Sex-based clinical and immunological differences in COVID-19 (preprint)

ABSTRACT

Background Males and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take sex as consideration.Methods We performed an unbiased sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and SARS-CoV-2 specific antibody levels of 1,558 males and 1,499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. Total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence.Results We found that the mortality and ICU admission rates were approximately 2-fold higher in males than that in females (P < 0.005). Survival analysis revealed that sex is an independent prognostic factor for COVID-19 (Hazard ratio = 2.2, P = 0.003). The concentration of inflammatory factors in peripheral blood was significantly higher in males. Besides, the renal and hepatic abnormality induced by COVID-19 was more common in males during the hospitalization. The analysis of lymphocyte subsets revealed that the percentage of CD19 + B cell and CD4 + T cell was significantly higher in females (P < 0.001) during hospitalization, indicating the stronger humoral immunity in females than males. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in females, while gradually increased and reached a peak in the seventh week in males.Conclusions The unfavorable prognosis of male COVID-19 patients may result from the weak humoral immunity 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. Convalescent plasma therapy may help improve the immunity of males to fight against SARS-CoV-2 infection.