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

Abstract

Objectives: To confirm whether a relationship exists between male sex and coronavirus disease 2019 (COVID-19) mortality and whether this relationship is age dependent.

Patients and methods: We queried the COVID-19 Research Network, a multinational database using the TriNetX network, to identify patients with confirmed COVID-19 infection. The main end point of the study was all-cause mortality.

Results: A total of 14,712 patients were included, of whom 6387 (43%) were men. Men were older (mean age, 55.0±17.7 years vs 51.1±17.9 years; P<.001) and had a 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 rate was 8.8% in men and 4.3% in women (odds ratio, 2.15; 95% CI, 1.87 to 2.46; P<.001) at a median follow-up duration of 34 and 32 days, respectively. In the Kaplan-Meier survival analysis, the cumulative probability of survival was significantly lower in men than in women (73% vs 86%; log-rank, P<.001). After PSM, all-cause mortality remained significantly higher in men than in women (8.13% vs 4.60%; odds ratio, 1.81; 95% CI, 1.55 to 2.11; P<.001). In the Kaplan-Meier survival analysis, the cumulative probability of survival remained significantly lower in men than in women (74% vs 86%; log-rank, P<.001). The cumulative probability of survival remained significantly lower in propensity score-matched men than in women after excluding patients younger than 50 years and those who were taking angiotensin-converting enzyme inhibitor or angiotensin receptor blocker medications on admission.

Conclusion: Among patients with COVID-19 infection, men had a significantly higher mortality than did women, and this difference was not completely explained by the higher prevalence of comorbidities in men.

Figure 1

Kaplan-Meier survival analysis of the study groups before propensity score matching.

Figure 2

Kaplan-Meier survival analysis of the study groups after propensity score matching. Variables used for propensity score matching included hypertension, diabetes, chronic obstructive lung disease, heart failure, obesity, nicotine dependence, and history of stroke.

Figure 3

Kaplan-Meier survival in propensity score–matched patients 50 years and older. Variables used for propensity score matching included hypertension, diabetes, chronic obstructive lung disease, heart failure, obesity, nicotine dependence, and history of stroke, with exclusion of patients older than 50 years.

Figure 4

Kaplan-Meier survival excluding patients taking angiotensin-converting enzyme inhibitor or angiotensin receptor blocker medications. Variables used for propensity score matching included hypertension, diabetes, chronic obstructive lung disease, heart failure, obesity, nicotine dependence, and history of stroke, with exclusion of patients taking angiotensin-converting enzyme inhibitor or angiotensin receptor blocker medications.