Sex-based clinical and immunological differences in COVID-19

Authors：Huang, Bin; Cai, Yun; Li, Ning; Li, Kening; Wang, Zhihua; Li, Lu; Wu, Lingxiang; Zhu, Mengyan; Li, Jie; Wang, Ziyu; Wu, Min; Li, Wanlin; Wu, Wei; Zhang, Lishen; Xia, Xinyi; Wang, Shukui^*; Chen, Hongshan^*; Wang, Qianghu^*

Source：BMC INFECTIOUS DISEASES, 2021, 21(1): 647.

DOI：10.1186/s12879-021-06313-2

• COVID-19
• Sex
• Immunology
• Prognosis
• SARS-CoV-2

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.

• Institution
  1; 南方医科大学; 南京大学