Sex Differences in COVID-19 Case Fatality Rate: Insights From a Multinational Registry

Alkhouli, Mohamad; Nanjundappa, Aravinda; Annie, Frank; Bates, Mark C.; Bhatt, Deepak L.

Abstract Objective To confirm whether a relationship exists between male sex and coronavirus disease 2019 (COVID-19) mortality and if this relationship is age-dependent. Methods We queried the COVID-19 Research Network; a multinational database utilizing the TriNetX Network to identify patients with confirmed COVID-19 infection. The main endpoint of the study was all-cause mortality. Results 14,712 patients were included, of whom, 6,387 (43.4%) were males. Males were older (55.0±17.7 vs. 51.1±17.9 years, P<.001), and had higher prevalence of hypertension, diabetes, coronary disease, obstructive pulmonary disease, nicotine dependence and heart failure, but a lower prevalence of obesity. Before propensity score matching (PSM), all-cause mortality was 8.8% in males and 4.3% in females (OR 2.15; 95% CI, 1.87-2.46; P<.001), at median follow-up of 34, and 32 days, respectively. In the Kaplan Meier survival analysis, the cumulative probability of survival was significantly lower in males than in females (73% vs. 86%, P-log rank <.001). After PSM, all-cause mortality remained significantly higher in males than in females (8.13% vs. 4.60%, OR 1.81; 95% CI, 1.55-2.11; P<.001). In the Kaplan Meier survival analysis, the cumulative probability of survival remained significantly lower in males than in females (74% vs. 86%, P-log rank <.001). The cumulative probability of survival remained significantly lower in PSM males than females after excluding patients <50 years of age, and those who were taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blocker (ARB) on admission. Conclusion Among patients with COVID-19 infection, males had significantly higher mortality than females, and this difference was not completely explained by the higher prevalence of co-morbidities in males.