key: cord-1018558-bcfxhhrl
authors: Cagnacci, Angelo; Xholli, Anjeza
title: Age-related difference in the rate of COVID-19 mortality in women versus men
date: 2020-05-24
journal: Am J Obstet Gynecol
DOI: 10.1016/j.ajog.2020.05.039
sha: c220991f80fcbdec7ddee6d595962309950dde00
doc_id: 1018558
cord_uid: bcfxhhrl

nan

Mortality by COVID-19 is lower in women than in men. 1 Mortality pertains mostly to older ages, 17

where a protective effect of ovarian hormones is difficult to envision. Yet speculation on a possible 18 protective effect of estrogens are being formulated. So far, the epidemiological evidence has not 19 clarified whether mortality of infected individuals changes differently between sexes with age. This 20 infection was obtained, stratified by age and sex, from the ISTAT database in the year 2018. 3 The 30 data of the entire year were adapted to a period of 2 months. This death rate was subtracted from 31 that observed in the cohort of COVID-19 infected individuals, to obtain the estimated excess death 32 rate due to COVID-19. Excess death rate was then stratified by sex and age in categories of 10 33 years. In order to evaluate whether the difference of excess death rate (death/infected) due to 34 COVID-19 between men and women remained constant across age, for any age category, the ratio 35 of death rate of women/death rate of men was calculated and expressed as a percentage. 36 37

In the ISS report there were 147706 affected individuals of whom 17520 died during the 2 months 39 (death rate of 11.8%). Death rate of non-infected individuals for a similar period was 1.00%. 40

Accordingly, excess death rate due to COVID-19 was estimated to be 10.8%. Excess death rate 41 increased with age and was always lower in women than in men ( Figure 1A) . In women, an excess 42 death rate by COVID-19 higher than 1% was observed after 50-59 years of age, while in men after 43 30-39 years of age ( Figure 1A) . The difference in excess death rate by COVID-19 between women 44 and men changed with age. By considering men's death rate equal to 100%, women's death rate 45 was 27.8% of this (-72.2%) in ages 20 to 59 years, and 50.6% of this (-49.4%) in ages 60 to 89 46 years ( Figure 1B) . 47 48

Excess death rate by COVID-19 is lower in women than in men. Lifestyle, rate of smoking or other 50 risk factors may be different between men and women. Unfortunately, these data were not 51 available, and we could not control for them. Nevertheless, we controlled for natural mortality, that 52 should integrate differences in risk factors between the two sexes. Genes are also different between 53 males and females. All these factors may explain the different rate of COVID-19 related mortality 54 between sexes but are unlikely to explain the reason why the difference of death rate between sexes 55 changed abruptly and constantly after 50-59 years of age. The endocrine milieu is different between 56 men and women. In women, ovarian hormones influence inflammation, immunity and also the 57 expression of ACE2 converting enzyme 4 that seems to play a role in determining COVID-19 58 disease progression. 1 These effects are lost after the menopause, that in Italian women occurs at 59 median age of 50 years (range 30-61 years). 5 Unfortunately, we could not perform a more specific 60 calculation by dividing women before and after the menopause, but present results may prompt 61 further analyses on this issue. 

Organ-protective effect of angiotensin-converting enzyme 2 and 64 its effect on the prognosis of COVID-19

it/tvm2018/index.php?lingua=ita (Accessed on

Protective regulation of the ACE2/ACE gene expression 69 by estrogen in human atrial tissue from elderly men

Season of birth 73 influences the timing of menopause