Neuroimmunoendocrinology of SARS-CoV 2 Infection

Abstract

This review is aimed at illustrating and discussing the neuroimmune endocrinological aspects of the SARS-CoV-2 infection in light of the studies on this topic that have so far appeared in the literature. The most characteristic findings and pending controversies were derived by PubMed and Scopus databases. We included original and observational studies, reviews, meta-analysis, and case reports. The entry of the coronavirus into susceptible cells is allowed by the interaction with an ecto-enzyme located on human cells, the angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 also targets the central nervous system (CNS), including hypothalamic-pituitary structures, as their tissues express ACE2, and ACE2 mRNA expression in hypothalamus and pituitary gland cells has been confirmed in an autoptic study on patients who died of COVID 19. SARS-CoV-2 infection may cause central endocrine disorders in acute phase and in post-COVID period, particularly due to the effects of this virus at CNS level involving the hypothalamic-pituitary axis. The aggression to the hypothalamus-pituitary region may also elicit an autoimmune process involving this axis, responsible consequently for functional disorders of the satellite glands. Adrenal, thyroid and gonadal dysfunctions, as well as pituitary alterations involving GH and prolactin secretions, have so far been reported. However, the extent to which COVID-19 contributes to short- and long-term effects of infection to the endocrine system is currently being discussed and deserves further detailed research.

Keywords: ACTH; COVID-19; cortisol; hypothalamus; pituitary autoimmunity; pituitary gland.

Figure 1

Possible strategy by which SARS-CoV-2 may deflect the host’s immune response. The amino-acid sequence, which the virus shares with the ACTH, induces the production of autoantibodies against this pituitary hormone that prevents the suitable adrenal response to the stress. ACTH: adrenocorticotropic hormone; AVP: arginine-vasopressin; IL-1β: interleukin 1 beta; IL-6: interlukin 6; TNF-α: Tumor Necrosis Factor α; +: increase; −: negative effect; ↑: Increase.