Study reveals sex-based differences in the clinical outcomes of COVID-19 in the US

In a recent study posted to the Research Square* preprint server, researchers investigated sex-based differences among coronavirus disease 2019 (COVID-19) patients in the United States (US).

Studies have reported greater severity and fatality associated with COVID-19 among men compared to women across the globe; however, the mechanisms for sex-based differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are not clear. Previous research observations indicate that researchers must consider the patients’ sex as an important variable for COVID-19 data interpretation.

About the study

In the present study, researchers explored the sex-based differences in sociodemographic characteristics, lifestyle factors, and comorbidities among COVID-19 patients.

This study comprised 62,310 male and female COVID-19 patients with diagnoses confirmed between January 2020 and December 2021 by polymerase chain reaction (PCR) and immunoglobulin G (IgG)/IgM analysis. Data were retrospectively obtained from the COVID-19 Research Database. In addition, secondary data were extracted from the Healthjump database pertaining to the patients’ medical claim records and electronic health records (EHRs).

The EHRs comprised medical and social history (race, language, ethnicity), demographics (sex, age), vitals (such as blood pressure, oxygen saturation), vaccination, medications, and diagnosis (e.g., diabetes, hypertension, etc), appointments, procedures, and encounters. Logistic regression models were used for the analysis and the adjusted odds ratios (AOR) were determined.

Results and discussion

An age-dependent rise in COVID-19 cases was observed for men and women and individuals most severely affected were aged 50 to 59 years comprising 3,628 men and 6,418 women. Among the study participants, 13%, 9.4%, 12.3%, 15.5%, 17.7%, 16.3% and 15.9% were aged <20 years, 20 to 29 years, 30 to 39 years, 40 to 49 years, 50 to 59 years, 60 to 69 years and >70 years, respectively.

Substantial differences in comorbidities and socio-demographics were noted between female and male patients, e.g., a substantially greater proportion of men (vs. women) were aged >70 years (17% vs. 15%) and were smokers (11% vs. 9.2%, (OR = 1.4). Additionally, diabetes (8.8% versus 6.5%) and hypertension (4.4% versus 3.9%) were substantially more commonly observed among men compared to women with AOR values of 22.9 and 66.2, respectively. Pneumonia and influenza were more likely among men compared to women (OR = 66.2).

Substantial sex-based differences were noted in laboratory parameters, comorbidities, and vaccinations among SARS-CoV-2-positive individuals. A slightly higher proportion of SARS-CoV-2-positive men presented with mild hypoxemia compared to females (9.3% versus 7.1%, (OR = 1.3). A greater proportion of men reported use of caffeine (77.4% versus 75.9%), alcohol (30.7% versus 22.4%) and drugs (6.6% versus 5.2%) and were obese (55.1% versus 54.3%) or overweight (31% vs. 26%).

On the other hand, a greater proportion of women compared to men had health services encounters for genetic susceptibility tests and clinical examinations (14.6% versus 13.9%), thyroid disorders (4.4% versus 2.5%) and stress-related dissociative and other mental illnesses and anxiety (2.9% versus 1.9%), although males suffered substantially more from personality and behavioral disorders and intellectual disabilities compared to females (OR = 89.7). Further, no substantial sex-based differences were noted concerning living arrangements, transportation, vaccines, and exercises.

Male SARS-CoV-2-positive patients demonstrated a higher frequency of comorbid conditions such as hypertension and diabetes, and abnormal laboratory and clinical findings based on data adjustments for covariates such as education, ethnicity, and age. The present study findings were in accordance with studies on COVID-19 conducted in Europe, China, and the US that reported a disproportionate impact of COVID-19 among males and females.

The study findings showed a strong and independent association between the male gender and enhanced susceptibility to COVID-19. Men have been reported to be more frequently involved in risky practices, such as alcohol consumption and smoking. Further, smoking habits have been associated with adverse COVID-19 outcomes since smoking elevates the pulmonary angiotensin-converting enzyme 2 (ACE2) expression and therefore increases SARS-CoV-2 invasion in the host, which may explain the association between smoking and COVID-19 severity. Furthermore, alcohol intake and smoking predispose males to comorbidities such as pulmonary disorders and cardiovascular disorders.

Sex-based differences are intertwined with role or social differences between men and women which influence the outcomes of COVID-19. Men commonly work in occupations and sectors that require social interactions (e.g., agriculture, production and/or distribution of food, pharmacy or food sales and manufacturing, security, and transportation). Increased social gatherings including mask removal to smoke and drink increase SARS-CoV-2 exposure among men.

Furthermore, males and females respond differently to self and foreign antigens with sex-based immunological differences. Studies have reported greater interleukin (IL)-8 and 18 cytokine expression among men whereas enhanced T lymphocyte activation among females in COVID-19 and an association of poor T lymphocyte responses with COVID-19 outcomes.

Conclusion

Overall, the study findings highlighted the sex-based differences in lifestyle factors, comorbidities, and sociodemographic characteristics in COVID-19, an understanding of which would aid in clinical decision-making to provide medical care to COVID-19 patients. In addition, the findings would inform COVID-19 policy-making and improve the global preparedness and efficacy of health interventions.

*Important notice

Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.