This retrospective analysis from 5 Maryland and Washington, DC area hospitals determines factors on hospital admission predictive of severe disease or death from COVID-19 and describes patient trajectories and outcomes categorized using the WHO COVID-19 disease severity scale.

Background Males experience increased severity of illness and mortality from SARS-CoV-2 compared to females but the mechanisms of male susceptibility are unclear. Methods We performed a retrospective cohort analysis of SARS-CoV-2 testing and admission data at 5 hospitals in the Maryland/Washington DC area. Using age-stratified logistic regression models we quantified the impact of male sex on the risk of the composite outcome of severe disease or death (WHO score 5-8), and tested the impact of demographics, comorbidities, health behaviors, and laboratory inflammatory markers on the sex effect. Results Among 213,175 SARS-CoV-2 tests, despite similar positivity rates, males in age strata between 18 and 74 years were more frequently hospitalized. For the 2,626 hospitalized individuals, clinical inflammatory markers (IL-6, CRP, ferritin, absolute lymphocyte count and neutrophil:lymphocyte ratio) were more favorable for females than males (p< 0.001). Among 18-49 year-olds, male sex carried a higher risk of severe outcomes; both early (odds ratio (OR) 3.01, 95%CI 1.75,5.18) and at peak illness during hospitalization (OR 2.58, 95%CI 1.78,3.74). Despite multiple differences in demographics, presentation features, comorbidities and health behaviors, these variables did not change the association of male sex with severe disease. Only clinical inflammatory marker values modified the sex effect, reducing the OR for severe outcomes in males ages 18-49 years to 1.81 (95%CI 1.00,3.26) early and 1.39 (95%CI 0.93,2.08) at peak illness. Conclusions Higher inflammatory laboratory test values were associated with increased risk of severe COVID-19 for males. A sex-specific inflammatory response to SARS-CoV-2 infection may underlie the sex differences in outcomes.

Background. Rates of severe illness and mortality from SARS-CoV-2 are greater for males, but the mechanisms for this difference are unclear. Understanding the differences in outcomes between males and females across the age spectrum will guide both public health and biomedical interventions. Methods. Retrospective cohort analysis of SARS-CoV-2 testing and admission data in a health system. Patient-level data were assessed with descriptive statistics and logistic regression modeling was used to identify features associated with increased male risk of severe outcomes. Results. In 213,175 SARS-CoV-2 tests, despite similar positivity rates (8.2%F vs 8.9%M), males were more frequently hospitalized (28%F vs 33%M). Of 2,626 hospitalized individuals, females had less severe presenting respiratory parameters and males had more fever. Comorbidity burden was similar, but with differences in specific conditions. Medications relevant for SARS-CoV-2 were used at similar frequency except tocilizumab (M>F). Males had higher inflammatory lab values. In a logistic regression model, male sex was associated with a higher risk of severe outcomes at 24 hours (odds ratio (OR) 3.01, 95%CI 1.75, 5.18) and at peak status (OR 2.58, 95%CI 1.78,3.74) among 18-49 year-olds. Block-wise addition of potential explanatory variables demonstrated that only the inflammatory labs substantially modified the OR associated with male sex across all ages. Conclusion. Higher levels of clinical inflammatory labs are the only features that are associated with the heightened risk of severe outcomes and death for males in COVID-19.