What is the effect of sex on the clinical characteristics and prognosis of COVID-19 patients?

By Pooja Toshniwal PahariaFeb 3 2023Reviewed by Danielle Ellis, B.Sc.

In a recent study published in the Journal of Clinical Medicine, researchers evaluated coronavirus disease 2019 (COVID-19) management based on sex differences.

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused unprecedented morbidity and mortality across the globe. Previous studies have reported greater COVID-19 severity and poorer outcomes, such as ICU (intensive care unit) admissions and deaths among men. An improved understanding of the impact of gender on COVID-19 severity and outcomes could enable tailored management and thereby reduce the global health burden of COVID-19.

About the study

In the present retrospective cohort study, researchers evaluated sex-based differences in managing SARS-CoV-2 infections. The team reviewed data from SARS-CoV-2-positive individuals hospitalized at South Korean tertiary care hospitals between February 2, 2020, and March 31, 2021. Data were retrieved from electronic health records pertaining to demographic characteristics, COVID-19 symptoms prior to hospitalization, and laboratory reports at hospitalization admission.

In addition, the team collected data on medical therapy received, invasive treatments (central line, arterial line, tracheostomy, mechanical ventilator support, CRRT (continuous renal replacement therapy), the DNR (do not resuscitate) file, within-hospital deaths, and hospitalization duration. SOFA (sequential organ failure assessment) scores and CFS (clinical fatigue scale) scores were used for patient evaluation. Multivariate logistic regression modeling was performed, and odds ratios (OR) were calculated for factors increasing the risk of SARS-CoV-2 infection-associated within-hospital deaths.

SARS-CoV-2 infection diagnosis was confirmed via polymerase chain reaction (PCR). Severe SARS-CoV-2 infections were those with SpO₂ (oxygen saturation) below 94.0% at room temperature, a respiratory rate exceeding 30.0 breaths per minute, PaO₂/FiO₂ (partial pressure of oxygen divided by the fraction of inspired oxygen) ratio below 300.0 mm of Hg as determined by arterial blood gas (ABG) analysis, or pulmonary infiltration exceeding 50.0%, as determined by imaging. Critical SARS-CoV-2 infections were those presenting with multi-organ disease, septic shock, or pulmonary failure.

Findings

During the study period, 584 SARS-CoV-2-positive individuals were hospitalized, of which 52% (n=305) were women older than the male participants (58 years versus 55 years). CFS scores were lower among men than women (1.90 versus 2.20). Men more commonly presented with fever and less commonly reported sore throat; however, there were no significant differences in other initially observed clinical symptoms of SARS-CoV-2 infections.

Chronic obstructive pulmonary disease (COPD) was more commonly observed among men than women (3.90% versus 1.30%), with no statistically significant differences in any of the other comorbid conditions. Men presented with greater leukocyte counts, elevated total bilirubin, creatinine, ALT (alanine aminotransferase), and CRP (C-reactive protein).

There were no significant sex-based differences in COVID-19 severity, management, and outcomes. No significant gender-based differences were observed in oxygenation devices (nasal prongs, high-flow nasal cannulas, extracorporeal membrane oxygenation, and invasive mechanical ventilators). Likewise, the choice of medication (such as antibiotics, remdesivir, and steroids) and vasopressor type (vasopressin, dobutamine, or norepinephrine) did not significantly differ between the two groups.

No significant differences in COVID-19 severity (7.0% versus 10%) or critical SARS-CoV-2 infection prevalence (10.0% versus 8.0%) were observed among males versus females. Moreover, no significant differences were observed in the choice of invasive therapy (central line, arterial line, CRRT, or tracheostomy), with no significant differences in within-hospital deaths (3.0% versus 4.0%). Additionally, no gender-based differences were observed in the duration of hospitalization and DNR document filing. Advanced age (odds ratio 1.2), elevated leukocyte counts (odds ratio 1.5), and elevated CRP (C-reactive protein, odds ratio 1.1) levels enhanced the risk of within-hospital death.

Differences in lifestyle habits and immunological responses between females and males have been suggested. Studies have reported that viral immunological responses are stronger in females, with probable differences in the genetic composition of the X  and Y chromosomes, affecting the expression of TMPRSS2 (transmembrane protease serine subtype 2) and ACE2 (angiotensin-converting enzyme 2), critical for SARS-CoV-2 entry into the host.

Drinking and smoking are more prevalent among men and may be associated with comorbid conditions such as cardiovascular diseases, cancer, and COPD. Smoking has also been linked to greater ACE2 expression. However, COVID-19 outcomes did not significantly differ by sex in the study, and further research may be performed further to explore the effects of sex on COVID-19 outcomes.

Based on the study findings, sex does not significantly impact COVID-19 clinical features and outcomes.