Outcome Disparities Among Men and Women With COVID-19: An Analysis of the New York City Population Cohort

October 2020 | Volume 19 | Issue 10 | Original Article | 960 | Copyright © October 2020


Published online October 2, 2020

Nahid Punjani MD MPHa, b, Albert Ha MDc, Joseph Caputo MDc, Vinson Wang MDc, Lisa Wiechmann MDd, Mary Ann Chiasson DrPHb,e, Philip Li MDa, James Hotaling MD MSf, Thomas Walsh MD MSg, Joseph Alukal MDc

aDepartment of Urology, Center for Male Reproductive Medicine and Microsurgery, Weill Cornell Medicine, New York, NY bDepartment of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY cDepartment of Urology, New York-Presbyterian Columbia University Irving Medical Center, New York, NY dDepartment of General Surgery, New York-Presbyterian Columbia University Irving Medical Center, New York, NY eDivision of Infectious Diseases, Department of Medicine, New York-Presbyterian Columbia University Irving Medical Center, New York, NY fDepartment of Urology, University of Utah, Salt Lake City, UT gDepartment of Urology, University of Washington, Seattle, WA







Data were missing for almost 20% of each gender group. The relative risk of having a comorbidity was 0.99 (95%CI 0.99–0.99) when comparing men and women dying from COVID-19.

The case fatality rate for the entire cohort was 10.6% (Table 4). Men had a greater CFR overall compared to women (12.28% vs 8.93%). In every age category, men had higher CFRs compared to age-matched female counterparts with the most significant difference in the 65–74 age category (24.78% in men versus 16.16% in women).

DISCUSSION

The COVID-19 pandemic has had an immeasurable impact, affecting healthcare systems, the global economy, and society as a whole. Exploration of trends within the existing COVID-19 data may guide directions for further study and novel treatment development. Our analysis demonstrates that despite higher absolute rates of testing in women in NYC, men in almost every age group had higher rates of test positivity, hospitalization and death. These findings persist after stratification for age. Our findings represent the largest current COVID-19 series of age matched data from a metropolitan region and elaborate upon trends observed in other countries across the globe.5

While our data represent a single metropolitan region (NYC), they mirror data from over 50 countries across six continents. In all but one country (Portugal), rates of death were equivalent or greater in men versus women, with an estimated 60% increased risk of severe illness or death.5 Interestingly, many European countries report increased rates of female case positivity.5,8 Larger datasets from other COVID-19 epicenters, Italy and China, demonstrate increased case numbers and poorer outcomes in men, but this may be confounded by comorbidities and lifestyle behaviors.8

Men aged 18–44, 45–64, and 65–74 were more likely than age matched women to be hospitalized or die as a result of COVID. This may be attributable to a sex-based physiologic difference in the course of the disease; this may be hormonal and/or nonhormonal, but also may be due to the underlying mechanism of disease. Pathophysiologically, SARS-CoV-2 viral spike proteins bind to the angiotensin converting enzyme-2 (ACE2) receptor, and are primed by acellular serine protease (TMPRSS2), ultimately facilitating entry into cells.9 Studies demonstrate ACE2 and TMPRSS2 expression throughout the body, including the prostate and testis.10 ACE2 expression is controlled by the X-chromosome, and therefore X-linked gene inactivation in women may be relevant.11 ACE2 expression within the testis occurs in both Sertoli and Leydig cells as well as in spermatogonia and spermatids.10 TMPRSS2 gene fusions (TMPRSS2-ERG) are involved in the development and progression of some prostate cancers.12 Expression levels of both ACE2 and TMPRSS2 were detected at low levels in the testis, but co-expression was less than <0.1% suggesting that direct entry into testis was unlikely to occur.13 In contrast, testicular or scrotal discomfort concerning for viral orchitis is reported with COVID-19. This condition was also reported with the original SARS coronavirus.13,14 There is limited data regarding viral positivity in the testis, and no studies have assessed viral shedding in extra-prostatic secretions.15,16 Overall, this suggests that ACE2 and TMPRSS2 expression in male specific organs may not provide an adequate explanation for this observed sex disparity.