Sex and gender differences in COVID testing, hospital admission, presentation, and drivers of severe outcomes in the DC/Maryland region

Abstract

Background. Rates of severe illness and mortality from SARS-CoV-2 are greater for males, but the mechanisms for this difference are unclear. Understanding the differences in outcomes between males and females across the age spectrum will guide both public health and biomedical interventions. Methods. Retrospective cohort analysis of SARS-CoV-2 testing and admission data in a health system. Patient-level data were assessed with descriptive statistics and logistic regression modeling was used to identify features associated with increased male risk of severe outcomes. Results. In 213,175 SARS-CoV-2 tests, despite similar positivity rates (8.2%F vs 8.9%M), males were more frequently hospitalized (28%F vs 33%M). Of 2,626 hospitalized individuals, females had less severe presenting respiratory parameters and males had more fever. Comorbidity burden was similar, but with differences in specific conditions. Medications relevant for SARS-CoV-2 were used at similar frequency except tocilizumab (M>F). Males had higher inflammatory lab values. In a logistic regression model, male sex was associated with a higher risk of severe outcomes at 24 hours (odds ratio (OR) 3.01, 95%CI 1.75, 5.18) and at peak status (OR 2.58, 95%CI 1.78,3.74) among 18-49 year-olds. Block-wise addition of potential explanatory variables demonstrated that only the inflammatory labs substantially modified the OR associated with male sex across all ages. Conclusion. Higher levels of clinical inflammatory labs are the only features that are associated with the heightened risk of severe outcomes and death for males in COVID-19.

Sex differences in a cohort of COVID-19 Italian patients hospitalized during the first and second pandemic waves.

“…This is in contrast with some recently published data obtained in 340 Italian and Spanish patients in whom cardiovascular disorders were more frequent in males [18]. Instead, our study con rms that asthma occurred more frequently in women [17,29], together with psychiatric, musculoskeletal and rheumatic disorders, and autoimmunity/immune-dysregulation diseases. Of interest, we found a correlation between the presence of multiple comorbidities and a worse prognosis, especially in regard to deaths.…”

“…The presence of multiple comorbidities has been associated with a worse prognosis and higher mortality rate since the start of the COVID-19 pandemic [28]. As also reported by the most recent publications [17,29], we con rmed that cardiovascular diseases and endocrinopathies, especially diabetes mellitus, are the most frequent comorbidities in patients admitted to our hospital, even though with no sex differences. This is in contrast with some recently published data obtained in 340 Italian and Spanish patients in whom cardiovascular disorders were more frequent in males [18].…”

“…This feature has been documented worldwide because a male bias in COVID-19 mortality was reported in the 37 out of the 38 countries that have provided sex disaggregated data [8]. Other studies have also reported that a higher proportion of men were hospitalized than females [17,23]. Our data showed that this is not the case for younger (< 45 years) and older patients (> 75 years), in whom the hospitalizations of females and males were similar.…”

“…While sex-and age-associated differences in COVID-19 patients have been previously investigated, most of the study published so far have involved small cohorts of patients, enrolled in a short period of time, or have been conducted by pooling results of multiple hospitals in the same region or from different Countries, or by performing a metanalysis [14][15][16][17][18]. In addition, not comprehensive clinical and laboratory parameters were analyzed in a single study.…”

Sex Differences in Lung Imaging and SARS-CoV-2 Antibody Responses in a COVID-19 Golden Syrian Hamster Model

“…Ongoing real-time surveillance ( 4 ) and meta-analyses of over 3 million cases of COVID-19 ( 5 ) continue to show that while the incidence of COVID-19 cases is similar between the sexes, adult males are almost 3 times more likely to be admitted into ICUs and twice as likely to die as females. Differential exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely associated with behaviors, occupations, comorbidities, and societal and cultural norms (i.e., gender differences) that impact the probability of exposure, access to testing, utilization of health care, and risk of disease ( 6 – 8 ). This is distinct but also complementary to biological sex differences (i.e., sex chromosome complement, reproductive tissues, and sex steroid hormone concentrations) that can also impact susceptibility and outcomes from COVID-19 ( 9 , 10 ).…”