Relationship between betacoronaviruses and the endocrine system: a new key to understand the COVID-19 pandemic—A comprehensive review

Abstract

Background A new harmful respiratory disease, called COVID-19 emerged in China in December 2019 due to the infection of a novel coronavirus, called SARS-Coronavirus 2 (SARS-CoV-2), which belongs to the betacoronavirus genus, including SARS-CoV-1 and MERS-CoV. SARS-CoV-2 shares almost 80% of the genome with SARS-CoV-1 and 50% with MERS-CoV. Moreover, SARS-CoV-2 proteins share a high degree of homology (approximately 95%) with SARS-CoV-1 proteins. Hence, the mechanisms of SARS-Cov-1 and SARS-Cov-2 infection are similar and occur via binding to ACE2 protein, which is widely distributed in the human body, with a predominant expression in endocrine tissues including testis, thyroid, adrenal and pituitary. Purpose On the basis of expression pattern of the ACE2 protein among different tissues, similarity between SARS-Cov-1 and SARS-Cov-2 and the pathophysiology of COVID-19 disease, we aimed at discussing, after almost one-year pandemic, about the relationships between COVID-19 infection and the endocrine system. First, we discussed the potential effect of hormones on the susceptibility to COVID-19 infection; second, we examined the evidences regarding the effect of COVID-19 on the endocrine system. When data were available, a comparative discussion between SARS and COVID-19 effects was also performed. Methods A comprehensive literature search within Pubmed was performed. This review has been conducted according to the PRISMA statements. Results Among 450, 100 articles were selected. Tissue and vascular damages have been shown on thyroid, adrenal, testis and pituitary glands, with multiple alterations of endocrine function. Conclusion Hormones may affect patient susceptibility to COVID-19 infection but evidences regarding therapeutic implication of these findings are still missing. SARS and COVID-19 may affect endocrine glands and their dense vascularization, impairing endocrine system function. A possible damage of endocrine system in COVID-19 patients should be investigated in both COVID-19 acute phase and recovery to identify both early and late endocrine complications that may be important for patient’s prognosis and well-being after COVID-19 infection.

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

“…As shown, the circles of correlation confirm the results displayed in Fig. 1, in which variables FT3, FT4 and total cholesterol are dependent on the presence of Dim2, those related to organ damage and inflammation are dependent on the presence Dim1 and the variables TyG index and triglycerides are dependent on the Dim3 T3 syndrome, which is considered a useful adaptation to preserve energy during critical illness [24][25][26][28][29][30]. As in our children, patients with critical illness experience a concomitant weight loss due to a hypercatabolic state [33].…”

“…Acute and chronic Illnesses may induce profound modulations and interactions in a number of neuroendocrine systems including changes within the HPT axis [24][25][26]. Data in the literature suggest that SARS-CoV-2 may also have an impact on thyroid tissue and function [16,25,27].…”

“…A second potential explanation is systemic immune activation in response to SARS-CoV-2 infection may cause thyroid damage. A third hypothesis is a selective transient pituitary dysregulation, due to both the direct cytotoxic effect of the virus at the pituitary level and an indirect effect via the activation of proinflammatory cytokines, which produce a "cytokine storm" that would, in turn, induce NTIS [24][25][26][28][29][30].…”

Thyroid sequelae of COVID-19: a systematic review of reviews

“…Piticchio [18] To discuss the relationship between COVID-19 infection and the endocrine glands and compare it with SARS-CoV A possible damage of endocrine system in COVID-19 patients should be investigated in both COVID-19 acute phase and recovery to identify both early and late endocrine complications that may be important for patient's prognosis and well-being after infection it is known that patients in the intensive care unit typically present with decreased tri-iodothyronine, low thyroxine, and normal range or slightly decreased TSH (i.e., non-thyroidal illness syndrome or low-T3 syndrome), even if no proof exists for causality of this association [27]. Furthermore, it is known that thyroid hormones levels can hold a role to predict a worse prognosis in these patients [27].…”

“…By the search strategy, a number of 247 records was initially found. Among these, according to the above criteria, 238 studies were excluded since they were not review articles, and nine reviews were finally included [7,[11][12][13][14][15][16][17][18] (Fig. 1).…”