Analysis of sex-specific risk factors and clinical outcomes in COVID-19

Background Sex has consistently been shown to affect COVID-19 mortality, but it remains unclear how each sex’s clinical outcome may be distinctively shaped by risk factors. Methods We studied a primary cohort of 4930 patients hospitalized with COVID-19 in a single healthcare system in New York City from the start of the pandemic till August 5, 2020, and a validation cohort of 1645 patients hospitalized with COVID-19 in the same healthcare system from August 5, 2020, to January 13, 2021. Results Here we show that male sex was independently associated with in-hospital mortality, intubation, and ICU care after adjusting for demographics and comorbidities. Using interaction analysis and sex-stratified models, we found that hypoxia interacted with sex to preferentially increase women’s mortality risk while obesity interacted with sex to preferentially increase women’s risk of intubation and intensive care in our primary cohort. In the validation cohort, we observed that male sex remained an independent risk factor for mortality, but sex-specific interactions were not replicated. Conclusions We conducted a comprehensive sex-stratified analysis of a large cohort of hospitalized COVID-19 patients, highlighting clinical factors that may contribute to sex differences in the outcome of COVID-19. Plain Language Summary Men are at higher risk of death from COVID-19 than women, but the underlying reasons are not fully understood. We examined the medical data of men and women hospitalized with COVID-19 in New York City to determine whether there were factors which raised the risk of death or requiring intensive care more for one sex rather than the other. We observed that men hospitalized with COVID-19 had a higher risk of death than women when other factors taken into account. Some conditions, like low oxygen levels and obesity, appeared to be associated with worse outcomes in women compared to men early in the pandemic but further studies will be necessary for confirmation. These findings highlight groups of men and women who may be at increased risk of severe COVID-19. Jun et al. evaluate sex-stratified clinical outcomes in two cohorts of patients hospitalized with COVID-19 in New York. While male sex risk is a risk factor for poor outcome in both cohorts – one from earlier and one from later on in the pandemic – some of the sex-specific risk factors observed initially are not observed later on.