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

Abstract

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, and Web 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 studies concerning adult COVID-19 patients: retrospective cohort, observational cohort, case series, and applied research. Further studies were extracted from reference searching. The risk of bias was determined using the National 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, and one genetic study, including a total of 76,555 participants. Ten of the studies included in this review observed a higher risk of mortality among males compared to females, and eight of these studies found this risk to be statistically significant. Sex-disaggregated COVID-19 mortality data identifies male 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 health behaviours as contributing factors to increased risk of mortality from COVID-19 among males. Nine out of the 16 studies included were conducted in China. In order to comprehensively assess sex-differences in the risk of mortality from COVID-19, more studies will need to be conducted worldwide. Sex-disaggregated COVID-19 data 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 is required in order to develop targeted therapies, as well as public health policies, and to prevent sex bias in treatment.

Keywords: covid-19; gender; mortality; review; sex.

Figure 1. PRISMA flow diagram

PRISMA flow diagram to show study identification, screening, inclusion and exclusion against specific pre-defined criteria. COVID-19: coronavirus disease 2019, WHO: World Health Organization, SARS: severe acute respiratory syndrome, MERS: Middle East respiratory syndrome

Figure 2. Male sex and mortality from COVID-19

This figure shows which of the included studies observed an increased risk of mortality due to male sex, and which studies observed a significant association (p<0.05).