ACE2 expression and sex disparity in COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) death rate differs depending on sex: in Chinese confirmed cases, while the infection rate among men and women is similar, the death rate among men is 4.7% compared with 2.8% for women 1. Italian data are similar as the reported death rate in men is significantly higher than that in women, 16.6% vs. 9.1%, respectively. Moreover, preliminary data from Italian epidemics suggest also a significant sex difference in infection rate, being 52.5% in women and 47.5% in men (Integrated Surveillance on COVID19 epidemic in Italy published by Italian Institute of Health, April 28th 2020, https://www.epicentro.iss.it/coronavirus/bollettino/ Bollettino-sorveglianza-integrata-COVID-19_28-aprile_2020.pdf). So far, the mechanisms underlying the observed gender bias are not disclosed; however, some hypotheses can be put forward on the basis of current knowledge on gender differences in respiratory viral diseases.

Renin Angiotensin System, COVID-19 and Male Fertility: Any Risk for Conceiving?

“…Concerns about male fertility started to arise when epidemiologic studies on the gender distribution observed that male patients are more affected and with increased severity by SARS-CoV-2 infection. The hormone-regulated expression of ACE2 and other RAS receptors seems to be the main reason for this discrepancy [ 32 ].…”

“…On the other hand, the TMPRSS2 concentration is higher in men than women, through an androgen-dependent gene expression [ 30 ]. Moreover, since in vitro studies demonstrated that estrogens can overrule oxidative and inflammatory stress, it has been hypothesized that the upregulation of ACE2 in women could also be protective against tissue damage [ 31 , 32 ].…”

Vitamin D and Sex Differences in COVID-19

“…In particular, ACE2 is encoded on X-chromosome, in sites commonly escaping the inactivation of one X-chromosome in mammalian XX cells (XCI), and could therefore be overexpressed in women (19). Moreover, estrogen induces an increase of ACE2 expression that, as reported above, could play a protective role in acute respiratory distress (11,20), whereas androgen can increase the expression and activation of transmembrane serine-protease 2, (TMPRSS2), that facilitates virus-cell membrane fusion, thus favoring the infection (21).…”

Pola Penyebaran Infeksi Covid-19 di Provinsi Papua Tahun 2020

“…Jumlah dan aktivitas sel imun alamiah termasuk monosit, makrofage dan sel dendritik serta respon imun inflamasi secara umum lebih tinggi di perempuan dari pada laki-laki (Gebhard et al, 2020). Perbedaan Jenis kelamin menyebabkan perbedaan gaya hidup, seperti kecanduan merokok yang lazim pada pria dari pada wanita, dianggap salah satu faktor risiko potensial untuk menjadi pneumonia akibat CoViD-19 (Gagliardi et al, 2020). Merokok dapat meningkatkan ekspresi gen ACE2, protein yang mengikat SARS-CoV-2 yang dapat meningkatkan terjadinya infeksi CoViD-19.…”