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

Abstract

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.

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

“…Males typically experience more frequent lower respiratory tract infections [ 112 ] and, in the case of influenza A and B viruses, RSV, SARS-CoV, and other sources of community-acquired pneumonia, more severe disease compared to females [ 113 , 114 ]. Similarly, with SARS-CoV-2 infection, males are hospitalized [ 8 , 115 ], are admitted to intensive care unit (ICU) [ 8 , 116 ] and die [ 117 , 118 ] more often, although infection rates appear to be similar to those of women [ 119 ]. Sex-disaggregated estimates of the infection fatality ratio show consistently higher fatality rates among males in every age category [ 8 , 9 ].…”

Multimorbidity and frailty are associated with poorer SARS-CoV-2-related outcomes: systematic review of population-based studies

“…Bearing in mind that life expectancy is increasing worldwide and even at a faster rate in less-off parts of the world [ 73 ], given the challenges posed by ageing societies, low-income countries, which endured the most devastating effects of the COVID-19 pandemic, should be urged to estimate the relationships investigated here. Multimorbidity manifests differently across age and sex groups [ 74 ], as appears to be the case for the COVID-19 outcomes [ 11 , 75 ]. The studies identified in our review did not provide stratified estimates for these groups.…”

Post-Covid condition and clinic characteristics associated with SARS-CoV-2 infection: a 2-year follow-up to Brazilian cases

“…However, in some patients, a dysfunctional response leads to an intense increase in cytokine release, the cytokine storm, leading to septic shock and multiorgan failure 25 , 26 . In this regard, the differences in immunological response between sexes have been hypothesized to explain increased severity risk in males 27 .…”