TY - JOUR
T1 - The "sex gap" in COVID-19 trials
T2 - a scoping review
AU - Schiffer, Veronique M M M
AU - Janssen, Emma B N J
AU - van Bussel, Bas C T
AU - Jorissen, Laura L M
AU - Tas, Jeanette
AU - Sels, Jan-Willem E M
AU - Bergmans, Dennis C J J
AU - Dinh, Trang H T
AU - van Kuijk, Sander M J
AU - Hana, Anisa
AU - Mehagnoul-Schipper, Jannet
AU - Scheeren, Clarissa I E
AU - Mesotten, Dieter
AU - Stessel, Bjorn
AU - Marx, Gernot
AU - Hof, Arnoud W J van T
AU - Spaanderman, Marc E A
AU - van Mook, Walther N K A
AU - van der Horst, Iwan C C
AU - Ghossein-Doha, Chahinda
N1 - © 2020 The Authors.
PY - 2020/12
Y1 - 2020/12
N2 - 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: 30 studies were eligible for inclusion, investigating remdesivir (n = 2), lopinavir/ritonavir (n = 5), favipiravir (n = 1), umifenovir (n = 1), hydroxychloroquine/chloroquine (n = 8), convalescent plasma (n = 6), interleukin-6 (IL-6) pathway inhibitors (n = 5), interleukin-1 (IL-1) pathway inhibitors (n = 1) and corticosteroids (n = 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.
AB - 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: 30 studies were eligible for inclusion, investigating remdesivir (n = 2), lopinavir/ritonavir (n = 5), favipiravir (n = 1), umifenovir (n = 1), hydroxychloroquine/chloroquine (n = 8), convalescent plasma (n = 6), interleukin-6 (IL-6) pathway inhibitors (n = 5), interleukin-1 (IL-1) pathway inhibitors (n = 1) and corticosteroids (n = 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.
KW - CORONAVIRUS DISEASE 2019
KW - COVID-19
KW - Clinical trials
KW - Diversity
KW - GENDER
KW - HYDROXYCHLOROQUINE
KW - OUTCOMES
KW - PNEUMONIA
KW - Sex
KW - TMPRSS2
KW - Therapy
KW - GENDER-DIFFERENCES
U2 - 10.1016/j.eclinm.2020.100652
DO - 10.1016/j.eclinm.2020.100652
M3 - (Systematic) Review article
C2 - 33283178
SN - 2589-5370
VL - 29-30
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 100652
ER -