Association between comorbidities and the risk of death in patients with COVID-19: sex-specific differences

  1. Mingyang Wu
  2. Shuqiong Huang
  3. Jun Liu
  4. Yanling Shu
  5. Yinbo Luo
  6. Lulin Wang
  7. Mingyan Li
  8. Youjie Wang

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Abstract

Background

The coronavirus disease 2019 (Covid-19) spreads rapidly around the world.

Objective

To evaluate the association between comorbidities and the risk of death in patients with COVID-19, and to further explore potential sex-specific differences.

Methods

We analyzed the data from 18,465 laboratory-confirmed cases that completed an epidemiological investigation in Hubei Province as of February 27, 2020. Information on death was obtained from the Infectious Disease Information System. The Cox proportional hazards model was used to estimate the association between comorbidities and the risk of death in patients with COVID-19.

Results

The median age for COVID-19 patients was 50.5 years. 8828(47.81%) patients were females. Severe cases accounted for 20.11% of the study population. As of March 7, 2020, a total of 919 cases deceased from COVID-19 for a fatality rate of 4.98%. Hypertension (13.87%), diabetes (5.53%), and cardiovascular and cerebrovascular diseases (CBVDs) (4.45%) were the most prevalent comorbidities, and 27.37% of patients with COVID-19 reported having at least one comorbidity. After adjustment for age, gender, address, and clinical severity, patients with hypertension (HR 1.55, 95%CI 1.35-1.78), diabetes (HR 1.35, 95%CI 1.13-1.62), CBVDs (HR 1.70, 95%CI 1.43-2.02), chronic kidney diseases (HR 2.09, 95%CI 1.47-2.98), and at least two comorbidities (HR 1.84, 95%CI 1.55-2.18) had significant increased risks of death. And the association between diabetes and the risk of death from COVID-19 was prominent in women (HR 1.69, 95%CI 1.27-2.25) than in men (HR 1.16, 95%CI 0.91-1.46) ( P for interaction = 0.036).

Conclusion

Among laboratory-confirmed cases of COVID-19 in Hubei province, China, patients with hypertension, diabetes, CBVDs, chronic kidney diseases were significantly associated with increased risk of death. The association between diabetes and the risk of death tended to be stronger in women than in men. Clinicians should increase their awareness of the increased risk of death in COVID-19 patients with comorbidities.

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    SciScore for 10.1101/2020.05.22.20109579: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: 9 Waiver of informed consent for collection of epidemiological data from patients with COVID-19 was granted by the National Health Commission of China as part of the infectious disease outbreak investigation.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableAnd covariates included in the Cox model were based on prior publication, including age (20-29, 30-39, 40-49, 50-59, or ≥60 years), gender (women or men), address (Wuhan or not), and clinical severity (severe or not).

    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:
    Nonetheless, a major limitation of these researches has been small sample size. Additionally, sex-specific mortality of SARS-Cov-2 infection has been well elucidated, but no studies have pointed out the sex-specific differences on the correlation of comorbidities with mortality. The present study has therefore added further evidence that comorbidities were associated with a greater mortality in patients with COVID-19 based on the large sample size. The etiology behind the increased risk of death in COVID-19 patients with comorbidities is likely to be multifactorial. Evidence has pointed out that SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as a cell entry receptor.14,15 Recent findings have demonstrated that the SARS-CoV-2 cell receptor gene ACE2 was expressed in a wide variety of human tissues, such as small intestine, kidneys, heart, lungs, and adipose tissue.16 Therefore, the coronavirus may enter various human cells via ACE2-dependent pathway and cause functional deterioration, leading to the exacerbation of the original comorbidities and subsequently increasing the risk of death. Additionally, cells infected by SARS-CoV-2 produce elevated levels of pro-inflammatory cytokines which may cause immuno-mediated damage to the lungs and other organs, resulting in multi-organ dysfunction.11,17,18 Findings from experimental study have illustrated that diabetic mice had a prolonged phase of severe disease and delayed recovery after infection with MERS-CoV.19 Therefore, i...

    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

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  2. Version published to 10.1101/2020.05.22.20109579v1 on medRxiv