Gender susceptibility to COVID-19: a review of the putative role of sex hormones and X chromosome.
J Endocrinol Invest
; 44(5): 951-956, 2021 May.
Article
in English
| MEDLINE | ID: covidwho-763952
ABSTRACT
BACKGROUND:
The recent emergence of COVID-19 poses a global health emergency. One of the most frequently reported data is sex-related severity and mortality according to the last available analysis on 239,709 patients in Italy, lethality is 17.7% in men and 10.8% in women, with 59% of total deaths being men. Interestingly, the infection rate is lower in males than in females, with 45.8% and 54.2% of positive cases, respectively, suggesting that gender-related factor may worsen disease evolution. A tentative hypothesis to explain these findings is the role of angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 involved in viral infection.PURPOSE:
In this review, we summarize the available evidence pointing to gender-related differences in ACE2 and TMPRSS2 expression, from both genetic and endocrine points of view.RESULTS:
Altogether, available evidence points toward two not-mutually exclusive mechanisms in gender susceptibility to COVID-19 by sex hormonal regulation of ACE2 and TMPRSS2. On one hand, ACE2 expression could be increased in women, either by estrogens or constitutively by X chromosome inactivation escape or by reduced methylation, providing a larger reservoir of ACE2 to maintain the fundamental equilibrium of RAS regulatory axis. On the other, low levels of androgens in women may keep at low levels TMPRSS2 expression, representing a further protective factor for the development of COVID-19 infection, despite the increased expression of ACE2, which represents the Trojan horse for SARS-CoV-2 entry.CONCLUSIONS:
Both mechanisms consistently point to the role of sex hormones and sex chromosomes in the differential severity and lethality of COVID-19 in men and women.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Gonadal Steroid Hormones
/
Genetic Predisposition to Disease
/
Chromosomes, Human, X
/
COVID-19
Type of study:
Etiology study
/
Observational study
/
Prognostic study
Limits:
Female
/
Humans
/
Male
Language:
English
Journal:
J Endocrinol Invest
Year:
2021
Document Type:
Article
Affiliation country:
S40618-020-01383-6
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