Sensitive to Infection but Strong in Defense—Female Sex and the Power of Oestradiol in the COVID-19 Pandemic

Abstract

The incidence of SARS-CoV2 infections is around 15% higher in premenopausal women compared to age matched men, yet the fatality rate from COVID-19 is significantly higher in men than women for all age strata. Sex differences have also been observed in recent epidemics including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), with SARS-CoV 2 virus infection sex differences appear more dramatic. The regulation and expression of the angiotensin converting enzyme 2 (ACE2) is the key for this special coronavirus SARS-CoV-2 to enter the cell. 17β-oestradiol increases expression level and activity of angiotensin converting enzyme-2 (ACE2) and the alternative signaling pathway of Ang II via the angiotensin II receptor type II (AT2R) and the Mas receptor is more dominant in female sex than in male sex. Maybe a hint to explain the higher infection risk in women. The same hormonal milieu plays a major role in protecting women where morbidity and mortality are concerned, since the dominant female hormone, oestradiol, has immune-modulatory properties that are likely to be protective against virus infections. It is also known that the X chromosome contains the largest number of immune-related genes, potentially conferring an advantage to women in efficient immune responsiveness. Lifestyle factors are also likely to be contributory. Premenopausal women could possibly face higher exposure to infection (hence higher infection rates) because economic conditions are often less favorable for them with less opportunity for home office work because of jobs requiring mandatory attendance. Due to the additional task of childcare, it is likely that contact times with other people will be longer. Women generally make healthier lifestyle choices, thus reducing the disease burden that confers high risk of mortality in COVID-19 infected men. This narrative review aims to present key concepts and knowledge gaps on the effects of oestrogen associated with SARS-CoV2 infection and COVID-19 disease.

Cutaneous adverse reactions of COVID ‐19 vaccines: A systematic review

“…In addition, the healthcare workforce is more likely to be visited by physicians 8,30 . Another justification is that females are sensitive to health situations and skin problems 38 . However, there is no definite identified reason for this issue and requires to be addressed in forthcoming studies.…”

The COVID-19 pandemic and the menstrual cycle: research gaps and opportunities

“…Depending on the type of contraceptive, hormonal contraceptive use alters hormonal cyclicity, which can influence both menstrual cycle features and immune cyclicity, and therefore could potentially affect COVID-19 symptom severity. Some authors have claimed that estradiol, a component of the combined hormonal contraceptive pill, offers a protective effect against COVID-19 severity and mortality, 56 and a study using data from the COVID Symptom Tracker App reported that women aged 18–45 taking the combined oral contraceptive pill had lower rates of predicted COVID-19 and lower hospital attendance than women taking no form of hormone therapy 57 (although the role of residual confounding, most notably by age, cannot be ruled out). Hormonal contraceptive use might also be an effect modifier, for example pandemic-related exposures might affect features of contraceptive-controlled menstrual cycles differently from those of natural cycles.…”

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“…An earlier survey has also emphasized that the incidence of SARS-CoV-2 infection is approximately 15% higher in premenopausal women than men in some age ranges. However, COVID-19 mortality among men is significantly higher than in women of all ages ( 26 ), but this outcome was reverse in some other studies ( 27. , 28.…”