Sex-specificity of mortality risk factors among hospitalized COVID-19 patients in New York City: prospective cohort study

  1. Tomi Jun
  2. Sharon Nirenberg
  3. Patricia Kovatch
  4. Kuan-lin Huang

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Abstract

Objective

To identify sex-specific effects of risk factors for in-hospital mortality among COVID-19 patients admitted to a hospital system in New York City.

Design

Prospective observational cohort study with in-hospital mortality as the primary outcome.

Setting

Five acute care hospitals within a single academic medical system in New York City.

Participants

3,086 hospital inpatients with COVID-19 admitted on or before April 13, 2020 and followed through June 2, 2020. Follow-up till discharge or death was complete for 99.3% of the cohort.

Results

The majority of the cohort was male (59.6%). Men were younger (median 64 vs. 70, p<0.001) and less likely to have comorbidities such as hypertension (32.5% vs. 39.9%, p<0.001), diabetes (22.6% vs. 26%, p=0.03), and obesity (6.9% vs. 9.8%, p=0.004) compared to women. Women had lower median values of laboratory markers associated with inflammation compared to men: white blood cells (5.95 vs. 6.8 K/uL, p<0.001), procalcitonin (0.14 vs 0.21 ng/mL, p<0.001), lactate dehydrogenase (375 vs. 428 U/L, p<0.001), C-reactive protein (87.7 vs. 123.2 mg/L, p<0.001). Unadjusted mortality was similar between men and women (28.8% vs. 28.5%, p=0.84), but more men required intensive care than women (25.2% vs. 19%, p<0.001). Male sex was an independent risk factor for mortality (OR 1.26, 95% 1.04-1.51) after adjustment for demographics, comorbidities, and baseline hypoxia. There were significant interactions between sex and coronary artery disease (p=0.038), obesity (p=0.01), baseline hypoxia (p<0.001), ferritin (p=0.002), lactate dehydrogenase (p=0.003), and procalcitonin (p=0.03). Except for procalcitonin, which had the opposite association, each of these factors was associated with disproportionately higher mortality among women.

Conclusions

Male sex was an independent predictor of mortality, consistent with prior studies. Notably, there were significant sex-specific interactions which indicated a disproportionate increase in mortality among women with coronary artery disease, obesity, and hypoxia. These new findings highlight patient subgroups for further study and help explain the recognized sex differences in COVID-19 outcomes.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.29.20164640: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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: We detected the following sentences addressing limitations in the study:
    This study has several limitations. Our analyses are hypothesis-generating and require confirmation in other large cohorts as well as causal studies to establish mechanisms. Comorbidity data was automatically extracted from the electronic medical record and may be incomplete or inaccurate. This cohort reflects patients seen in the Spring of 2020 leading up to and during the initial surge of cases in New York City. Demographics and outcomes of COVID-19 patients may shift over the course of the pandemic. In conclusion, the findings of this large study highlight novel interactions between sex, comorbidities, hypoxia, and markers of inflammation. These interactions nominate patient subgroups for further study and provide insights that may explain the recognized sex differences in outcomes of this disease.

    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.

  2. Version published to 10.1101/2020.07.29.20164640v1 on medRxiv