Two Cases of Severe Autoimmune Thyrotoxicosis Following SARS-CoV-2 Infection

Abstract

Since the start of the COVID-19 pandemic, there have been multiple reports of related thyroid dysfunction, most commonly, thyroiditis. The exact mechanism for this has not been elucidated, but it is known that thyroid gland cells have both angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) receptors, which the SARS-CoV-2 virus uses to enter cells. While SARS-CoV-2 has also been shown to precipitate other autoimmune diseases, there are only a few reported cases of new onset Graves’ disease in the setting of SARS-CoV-2 infection. We report 2 patients who presented with severe thyrotoxicosis (thyroid storm and impending storm) that was likely precipitated by SARS-CoV-2 infection. Both patients had no previous history of hyperthyroidism, and potentially also developed Graves’ disease after getting COVID-19. The addition of these cases to the medical literature will further highlight the fact that SARS-CoV-2 infection should be considered a causative agent for thyrotoxicosis when no other cause can be found, and that SARS-CoV-2 may be a potential trigger for autoimmune thyroid disease. It is important to know the SARS-CoV-2 status of such patients for infection control purposes, and to identify patients who may have their hospital course complicated by this disease. These cases may also help further our understanding of the etiology of autoimmune thyroid disease following a viral infection.

SARS-CoV-2 triggered relapse of multiple sclerosis

“…A fourth argument is that retrospective observational studies have shown that the risk of exacerbation of MS has increased during the pandemic [6] . A fifth argument is that SARS-CoV-2 was made responsible for a number of newly onset or flares of immunological disease: Immunologic disorders in addition to MS reported having been triggered by a SARS-CoV-2 infection include myasthenia, NMO-SD, immune hepatitis, myositis, myocarditis, vestibular neuritis, Graves disease, immune thrombocytopenia, rheumatoid arthritis, Sjögren syndrome, juvenile idiopathic arthritis, and autoimmune thyroiditis [10] , [11] , [12] . A sixth argument is that SARS-CoV-2 triggers a hyper-inflammatory immune reaction, which can be documented by lymphopenia, elevated cytokines, chemokines, and glial markers (cytokine storm) occasionally leading to pulmonary failure, ARDS, and death [13] .…”

COVID-19 and thyroid disease: clinical course and prognosis

“…In turn, referring to the presence of TD in patients with COVID-19, in addition to the possibility of dysfunction is likely dysfunction of the hypothalamic-pituitary-adrenal axis [31]. It has also been shown that SARS-CoV-2 provokes autoimmune diseases [9,42].…”

“…The identified affinity of SARS-CoV-2 for the thyroid gland draws attention to the potential risk of developing GD [9,45] and Hashimoto's thyroiditis [26], but SAT -inflammatory thyroid disease of viral or postviral origin [24,29,[45][46][47] was the most common thyroiditis associated with COVID-19 [2,9,48]. Previous viral infection, which occurred approximately 2-6 weeks earlier, is considered a factor that provokes SAT [1,44,46].…”

“…Published clinical cases of 2 patients without a history of TD who developed severe TT of varying severity ("cytokine storm" and "impending cytokine storm"), possibly caused by SARS-CoV-2 infection and suggested SARS-CoV infection-2 as a causative agent of TT in the case when no other cause could be found [9].…”

“…Key factors in SARS-CoV-2 infection are angiotensin-converting enzyme 2 (ACE2), which serves as a "receptor" that allows the virus to enter thyroid cells, and the transmembrane protease that SARS-CoV-2 virus uses to penetrate cells [9,10]. In addition, ACE2, the SARS-CoV-2 receptor, is expressed on myocytes and vascular endothelial cells, so there is at least a theoretical potential for direct virus damage to the heart [8].Elderly age, male gender and comorbidities are the main risk factors for more severe COVID-19 and worse treatment outcomes [8,11,12].…”