Sex-based clinical and immunological differences in COVID-19

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

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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.

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  1. Version published to 10.1186/s12879-021-06313-2
  2. Version published to 10.21203/rs.3.rs-78158/v1 on Research Square
  3. ScreenIT

    SciScore for 10.1101/2020.08.29.20126201: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the Medical Ethical Committee of Wuhan Huoshenshan Hospital.
    Consent: Written informed consent was obtained from each patient.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serum anti-SARS-CoV-2 antibodies assay: Total SARS-CoV-2 IgM or IgG in the serum was measured by chemiluminescence using commercially available kits (Shenzhen YHLO Biotech Co., Ltd.), which was coated with N and S proteins, in 1850 patients at different time points.
    anti-SARS-CoV-2
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.08.29.20126201v1 on medRxiv