Abstract
BackgroundMales and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take the sex factor into consideration.MethodsWe performed a sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and severe acute respiratory syndrome coronavirus (SARS-CoV-2) specific antibody levels of 1558 males and 1499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. The total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence.ResultsWe found that male patients had approximately two-fold rates of ICU admission (4.7% vs. 2.7% in males and females, respectively, P = 0.005) and mortality (3% vs. 1.4%, in males and females, respectively, P = 0.004) than female patients. Survival analysis revealed that the male sex is an independent risk factor for death from COVID-19 (adjusted hazard ratio [HR] = 2.22, 95% confidence interval [CI]: 1.3–3.6, P = 0.003). The level of inflammatory cytokines in peripheral blood was higher in males during hospitalization. The renal (102/1588 [6.5%] vs. 63/1499 [4.2%], in males and females, respectively, P = 0.002) and hepatic abnormality (650/1588 [40.9%] vs. 475/1499 [31.7%], P = 0.003) were more common in male patients than in female patients. By analyzing dynamic changes of lymphocyte subsets after symptom onset, we found that the percentage of CD19+ B cells and CD4+ T cells was generally higher in female patients during the disease course of COVID-19. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in female patients, while gradually increased and reached a peak in the seventh week after symptom onset in male patients.ConclusionsMales had an unfavorable prognosis, higher inflammation, a lower percentage of lymphocytes, and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients.
Highlights
Males and females differ in their immunological responses to foreign pathogens
Sex is an independent prognostic factor for COVID-19 To assess the impact of sex in COVID-19, we compared the clinical characteristics and outcomes between male and female patients (Table 1)
The hospitalization time had no significant difference between sex, the severity of COVID-19 patients was significantly associated with male sex (P = 0.002), with the percentage of critically ill patients higher in male patients than in female patients (6.2% vs. 3.5%, in males and females, respectively)
Summary
Males and females differ in their immunological responses to foreign pathogens. most of the current COVID-19 clinical practices and trials do not take the sex factor into consideration. Epidemiological studies showed that the incidence and mortality of SARS-CoV infection were sexdependent [6]. Males were more susceptible and experienced more severe disease after SARS-CoV infection [7]. Takahashi T et al reported that male COVID-19 patients had higher innate cytokines, lower T cell response, and higher mortality compared with female patients [11]. Some studies reported differences in clinical outcomes between male and female COVID-19 patients, due to insufficient test data samples, a comprehensive analysis of the underlying cellular and molecular mechanisms was not conducted. By describing the clinical and laboratory characteristics of 3057 COVID-19 patients from a single center, we performed a sex-based comparative analysis for the clinical, cellular, and molecular differences in COVID-19. Our results provide important information for the epidemiology and precise therapy for this emergent pandemic
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