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

  • Mohamad Alkhouli
    Correspondence
    Correspondence: Address to Mohamad Alkhouli, MD, Department of Cardiovascular Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
    Affiliations
    Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
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  • Aravinda Nanjundappa
    Affiliations
    Department of Medicine, Division of Cardiology, Charleston Area Medical Center Institute (CAMC) for Academic Medicine and CAMC Health, Education and Research Institute, Charleston, WV

    Department of Medicine, Division of Cardiology, West Virginia University, Charleston Division, Charleston, WV
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  • Frank Annie
    Affiliations
    Department of Medicine, Division of Cardiology, Charleston Area Medical Center Institute (CAMC) for Academic Medicine and CAMC Health, Education and Research Institute, Charleston, WV
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  • Mark C. Bates
    Affiliations
    Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN

    Department of Medicine, Division of Cardiology, Charleston Area Medical Center Institute (CAMC) for Academic Medicine and CAMC Health, Education and Research Institute, Charleston, WV
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  • Deepak L. Bhatt
    Affiliations
    Department of Medicine, Division of Cardiology, Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, MA
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      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.

      Abbreviations and Acronyms:

      ACE2 (angiotensin-converting enzyme 2), ACEI (angiotensin-converting enzyme inhibitor), ARB (angiotensin receptor blocker), COVID-19 (coronavirus disease 2019), PSM (propensity score matching), SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)
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