SARS-CoV-2 Can Disrupt Endocrine System Via ACE2

By Reuters Staff

July 24, 2020

NEW YORK (Reuters Health) - SARS-CoV-2, the coronavirus that causes COVID-19, can disrupt various endocrine functions through its effects on the angiotensin converting enzyme 2 (ACE2), its entry point into cells, researchers say.

Dr. Eric Lazartigues from Louisiana State University Health Sciences Center and Southeast Louisiana Veterans Health Care Systems, New Orleans, and colleagues summarize ACE2 expression and function in endocrine tissues and the possible impact of SARS coronaviruses in endocrinology in their online review in Endocrinology.

SARS-CoV-2 entry into cells relies on binding to ACE2 followed by priming of the viral spike protein, mainly by the serine protease TMPRSS2, which is encoded by an androgen-related gene expressed predominantly in the prostate and at lower levels in the lung, colon, liver, kidneys, and pancreas.

ACE2 protein expression has been reported in the mouse brain (in hypothalamic regions associated with food intake and metabolic regulation), in glucagon-producing alpha-cells of mouse and human pancreatic islets, in mouse adipose tissue, and in Leydig and Sertoli cells of the human testis.

SARS-CoV-2 infection has been associated with pancreatic islet dysfunction, including pancreatic injury and mostly reversible new-onset diabetes.

Testicular involvement with orchitis has been reported in a few patients, but the absence of SARS-CoV-2 in autopsy specimens of the testes argue for an immune-mediated orchitis rather than a direct effect of the virus. Significant increases in serum luteinizing hormone (LH) and decreases in the serum ratio of testosterone:LH have also been reported.

In the earlier SARS epidemic in Singapore, hypothalamic-pituitary-adrenal axis dysfunction occurred transiently in 39% of patients, and several autopsy specimens revealed evidence of primary injury to the thyroid gland.

"With respect to COVID-19, clinical studies show more severe outcomes in patients with diabetes, obesity, and hypertension," the authors conclude. "However, the lack of data in humans on ACE2 expression in pathological conditions in endocrine tissues does not allow us to conclude on a direct role of ACE2 expression in severe COVID-19 outcomes."

"Data are needed in patients to determine whether these comorbidities are associated with enhanced or reduced expression of ACE2, or TMPRSS2, that could affect SARS-CoV-2 infection," they add.

Dr. Lazartigues did not respond to a request for comments.

SOURCE: Endocrinology, online July 11, 2020.