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Sex-based clinical and immunological differences in COVID-19

By Kening Li, Bin Huang, Yun Cai, Zhihua Wang, Lu Li, Lingxiang Wu, Mengyan Zhu, Jie Li, Ziyu Wang, Min Wu, Wanlin Li, Wei Wu, Lishen Zhang, Xinyi Xia, Shukui Wang, Qianghu Wang

Posted 01 Sep 2020
medRxiv DOI: 10.1101/2020.08.29.20126201

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 IgG 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. Hormonal or convalescent plasma therapy may help improve the immunity of males to fight against SARS-CoV-2 infection.

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