Sex and Gender Differences in Testing, Hospital Admission, Clinical Presentation, and Drivers of Severe Outcomes From COVID-19

  1. Eileen P Scully
  2. Grant Schumock
  3. Martina Fu
  4. Guido Massaccesi
  5. John Muschelli
  6. Joshua Betz
  7. Eili Y Klein
  8. Natalie E West
  9. Matthew Robinson
  10. Brian T Garibaldi
  11. Karen Bandeen-Roche
  12. Scott Zeger
  13. Sabra L Klein
  14. Amita Gupta

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Abstract

Background

Males experience increased severity of illness and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with females, but the mechanisms of male susceptibility are unclear.

Methods

We performed a retrospective cohort analysis of SARS-CoV-2 testing and admission data at 5 hospitals in the Maryland/Washington DC area. Using age-stratified logistic regression models, we quantified the impact of male sex on the risk of the composite outcome of severe disease or death (World Health Organization score 5–8) and tested the impact of demographics, comorbidities, health behaviors, and laboratory inflammatory markers on the sex effect.

Results

Among 213 175 SARS-CoV-2 tests, despite similar positivity rates, males in age strata between 18 and 74 years were more frequently hospitalized. For the 2626 hospitalized individuals, clinical inflammatory markers (interleukin-6, C-reactive protein, ferritin, absolute lymphocyte count, and neutrophil:lymphocyte ratio) were more favorable for females than males (P < .001). Among 18–49-year-olds, male sex carried a higher risk of severe outcomes, both early (odds ratio [OR], 3.01; 95% CI, 1.75 to 5.18) and at peak illness during hospitalization (OR, 2.58; 95% CI, 1.78 to 3.74). Despite multiple differences in demographics, presentation features, comorbidities, and health behaviors, these variables did not change the association of male sex with severe disease. Only clinical inflammatory marker values modified the sex effect, reducing the OR for severe outcomes in males aged 18–49 years to 1.81 (95% CI, 1.00 to 3.26) early and 1.39 (95% CI, 0.93 to 2.08) at peak illness.

Conclusions

Higher inflammatory laboratory test values were associated with increased risk of severe coronavirus disease 2019 for males. A sex-specific inflammatory response to SARS-CoV-2 infection may underlie the sex differences in outcomes.

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  1. Version published to 10.1093/ofid/ofab448
  2. ScreenIT

    SciScore for 10.1101/2021.04.05.21253827: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The institutional review boards of these hospitals approved this study as minimal risk and waived consent requirements.
    Consent: The institutional review boards of these hospitals approved this study as minimal risk and waived consent requirements.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableWe identified individuals with an SpO2:FiO2 (oxygen saturation:fraction of inspired oxygen) ratio of <256 as qualified for tocilizumab and determined total numbers of females and males who had qualifying values at any point during hospitalization.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The study design and inclusion criteria for sequentially admitted patients with SARS-CoV-2 have been in part been described elsewhere29.
    SARS-CoV-2
    suggested: (Active Motif Cat# 91351, RRID:AB_2847848)

    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.

  3. Version published to 10.1101/2021.04.05.21253827v1 on medRxiv