Bin Huang1,2,3, Yun Cai1,2, Ning Li1,2, Kening Li1,2, Zhihua Wang4,5, Lu Li1,2, Lingxiang Wu1,2, Mengyan Zhu1,2, Jie Li1,2, Ziyu Wang1,2, Min Wu1,2, Wanlin Li1,2, Wei Wu1,2, Lishen Zhang1,2,3, Xinyi Xia6,7, Shukui Wang8, Hongshan Chen9,10,11, Qianghu Wang12,13,14. 1. Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. 2. Department of Bioinformatics, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. 3. Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China. 4. Department of Laboratory Medicine & Blood Transfusion, the 907th Hospital, Nanping, 350702, Fujian, China. 5. Joint Expert Group for COVID-19, Department of Laboratory Medicine & Blood Transfusion, Wuhan Huoshenshan Hospital, Wuhan, 430100, China. 6. Joint Expert Group for COVID-19, Department of Laboratory Medicine & Blood Transfusion, Wuhan Huoshenshan Hospital, Wuhan, 430100, China. xiaxynju@163.com. 7. COVID-19 Research Center, Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing Clinical College of Southern Medical University, Nanjing, 210002, Jiangsu, China. xiaxynju@163.com. 8. Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China. sk_wang@njmu.edu.cn. 9. Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China. hongshanchen@njmu.edu.cn. 10. Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. hongshanchen@njmu.edu.cn. 11. Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China. hongshanchen@njmu.edu.cn. 12. Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. wangqh@njmu.edu.cn. 13. Department of Bioinformatics, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. wangqh@njmu.edu.cn. 14. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166, China. wangqh@njmu.edu.cn.
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 the sex factor into consideration. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: Males 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.
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 the sex factor into consideration. METHODS: We 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-19patients 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. RESULTS: We 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. CONCLUSIONS: Males 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-19patients.
Entities:
Keywords:
COVID-19; Immunology; Prognosis; SARS-CoV-2; Sex
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