A population-based cohort study of sex and risk of severe outcomes in covid-19

• There is a male sex disadvantage in morbidity and mortality due to COVID-19. Proposed explanations to this disparity include gender-related health behaviors, differential distribution of comorbidities and biological sex differences. In this study, we investigated the association between sex and risk of severe COVID-19 while adjusting for comorbidities, socioeconomic factors, as well as unmeasured factors shared by cohabitants which are often left unadjusted. We conducted a total-population-based cohort study (n = 1,854,661) based on individual-level register data. Cox models was used to estimate the associations between sex and risk for severe COVID-19. We additionally used a within-household design and conditional Cox models aiming to account for unmeasured factors shared by cohabitants. A secondary aim was to compare the risk of COVID-19 related secondary outcomes between men and women hospitalized due to COVID-19 using logistic regression. Men were at higher risk for hospitalization (HR = 1.63;95%CI = 1.57–1.68), ICU admission (HR = 2.63;95%CI = 2.38–2.91) and death (HR = 1.81;95%CI = 1.68–1.95) due to COVID-19, based on fully adjusted models. However, the effect of sex varied significantly across age groups: Among people in their 50s, men had > four times higher risk of COVID-19 death. The within-household design did not provide any further explanation to the sex disparity. Among patients hospitalized due to COVID-19, men had an increased risk for viral pneumonia, acute respiratory distress syndrome, acute respiratory insufficiency, acute kidney injury, and sepsis which persisted in fully adjusted models. Recognition of the combined effect of sex and age on COVID-19 outcomes has implications for policy strategies to reduce the adverse effects of the disease.

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