Background: Emerging evidence from China suggests that coronavirus disease 2019 (COVID-19) is deadlier for infected men than women with a 2.8% fatality rate being reported in Chinese men versus 1.7% in women. Further, sex-disaggregated data for COVID-19 in several European countries show a similar number of cases between the sexes, but more severe outcomes in aged men. Case fatality is highest in men with pre-existing cardiovascular conditions. The mechanisms accounting for the reduced case fatality rate in women are currently unclear but may offer potential to develop novel risk stratification tools and therapeutic options for women and men.Content: The present review summarizes latest clinical and epidemiological evidence for gender and sex differences in COVID-19 from Europe and China. We discuss potential sex-specific mechanisms modulating the course of disease, such as hormone-regulated expression of genes encoding for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) entry receptors angiotensin converting enzyme (ACE) 2 receptor and TMPRSS2 as well as sex hormone-driven innate and adaptive immune responses and immunoaging. Finally, we elucidate the impact of gender-specific lifestyle, health behavior, psychological stress, and socioeconomic conditions on COVID-19 and discuss sex specific aspects of antiviral therapies.Conclusion: The sex and gender disparities observed in COVID-19 vulnerability emphasize the need to better understand the impact of sex and gender on incidence and case fatality of the disease and to tailor treatment according to sex and gender. The ongoing and planned prophylactic and therapeutic treatment studies must include prospective sex- and gender-sensitive analyses.

Gender—the socially constructed roles, behaviours, activities and attributes that a given society considers appropriate for males, females and other genders—affects how people live, work and relate to each other at all levels, including in relation to the health system. Health systems research (HSR) aims to inform more strategic, effective and equitable health systems interventions, programs and policies; and the inclusion of gender analysis into HSR is a core part of that endeavour. We outline what gender analysis is and how gender analysis can be incorporated into HSR content, process and outcomes . Starting with HSR content, i.e. the substantive focus of HSR, we recommend exploring whether and how gender power relations affect females and males in health systems through the use of sex disaggregated data, gender frameworks and questions. Sex disaggregation flags female–male differences or similarities that warrant further analysis; and further analysis is guided by gender frameworks and questions to understand how gender power relations are constituted and negotiated in health systems. Critical aspects of understanding gender power relations include examining who has what (access to resources); who does what (the division of labour and everyday practices); how values are defined (social norms) and who decides (rules and decision-making). Secondly, we examine gender in HSR process by reflecting on how the research process itself is imbued with power relations. We focus on data collection and analysis by reviewing who participates as respondents; when data is collected and where; who is present; who collects data and who analyses data. Thirdly, we consider gender and HSR outcomes by considering who is empowered and disempowered as a result of HSR, including the extent to which HSR outcomes progressively transform gender power relations in health systems, or at least do not further exacerbate them.

Immunotherapies are often used for the treatment, remission, and possible cure of autoimmune diseases, infectious diseases, and cancers. Empirical evidence illustrates that females and males differ in outcomes following the use of biologics for the treatment of autoimmune diseases, e.g., rheumatoid arthritis (RA), infectious diseases, e.g., influenza, and solid tumor cancers. Females tend to experience more adverse reactions than males following the use of a class of biologics referred to as immunotherapies. For immunotherapies aimed at stimulating an immune response, e.g., influenza vaccines, females develop greater responses and may experience greater efficacy than males. In contrast, for immunotherapies that repress an immune response, e.g., tumor necrosis factor (TNF) inhibitors for RA or checkpoint inhibitors for melanoma, the efficacy is reportedly greater for males than females. Despite these differences, discrepancies in reporting differences between females and males exist, with females have been historically excluded from biomedical and clinical studies. There is a critical need for research that addresses the biological (i.e., sex) as well as sociocultural (i.e., gender) causes of male-female disparities in immunotherapy responses, toxicities, and outcomes. One-size-fits-all approaches to immunotherapies will not work, and sex/gender may contribute to variable treatment success, including adherence, in clinical settings.

Intersectionality has emerged as an important framework for understanding and responding to health inequities by making visible the fluid and interconnected structures of power that create them. It promotes an understanding of the dynamic nature of the privileges and disadvantages that permeate health systems and affect health. It considers the interaction of different social stratifiers (e.g. ‘race’/ethnicity, indigeneity, gender, class, sexuality, geography, age, disability/ability, migration status, religion) and the power structures that underpin them at multiple levels. In doing so, it is a departure from previous health inequalities research that looked at these forms of social stratification in isolation from one another or in an additive manner. Despite its potential use and long history in other disciplines, intersectionality is uncommonly used in health systems research in low- and middle-income countries (LMICs). To orient readers to intersectionality theory and research, we first define intersectionality and describe its role in public health, and then we review resources on intersectionality. We found that applications in public health mostly increased after 2009, with only 14 out of 86 articles focused on LMICs. To arrive at 10 best resources, we selected articles based on the proportion of the article that was devoted to intersectionality, the strength of the intersectionality analysis, and its relevance to LMICs. The first four resources explain intersectionality as a methodology. The subsequent six articles apply intersectionality to research in LMIC with quantitative and qualitative analysis. We provide examples from India, Swaziland, Uganda and Mexico. Topics for the studies range from HIV, violence and sexual abuse to immunization and the use of health entitlements. Through these 10 resources, we hope to spark interest and open a needed conversation on the importance and use of intersectional analysis in LMICs as part of understanding people-centred health systems.