Sex Differences in the Coronavirus Disease 2019

Abstract

There are profound sex differences in coronavirus disease 2019 (COVID-19) outcomes, with higher morbidity and mortality in males compared to females. The possible mechanisms implicated in this sex bias include the direct effects of sex hormones on the innate and adaptive immune systems, as well as the differential activity of immune-related genes in sex chromosomes. These male-female differences in COVID-19 outcomes highlight the need for sex-disaggregated data to elaborate effective public health policies and the importance of including biological sex as a key variable in future therapeutic and vaccine trials.

Gender and sex bias in COVID-19 epidemiological data through the lens of causality

“…Moreover, biological differences in the immune systems of men and women exist, and they may affect the capacity to fight COVID-19 infection. Men appear to be at a greater risk with COVID-19 compared to women, whose higher immunologic response is probably associated with decreased mortality ( Chiarella, Pabelick, & Prakash, 2021 ). Furthermore, certain differences in cardiac manifestations in COVID-19 must be considered as a core component ( Sharma, Volgman, & Michos, 2020 ).…”

“…A confounder is a variable with incoming arrows in the graph to both sensitive attribute and an outcome (a cause for both) and creates spurious non causal relationship between the two. Variable and source Class Group Comments Hormones ( Chiarella et al, 2021 , Dana et al, 2020 , Klein et al, 2020 , Peckham et al, 2020 , Traish and Morgentaler, 2021 ) Mediator Sex-related Bio Var Male hormone testosterone is associated with increased vulnerability, whereas female hormones are believed to play a protecting role. Immune response ( Chiarella et al, 2021 , Dana et al, 2020 , Grzelak et al, 2020 ) Mediator Sex-related Bio Var More protective antibodies are formed in women and they last longer.…”

“… Variable and source Class Group Comments Hormones ( Chiarella et al, 2021 , Dana et al, 2020 , Klein et al, 2020 , Peckham et al, 2020 , Traish and Morgentaler, 2021 ) Mediator Sex-related Bio Var Male hormone testosterone is associated with increased vulnerability, whereas female hormones are believed to play a protecting role. Immune response ( Chiarella et al, 2021 , Dana et al, 2020 , Grzelak et al, 2020 ) Mediator Sex-related Bio Var More protective antibodies are formed in women and they last longer. Smoking and drinking ( Bwire, 2020 , Gebhard et al, 2020 ) Mediator Gender-related Lifestyle Var Higher smoking and drinking rates among men induce lung injuries that affect COVID-19 vulnerability.…”

Sex differences in hospitalized COVID-19 patients

“…Since the beginning of the pandemic, in several countries there was the need to collect sex-disaggregated data in order to evaluate the incidence, the mortality rate and the disease treatment according to the sex. Importantly, demographic and clinical data collected globally demonstrated that the rate of COVID-19, including asymptomatic and mild forms, is similar between the sexes [11]. Instead, in our data, which include only patients hospitalized and who had attended emergency room, the percentage of females was lower than that of males both in the first and the second wave.…”

“…There is a significant sex bias in the immune response to viral infections. This bias is considered the result of male-female differences in sex chromosomes and sex hormone milieu [11]. In general, female immune system responds to pathogens more efficiently, producing higher amounts of interferon (INF) and antibodies.…”