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. 2021 Jul 5;21(1):647.
doi: 10.1186/s12879-021-06313-2.

Sex-based clinical and immunological differences in COVID-19

Bin Huang #  1   2   3 , Yun Cai #  1   2 , Ning Li #  1   2 , Kening Li #  1   2 , Zhihua Wang  4   5 , Lu Li  1   2 , Lingxiang Wu  1   2 , Mengyan Zhu  1   2 , Jie Li  1   2 , Ziyu Wang  1   2 , Min Wu  1   2 , Wanlin Li  1   2 , Wei Wu  1   2 , Lishen Zhang  1   2   3 , Xinyi Xia  6   7 , Shukui Wang  8 , Hongshan Chen  9   10   11 , Qianghu Wang  12   13   14
Affiliations

Sex-based clinical and immunological differences in COVID-19

Bin Huang et al. BMC Infect Dis. .

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.

Keywords: COVID-19; Immunology; Prognosis; SARS-CoV-2; Sex.

PubMed Disclaimer

Conflict of interest statement

We declare no competing interests.

Figures

Fig. 1
Fig. 1
Survival analysis and comparison of prognostic related indicators between males and females from the first to 11th week after symptom onset. A Sex-based survival analysis of COVID-19 patients. B-E Differences of laboratory findings in male and female patients. Red represents female patients, and blue represents male patients. The x-axis displays weeks after symptom onset. The y-axis displays the level of indicators or percentage of patients with abnormal indicators. The line chart shows the mean and standard deviation of indicator values, and the significance is calculated by the Wilcoxon test. The Fisher test calculates the significance in the histogram. The number of patients per week after symptom onset is shown in the graph. *, P < 0.05; **, P < 0.01; ***, P < 0.001
Fig. 2
Fig. 2
Comparison of lymphocyte subsets in peripheral blood between males and females from the first to 11th week after symptom onset. Red represents female patients, and blue represents male patients. The x-axis displays weeks after symptom onset. The y-axis displays the level of indicators or percentage of patients with abnormal indicators. The line chart shows the mean and standard deviation of indicator values. The line chart shows the mean and standard deviation of indicator values, and the significance is calculated by the Wilcoxon test. The Fisher test calculates the significance in the histogram. The number of patients per week after symptom onset is shown in the graph. *, P < 0.05; **, P < 0.01; ***, P < 0.001
Fig. 3
Fig. 3
The dynamic changes of antibodies against SARS-CoV-2. The x-axis displays the weeks after symptom onset. The numbers below the figure represent the number of tests of females and males. The y-axis displays the level of IgG level. The red line based on the median is used to profile the females’ variation tendency, and the blue line based on the median is used to profile the males’ variation tendency. The significance is calculated by the Wilcoxon rank-sum test. The number of patient tests per week after symptom onset is shown in the graph. *, P < 0.05; **, P < 0.01; ***, P < 0.001
See this image and copyright information in PMC

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