A Literature Review on SARS-CoV-2 and Other Viruses in Thyroid Disorders: Environmental Triggers or No-Guilty Bystanders?

A growing number of findings indicate a relationship between COVID-19 infection and thyroid dysfunction. This association is also strengthened by knowledge on the potential of viral infections to trigger thyroid disorders, although the exact underlying pathogenetic process remains to be elucidated. This review aimed to describe the available data regarding the possible role of infectious agents, and in particular of SARS-CoV-2, in the development of thyroid disorders, summarizing the proposed mechanisms and levels of evidence (epidemiological, serological or direct presence of the viruses in the thyroid gland) by which the infection could be responsible for thyroid abnormalities/diseases. Novel data on the association and mechanisms involved between SARS-CoV-2 vaccines and thyroid diseases are also discussed. While demonstrating a clear causal link is challenging, numerous clues at molecular and cellular levels and the large amount of epidemiological data suggest the existence of this relationship. Further studies should be taken to further investigate the true nature and strength of this association, to help in planning future preventive and therapeutic strategies for more personal and targeted care with attention to the underlying causes of thyroid dysfunction.

The Expression Levels of SARS-CoV-2 Infection-Mediating Molecules Promoted by Interferon-γ and Tumor Necrosis Factor-α Are Downregulated by Hydrogen Sulfide.

Autoimmune thyroid diseases (AITDs), which include Hashimoto's thyroiditis (HT) and Graves' disease (GD), have a higher prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the literature. The effects of AITD-associated cytokines on SARS-CoV-2 infection-mediating molecule levels might be involved in the pathogenesis of susceptibility. We speculated that hydrogen sulfide (H2S) might attenuate this process since H2S has antiviral effects. Using immunohistochemistry, we found that angiotensin-converting enzyme-II (ACE2) expression was higher in the HT group and neuropilin 1 (NRP1) expression was higher in HT and GD groups than in the normal group, while transmembrane protease serine type 2 (TMPRSS2) expression was lower in HT and GD groups. When culturing primary thyrocytes with cytokines or sodium hydrosulfide (NaHS) plus cytokines, we found that ACE2 and NRP1 mRNA levels were upregulated while TMPRSS2 levels were downregulated by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). After pretreatment with NaHS in thyrocytes, ACE2 and NRP1 expression were downregulated compared to IFN-γ or TNF-α treatment, and NaHS had no effect on TMPRSS2 expression. Our findings suggested that IFN-γ and TNF-α, which are elevated in AITDs, promoted ACE2 and NRP1 expression and inhibited TMPRSS2 expression. H2S might protect against SARS-CoV-2 infection by downregulating ACE2 and NRP1 levels.

Graves' Disease Following SARS-CoV-2 Vaccination: A Systematic Review.

(1) Background: Autoimmune diseases, including autoimmune endocrine diseases (AIED), are thought to develop following environmental exposure in patients with genetic predisposition. The vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could represent a new environmental trigger for AIED, including Graves' disease (GD). (2) Methods: We performed a literature search of MEDLINE/PubMed databases regarding thyroid dysfunction after SARS-CoV-2 vaccination since 1 January 2020 to 31 July 2022, considering only cases of thyrotoxicosis that meet the 2016 American Thyroid Association guidelines criteria for the diagnosis of GD and arising after administration of the anti-SARS-CoV-2 vaccine, regardless of the number of doses. (3) Results: A total of 27 articles were identified, consisting of case reports or case series, of which 24 describe the appearance of 48 new diagnoses of GD and 12 GD recurrences arising after the administration of the anti-SARS-CoV-2 vaccine, and 3 papers that instead report only 3 cases of GD relapse following vaccination. (4) Conclusions: physicians should be aware of the possibility of developing GD and other autoimmune sequelae following SARS-CoV-2 vaccination. Regardless of the underlying pathogenetic mechanisms (autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome), cytokines induction, molecular mimicry, and cross-reactivity), an individual predisposition seems to be decisive for their development.

Thyroid autoimmunity and SARS-CoV-2 infection: Report of a large Italian series.

Since the beginning of the pandemic, numerous risk factors have been associated with SARS-CoV-2 infection and COVID-19 outcomes, such as older age, male sex, and the presence of comorbidities, such as hypertension, obesity, and diabetes. Preliminary data also suggest epidemiological association between SARS-CoV-2 infection and systemic autoimmune disease. For this reason, we investigated if patients affected by autoimmune thyroid disorders (AITD) are at risk of developing SARS-CoV-2 infection or COVID-19 disease. From April to September 2020, we have conducted a telephone survey that included 515 consecutive unselected patients with known thyroid disorders, of which 350 were affected by AITD. All 11 definitive diagnosis of COVID-19 (def-sympt-COVID-19) belonged to the AITD group, while the rest 14 cases highly suspected for COVID-19 (suspect-sympt-COVID-19) were equally detected in both group (7 in AITD and 7 in not-AITD). The overall prevalence of symptomatic COVID-19 (def-sympt-COVID-19 + suspect-sympt-COVID-19), recorded in the 350 AITD population was statistically significant higher compared to that reported in the Italian and Tuscan general population at the same time period of the present survey (18/350 = 5.14% vs 516/100000 = 0.51% [p < 0.001; OR = 10.45, 95% CI 6.45-16.92] and vs 394/100000 = 0.39% [p < 0.001; OR = 13.70, 95% CI 8.44-22.25], respectively). Therefore, our results suggest a higher prevalence of SARS-CoV-2 infection and COVID-19 disease in patients with AITD.