION: Low fT3 levels, in the framework of ESS, resulted as being a valid predictor of unfavourable outcomes in a very early stage population of COVID-19.

Possible Contributions of Nongenomic Actions of Thyroid Hormones to the Vasculopathic Complex of COVID-19 Infection.

BACKGROUND: Integrin αvß3 is a cell membrane structural protein whose extracellular domain contains a receptor for L-thyroxine (T4). The integrin is expressed in rapidly dividing cells and its internalization is prompted by T4. The protein binds viruses and we have raised the possibility elsewhere that action of free T4 (FT4)-when he latter is increased in the nonthyroidal illness syndrome (NTIS) known to complicate COVID-19 infecction-may enhance cellular uptke of SARS-CoV-2 and its receptor. OBJECTIVE: Because T4 also acts nongenomically via the integrin to promote platelet aggregation and angiogenesis, we suggest here that T4 may contribute to the coagulopathy and endothelial abnormalities that can develop in COVID-19 infections, particularly when the lung is primary affected. DISCUSSION AND CONCLUSIONS: Elevated FT4 has been described in the NTIS of COVID-19 patients and may be associated with increased illness severity, but the finding of FT4 elevation is inconsistent in the NTIS literature. Circulating 3,5',3'-triiodo-L-thyronine (reverse T3, rT3) are frequently elevated in NTIS. Thought to be biologically inactive, rT3in fact stimulates cancer cell proliferation via avb3 and also may increase actin polymerization. We propose here that rT3 in the NTIS complicating systemic COVIF-19 infection may support coagulation and disordered blood vessel formation via actin polymerization.

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.

Correlation between inflammatory parameters and pituitary-thyroid axis in patients with COVID-19.

PURPOSE: Inflammation plays a critical role in the progression of COVID-19. Nonthyroidal illness syndrome (NTIS) has been increasingly recognized in affected patients. We aim to evaluate the correlation of thyroid hormones with markers of inflammation and association with disease outcome in hospitalized patients with COVID-19, and in two profiles of NTIS (low T3-normal/low FT4 vs. low T3-high FT4). METHODS: consecutive patients admitted to a nonintensive care unit for COVID-19 were recruited. Infection was mild in 22%, moderate in 27.1% and severe in 50.8%; 7.41% died. T4, T3, FT4, FT3, and their ratios (T3/T4, FT3/FT4) were correlated with albumin, ferritin, fibrinogen, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer. RESULTS: Fifty five patients (50.9% men, median age 56 years) were included. Albumin correlated positively with T3 and hormones ratios, but negatively with FT4. T3, FT3, T3/T4, and FT3/FT4 correlated inversely with ferritin, fibrinogen, ESR, CRP, LDH, and D-dimer. FT4 showed direct correlation with fibrinogen and ESR. T3/T4 was lower in severe compared to mild/moderate disease [7.5 (4.5-15.5) vs. 9.2 (5.8-18.1); p = 0.04], and lower in patients who died than in those discharged [5 (4.53-5.6) vs. 8.1 (4.7-18.1); p = 0.03]. A low T3/high FT4 profile was associated with lower albumin, higher ferritin, and severity. CONCLUSION: In this cohort, thyroid hormones correlated with inflammation and outcome. T3 and T3/T4 correlated inversely with inflammatory markers; a low T3/T4 ratio was associated with severity and poor prognosis. Patients with low T3 but high FT4 had higher ferritin, lower albumin, and more severe disease at presentation.

Thyroid Hormone Profile and Its Prognostic Impact on the Coronavirus Disease 2019 in Korean Patients.

BACKGROUND: Data on the association between coronavirus disease 2019 (COVID-19) and thyroid have been reported, including overt thyrotoxicosis and suppression of thyroid function. We aimed to evaluate the thyroid hormone profile and its association with the prognosis of COVID-19 in Korean patients. METHODS: The clinical data of 119 patients with COVID-19, admitted in the Myongji Hospital, Goyang, South Korea, were retrospectively evaluated. The thyroid hormone profiles were analyzed and compared based on disease severity (non-severe disease vs. severe to critical disease). Clinical outcomes were analyzed according to the tertiles of thyroid hormones. RESULTS: Of the 119 patients, 76 (63.9%) were euthyroid, and none presented with overt thyroid dysfunction. Non-thyroidal illness syndrome was the most common manifestation (18.5%), followed by subclinical thyrotoxicosis (14.3%) among patients with thyroid dysfunction. Thyroid stimulating hormone (TSH) and triiodothyronine (T3) levels were significantly lower in patients with severe to critical disease than in those with non-severe disease (P<0.05). Patients in the lowest T3 tertile (<0.77 ng/mL) had higher rates of mechanical ventilation, intensive care unit admission, and death than those in the middle and highest (>1.00 ng/mL) T3 tertiles (P<0.05). COVID-19 patients in the lowest T3 tertile were independently associated with mortality (hazard ratio, 5.27; 95% confidence interval, 1.09 to 25.32; P=0.038) compared with those in the highest T3 tertile. CONCLUSION: Thyroid dysfunction is common in COVID-19 patients. Changes in serum TSH and T3 levels may be important markers of disease severity in COVID-19. Decreased T3 levels may have a prognostic significance in COVID-19 related outcome.

Low free-T3 serum levels and prognosis of COVID-19: systematic review and meta-analysis.

OBJECTIVES: There is increasing interest regarding the relationship between serum levels of free triiodothyronine (fT3) and outcomes of COronaVIrus Disease-19 (COVID-19) patients. As several recent reports have described a worse prognosis in patients with low fT3 levels, we performed a meta-analysis to assess the prognostic role of fT3 serum levels in patients with COVID-19 as this information could be clinically relevant for the management of these patients. METHODS: The methodology was registered in the International prospective register of systematic reviews (PROSPERO) database under the protocol number CRD42021260952. A systematic search was carried out on PubMed, Embase, Web of Science, and Scopus from May to June 2021 without time and language restrictions. The literature search strategy was based on the following keywords: (T3 OR fT3 OR triiodothyronine) AND (COVID-19) AND (prognosis OR survival). RESULTS: The literature search identified 163 studies. Seven retrospective studies met the inclusion and exclusion criteria and were included in the meta-analysis. The included studies had a total of 1,183 patients. From the analysis of the included studies, lower fT3 serum levels were consistently observed in intensive care unit (ICU) than in non-ICU patients and in non-survivors than survivors, respectively. CONCLUSIONS: Serum fT3 concentrations are significantly lower in patients with severe COVID-19 than in non-severely ill patients and predict all-cause mortality of patients with severe COVID-19. Accordingly, fT3 may become a simple tool for stratified management of patients with severe COVID-19.

Non-thyroidal illness syndrome and SARS-CoV-2-associated multisystem inflammatory syndrome in children.

PURPOSE: COVID-19 disease may result in a severe multisystem inflammatory syndrome in children (MIS-C), which in turn may alter thyroid function (TF). We assessed TF in MIS-C, evaluating its impact on disease severity. METHODS: We retrospectively considered children admitted with MIS-C to a single pediatric hospital in Milan (November 2019-January 2021). Non-thyroidal illness syndrome (NTIS) was defined as any abnormality in TF tests (FT3, FT4, TSH) in the presence of critical illness and absence of a pre-existing hormonal abnormality. We devised a disease severity score by combining severity scores for each organ involved. Glucose and lipid profiles were also considered. A principal component analysis (PCA) was performed, to characterize the mutual association patterns between TF and disease severity. RESULTS: Of 26 (19 M/7F) patients, median age 10.7 (IQR 5.8-13.3) years, 23 (88.4%) presented with NTIS. A low FT3 level was noted in 15/23 (65.3%), while the other subjects had varying combinations of hormone abnormalities (8/23, 34.7%). Mutually correlated variables related to organ damage and inflammation were represented in the first dimension (PC1) of the PCA. FT3, FT4 and total cholesterol were positively correlated and characterized the second axis (PC2). The third axis (PC3) was characterized by the association of triglycerides, TyG index and HDL cholesterol. TF appeared to be related to lipemic and peripheral insulin resistance profiles. A possible association between catabolic components and severity score was also noted. CONCLUSIONS: A low FT3 level is common among MIS-C. TF may be useful to define the impact of MIS-C on children's health and help delineate long term follow-up management and prognosis.