Activation of Type I and Type II Interferon Signaling in SARS-CoV-2-Positive Thyroid Tissue of Patients Dying from COVID-19.

Background: Thyroid dysfunctions have been reported after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, the biological mechanisms behind these conditions remain unexplored. Herein, we report on changes of the immune transcriptome in autoptic thyroid tissues of people who have died from coronavirus disease 2019 (COVID-19). Methods: Twenty-five autoptic thyroid specimens of subjects dying from COVID-19 were investigated. Eleven autoptic thyroid specimens of subjects dying from causes other than infectious conditions served as controls. RNA transcripts of 770 immune-related genes together with RNA genomes of multiple coronavirus types were measured by the nCounter system. Reverse transcription-polymerase chain reaction for two SARS-CoV-2 genes was used to assess virus positivity. Results were validated by immunohistochemistry. Results: The SARS-CoV-2 genome and antigens were detected in 9 of 25 (36%) thyroid specimens from the COVID-19 cohort. Virus-negative thyroid tissues from COVID-19 subject did not show changes of gene transcription nor significant numbers of infiltrating immune cells. Conversely, SARS-CoV-2-positive thyroid specimens showed marked upregulation of immune genes, especially those proper of the type I and type II interferon (IFN) pathways. In infected tissues, infiltrates of innate immune cells (macrophages and polymorphonuclear neutrophils) were prevalent. Conclusions: The thyroid gland can be directly infected by the SARS-CoV-2. Infection strongly activates IFN pathways. The direct viral insult combined with an intense immune response may trigger or worsen thyroid conditions in predisposed individuals.

Association of hypothyroidism with acute COVID-19: a systematic review.

OBJECTIVE: There is an increasing body of literature on the impact of COVID-19 on the pituitary-thyroid axis. Therefore, we conducted a systematic review to assess the prevalence of hypothyroidism in patients with COVID-19. METHODS: A literature review was conducted using LitCOVID for study selection in PubMed and MEDLINE till May 2021. All relevant original articles evaluating thyroid dysfunction were included and information regarding the prevalence of hypothyroid disease in COVID-19 was retrieved from the eligible articles. RESULTS: Out of 32 articles, six articles qualified for the final analysis which included 1160 patients. There was significant heterogeneity among the included articles. Most of the patients had lower mean triiodothyronine (T3) and normal or low thyroid-stimulating hormone (TSH). Increased TSH ranged from 5.1% to 8% while low T3 was present in up to 28% of the patients. In these studies, the prevalence of altered thyroid hormones was significantly more in COVID-19 patients as compared to control groups. A positive correlation between low mean T3 and clinical severity of COVID-19 was reported. CONCLUSION: This systematic review reveals a significant proportion of hypothyroidism associated with COVID-19. Therefore, routine assessment of thyroid function is warranted in hospitalized COVID-19 patients.

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.

Coronavirus Disease 2019 and the Thyroid - Progress and Perspectives.

SARS-CoV-2 infection (COVID-19) is currently a tremendous global health problem. COVID-19 causes considerable damage to a wide range of vital organs most prominently the respiratory system. Recently, clinical evidence for thyroidal insults during and after COVID-19 has been accumulated. As of today, almost all non-neoplastic thyroid diseases, i.e., Graves' disease, Hashimoto's thyroiditis, subacute, painless and postpartum thyroiditis, have been reported as a complication of COVID-19, and causality by the virus has been strongly implicated in all of them. Similar thyroid problems have been reported in the past with the SARS-CoV outbreak in 2002. In this review, we briefly look back at the reported evidence of alteration in thyroid functionality and thyroid diseases associated with SARS-CoV and then proceed to examine the issue with COVID-19 in detail, which is then followed by an in-depth discussion regarding a pathogenetic link between Coronavirus infection and thyroid disease.

COVID-19 autopsy cases: detection of virus in endocrine tissues.

PURPOSE: The SARS-CoV-2 genome has been detected in a variety of human samples including blood, urine, semen, and faeces. However, evidence of virus presence in tissues other than lung are limited. METHODS: We investigated whether SARS-CoV-2 could be detected in 50 autoptic specimens of endocrine organs from 29 patients who died of COVID-19. RESULTS: The virus was detected in 25 specimens including ten abdominal subcutaneous adipose tissue samples (62%), six testes (67%), and nine thyroid (36%) samples. The analysis of multiple endocrine organ samples obtained from the same patients showed that, in virus-positive cases, the viral genome was consistently detected in all but two matched specimens. CONCLUSION: Our findings show that the virus spread into endocrine organs is a common event in severe cases. Further studies should assess the rate of the phenomenon in clinically mild cases. The potential long-term effects of COVID-19 on endocrine functions should be taken into consideration.

Potential Interaction Between SARS-CoV-2 and Thyroid: A Review.

The novel coronavirus disease 2019 (COVID-19) produced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sweeping the world in a very short time. Although much has been learned about the clinical course, prognostic inflammatory markers, and disease complications of COVID-19, the potential interaction between SARS-CoV-2 and the thyroid is poorly understood. In contrast to SARS-CoV-1, limited available evidence indicates there is no pathological evidence of thyroid injury caused by SARS-CoV-2. However, subacute thyroiditis caused by SARS-CoV-2 has been reported for the first time. Thyroid dysfunction is common in patients with COVID-19 infection. By contrast, certain thyroid diseases may have a negative impact on the prevention and control of COVID-19. In addition, some anti-COVID-19 agents may cause thyroid injury or affect its metabolism. COVID-19 and thyroid disease may mutually aggravate the disease burden. Patients with SARS-CoV-2 infection should not ignore the effect on thyroid function, especially when there are obvious related symptoms. In addition, patients with thyroid diseases should follow specific management principles during the epidemic period.

Thyroid Function Analysis in 50 Patients with COVID-19: A Retrospective Study.

Background: Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, it has affected >200 countries, areas, or territories in 6 continents. At present, whether COVID-19 has an effect on thyroid function is unclear. The aim of this study was to evaluate thyroid function in patients with COVID-19. Methods: Clinical manifestations, laboratory results, and chest computed tomography scans were retrospectively reviewed for 50 patients with laboratory-confirmed COVID-19 without a history of thyroid disease who underwent thyroid function testing during their course of COVID-19 infection and after recovery. They were admitted to the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, between January and March 2020. Healthy participants who underwent routine physical checkups and non-COVID-19 pneumonia patients with a similar degree of severity during the same period were included in the study as the control group. Thyroid hormone and thyrotropin (TSH) levels were analyzed and compared between the COVID-19 and control groups. Results: TSH lower than the normal range was present in 56% (28/50) of the patients with COVID-19. The levels of TSH and serum total triiodothyronine (TT3) of the patients with COVID-19 were significantly lower than those of the healthy control group and non-COVID-19 pneumonia patients. The more severe the COVID-19, the lower the TSH and TT3 levels were, with statistical significance (p < 0.001). The degree of the decreases in TSH and TT3 levels was positively correlated with the severity of the disease. The total thyroxine (TT4) level of the patients with COVID-19 was not significantly different from the control group. All the patients did not receive thyroid hormone replacement therapy. After recovery, no significant differences in TSH, TT3, TT4, free triiodothyronine (fT3), and free thyroxine (fT4) levels were found between the COVID-19 and control groups. Conclusions: The changes in serum TSH and TT3 levels may be important manifestations of the courses of COVID-19.

Thyrotoxicosis in patients with COVID-19: the THYRCOV study.

OBJECTIVE: This study assessed thyroid function in patients affected by the coronavirus disease-19 (COVID-19), based on the hypothesis that the cytokine storm associated with COVID-19 may influence thyroid function and/or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may directly act on thyroid cells, such as previously demonstrated for SARS-CoV-1 infection. DESIGN AND METHODS: This single-center study was retrospective and consisted in evaluating thyroid function tests and serum interleukin-6 (IL-6) values in 287 consecutive patients (193 males, median age: 66 years, range: 27-92) hospitalized for COVID-19 in non-intensive care units. RESULTS: Fifty-eight patients (20.2%) were found with thyrotoxicosis (overt in 31 cases), 15 (5.2%) with hypothyroidism (overt in only 2 cases), and 214 (74.6%) with normal thyroid function. Serum thyrotropin (TSH) values were inversely correlated with age of patients (rho -0.27; P < 0.001) and IL-6 (rho -0.41; P < 0.001). In the multivariate analysis, thyrotoxicosis resulted to be significantly associated with higher IL-6 (odds ratio: 3.25, 95% confidence interval: 1.97-5.36; P < 0.001), whereas the association with age of patients was lost (P = 0.09). CONCLUSIONS: This study provides first evidence that COVID-19 may be associated with high risk of thyrotoxicosis in relationship with systemic immune activation induced by the SARS-CoV-2 infection.

Characteristics of laboratory indexes in COVID-19 patients with non-severe symptoms in Hefei City, China: diagnostic value in organ injuries.

This study compared the laboratory indexes in 40 non-severe COVID-19 patients with those in 57 healthy controls. In the peripheral blood system of non-severe symptom COVID-19 patients, lymphocytes, eosinophils, basophils, total procollagen type 1 amino-terminal propeptide, osteocalcin N-terminal, thyroid-stimulating hormone, growth hormone, and insulin-like growth factor-binding protein 3 significantly decreased, and total protein, albumin, alanine transaminase, alkaline phosphatase, γ-glutamyl transferase, activated partial thromboplastin time, prothrombin time, fibrinogen, D-dimer, fibrinogen degradation products, human epididymal protein 4, serum ferritin, and C-reactive protein were elevated. SARS-CoV-2 infection can affect hematopoiesis, hemostasis, coagulation, fibrinolysis, bone metabolism, thyroid, parathyroid glands, the liver, and the reproductive system.