The “sex gap” in COVID-19 trials: a scoping review
Véronique Schiffer, Emma B N J Janssen, Bas C. T. van Bussel, Laura L.M. Jorissen, Jeanette Tas, Jan-Willem Sels, Dennis C. J. J. Bergmans, Trang Dinh, Sander M. J. van Kuijk, Anisa Hana, Jannet Mehagnoul-Schipper, Clarissa Scheeren, Dieter Mesotten, Björn Stessel, Gernot Marx, Arnoud W.J. van ‘t Hof, Marc E. A. Spaanderman, Walther van Mook, Iwan C.C. van der Horst, Chahinda Ghossein‐Doha
Abstract
BACKGROUND: Many studies investigate the role of pharmacological treatments on disease course in Corona Virus Disease 2019 (COVID-19). Sex disparities in genetics, immunological responses, and hormonal mechanisms may underlie the substantially higher fatality rates reported in male COVID-19 patients. To optimise care for COVID-19 patients, prophylactic and therapeutic studies should include sex-specific design and analyses. Therefore, in this scoping review, we investigated whether studies on pharmacological treatment in COVID-19 were performed based on a priori sex-specific design or post-hoc sex-specific analyses. METHODS: We systematically searched PubMed, EMBASE, UpToDate, clinical trial.org, and MedRxiv for studies on pharmacological treatment for COVID-19 until June 6th, 2020. We included case series, randomized controlled trials, and observational studies in humans (≥18 years) investigating antiviral, antimalarial, and immune system modulating drugs. Data were collected on 1) the proportion of included females, 2) whether sex stratification was performed (a priori by design or post-hoc), and 3) whether effect modification by sex was investigated. FINDINGS: = 3). Only one study stratified its data based on sex in a post-hoc analysis, whereas none did a priori by design. None of the studies investigated effect modification by sex. A quarter of the studies included twice as many males as females. INTERPRETATION: Analyses assessing potential interference of sex with (side-)effects of pharmacological therapy for COVID-19 are rarely reported. Considering sex differences in case-fatality rates and genetic, immunological, and hormonal mechanisms, studies should include sex-specific analyses in their design to optimise COVID-19 care. FUNDING: None.