Sex-bias in COVID-19: a meta-analysis and review of sex differences in disease and immunity

Abstract

A striking anecdotal feature of the Coronavirus disease 2019 (COVID-19) outbreak is the difference in morbidity and mortality between the sexes. Here, we present a meta-analysis of 206, 128 reported cases to demonstrate that whilst there is no difference in the proportion of males and females with confirmed COVID-19, male patients have more than double the odds of requiring intensive treatment unit admission (OR 2.5) and higher odds of death (OR 1.60) when compared to females. We review data revealing how previous Coronavirus outbreaks have demonstrated a similar pattern. Important differences in the immune response to infection exist between sexes, which are likely to contribute to this observation. In this review, we discuss these differences highlighting that females have a more robust innate antiviral response and a better adaptive immune response to infection. An appreciation of how sex is influencing COVID-19 outcomes will have important implications for clinical management and mitigation strategies for this disease.

Asymptomatic SARS-CoV-2 infection in two patients with multiple sclerosis treated with fingolimod

“…This favorable COVID-19 course, might be partially explained by the fact that all affected individuals were relatively young, which is a good prognostic feature ( Kronbichler et al., 2020 ; Oran and Topol, 2020 ) . Of note recent papers have highlighted that asymptomatic cases are more frequently young and female ( Meng et al., 2020 ; Peckham et al., 2020 ).…”

Could Sex/Gender Differences in ACE2 Expression in the Lungs Contribute to the Large Gender Disparity in the Morbidity and Mortality of Patients Infected With the SARS-CoV-2 Virus?

“…This large gender difference has been shown both in China (Guan et al, 2020;Jin et al, 2020), the first country affected by , and recently in Italy (Riccardo et al, 2020), a country that is currently, in the middle of March 2020, the most affected by this disease. A preprint reporting a meta-analysis of 39 reports, including 206,128 patients, confirms the sex bias, with much higher mortality and more severe presentation of the disease in men in several countries affected by COVID-19 throughout the world (Peckham et al, 2020). Age is another risk factor for both morbidity and mortality in COVID-19 patients, with children seemingly mostly resistant to the effects of the SARS-CoV-2 virus (Lu et al, 2020).…”

Sex-bias in COVID-19-associated illness severity and mortality in cancer patients: A systematic review and meta-analysis

“…Early observational findings suggested that Coronavirus disease 2019 (COVID-19) is associated with disproportionately worse outcomes in males compared to females with subsequent studies providing statistical evidence for this clinical phenomenon and indicating that morbidity and mortality are higher in males despite no difference in the proportion of infected cases between the sexes [ 1 , 2 ]. As yet, the pathogenesis behind this sex-bias is not established, although a number of theories have been proposed.…”