The Role of Sex in the Risk of Mortality From COVID-19 Amongst Adult Patients: A Systematic Review

A worldwide outbreak of coronavirus disease 2019 (COVID-19), identified as being caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), was classified as a Public Health Emergency of International Concern by the World Health Organisation (WHO) on January 30, 2020. Initial sex-disaggregated mortality data emerging from the Wuhan province of China identified male sex as a risk factor for increased COVID-19 mortality. In this systematic review, we aimed to assess the role of sex in the risk of mortality from COVID-19 in adult patients through comparison of clinical markers and inflammatory indexes. A systematic search was conducted on the following databases:PubMed, WHO COVID-19 database, Ovid MEDLINE, andWeb of Science between the dates of June 15, 2020, and June 30, 2020.Key search terms used included: "sex", "gender", "SARS-COV-2","COVID" and "mortality".We accepted the following types of studiesconcerning adult COVID-19 patients: retrospectivecohort, observationalcohort, case series, and applied research.Further studies were extracted from referencesearching.The risk of bias was determined using theNational Institutes of Health Quality Assessment Tool for Observational Cohort, Cross-Sectional Studies, and Case Series. We identified a total of 16 studies published between January 2020 and June 2020 for analysis in this systematic review. Our study population consisted of 11 cohort studies,four case series, andonegenetic study, including a total of 76,555 participants. Ten of the studiesincluded in this review observeda higher risk of mortality amongmalescompared to females, and eight of these studies found this risk to be statistically significant. Sex-disaggregated COVID-19 mortalitydata identifiesmale patients with comorbidities as being at an increased risk of mortality worldwide. Further investigation revealed differences in immune response regulated by sex hormones, angiotensin-converting enzyme 2 (ACE2) expression, and healthbehavioursas contributing factors to increased risk of mortality from COVID-19 among males. Nineout of the16studies included were conducted in China.In order tocomprehensively assess sex-differences in the risk of mortality from COVID-19, more studies will need to be conducted worldwide.Sex-disaggregatedCOVID-19data published in the medical literature is limited,however it has become evident that male sex is an important risk factor for mortality.Further exploration into the impact of sex on this pandemic isrequiredin order todevelop targeted therapies, as well as public health policies,and to prevent sex bias in treatment.