新冠病毒疾病试验中的“性别差异”：一项范围综述
The "sex gap" in COVID-19 trials: a scoping review.
作者信息
Schiffer Veronique M M M, Janssen Emma B N J, van Bussel Bas C T, Jorissen Laura L M, Tas Jeanette, Sels Jan-Willem E M, Bergmans Dennis C J J, Dinh Trang H T, van Kuijk Sander M J, Hana Anisa, Mehagnoul-Schipper Jannet, Scheeren Clarissa I E, Mesotten Dieter, Stessel Bjorn, Marx Gernot, Hof Arnoud W J van T, Spaanderman Marc E A, van Mook Walther N K A, van der Horst Iwan C C, Ghossein-Doha Chahinda
机构信息
Department of Obstetrics and Gynaecology, Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands.
GROW, School for Oncology and Developmental Biology, Maastricht University, the Netherlands.
出版信息
EClinicalMedicine. 2020 Dec;29:100652. doi: 10.1016/j.eclinm.2020.100652. Epub 2020 Nov 30.
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 ( = 2), lopinavir/ritonavir ( = 5), favipiravir ( = 1), umifenovir ( = 1), hydroxychloroquine/chloroquine ( = 8), convalescent plasma ( = 6), interleukin-6 (IL-6) pathway inhibitors ( = 5), interleukin-1 (IL-1) pathway inhibitors ( = 1) and corticosteroids ( = 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.
背景
许多研究探讨了药物治疗在2019冠状病毒病（COVID-19）病程中的作用。男性COVID-19患者报告的死亡率显著更高，其原因可能在于遗传、免疫反应和激素机制方面的性别差异。为了优化对COVID-19患者的护理，预防性和治疗性研究应纳入针对性别的设计和分析。因此，在本范围综述中，我们调查了关于COVID-19药物治疗的研究是否基于预先设定的针对性别的设计或事后针对性别的分析。
方法
我们系统检索了PubMed、EMBASE、UpToDate、clinicaltrial.org和MedRxiv，以查找截至2020年6月6日关于COVID-19药物治疗的研究。我们纳入了病例系列、随机对照试验以及针对人类（≥18岁）的观察性研究，这些研究调查了抗病毒、抗疟和免疫系统调节药物。收集的数据包括：1）纳入女性的比例；2）是否进行了性别分层（预先设计或事后分析）；3）是否研究了性别对效应的修饰作用。
结果
30项研究符合纳入标准，研究对象包括瑞德西韦（n = 2）、洛匹那韦/利托那韦（n = 5）、法匹拉韦（n = 1）、乌米芬诺尔（n = 1）、羟氯喹/氯喹（n = 8）、康复期血浆（n = 6）、白细胞介素-6（IL-6）通路抑制剂（n = 5）、白细胞介素-1（IL-1）通路抑制剂（n = 1）和皮质类固醇（n = 3）。只有一项研究在事后分析中按性别对数据进行了分层，而没有研究是基于预先设计进行的。没有一项研究调查性别对效应的修饰作用。四分之一的研究纳入的男性数量是女性的两倍。
解读
很少有研究报告评估性别对COVID-19药物治疗（副作用）潜在干扰的分析。考虑到病死率以及遗传、免疫和激素机制方面的性别差异，研究应在设计中纳入针对性别的分析，以优化对COVID-19患者的护理。
资金来源
无。
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