Renin-angiotensin system blockers and mortality in COVID-19: a territory-wide study from Hong Kong

  1. Jiandong Zhou
  2. Gary Tse
  3. Sharen Lee
  4. Wing Tak Wong
  5. Xingsong Wang
  6. William KK Wu
  7. Tong Liu
  8. Zhidong Cao
  9. Daniel Dajun Zeng
  10. Ian Chi Kei Wong
  11. Bernard Man Yung Cheung
  12. Qingpeng Zhang

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Abstract

Aims

Renin–angiotensin system blockers such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of adverse outcomes in COVID-19. In this study, the relationships between ACEI/ARB use and COVID-19 related mortality were examined.

Methods

Consecutive patients diagnosed with COVID-19 by RT-PCR at the Hong Kong Hospital Authority between 1 st January and 28 th July 2020 were included.

Results

This study included 2774 patients. The mortality rate of the COVID-19 positive group was 1.5% (n=42). Those who died had a higher median age (82.3[76.5-89.5] vs. 42.9[28.2-59.5] years old; P<0.0001), more likely to have baseline comorbidities of cardiovascular disease, diabetes mellitus, hypertension, and chronic kidney disease (P<0.0001). They were more frequently prescribed ACEI/ARBs at baseline, and steroids, lopinavir/ritonavir, ribavirin and hydroxychloroquine during admission (P<0.0001). They also had a higher white cell count, higher neutrophil count, lower platelet count, prolonged prothrombin time and activated partial thromboplastin time, higher D-dimer, troponin, lactate dehydrogenase, creatinine, alanine transaminase, aspartate transaminase and alkaline phosphatase (P<0.0001). Multivariate Cox regression showed that age, cardiovascular disease, renal disease, diabetes mellitus, the use of ACEIs/ARBs and diuretics, and various laboratory tests remained significant predictors of mortality.

Conclusions

We report that an association between ACEIs/ARBs with COVID-19 related mortality even after adjusting for cardiovascular and other comorbidities, as well as medication use. Patients with greater comorbidity burden and laboratory markers reflecting deranged clotting, renal and liver function, and increased tissue inflammation, and ACEI/ARB use have a higher mortality risk.

Key Points

  • We report that an association between ACEIs/ARBs with COVID-19 related mortality even after adjusting for cardiovascular and other comorbidities, as well as medication use.

  • Patients with greater comorbidity burden and laboratory markers reflecting deranged clotting, renal and liver function, and increased tissue inflammation, and ACEI/ARB use have a higher mortality risk.

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  1. ScreenIT

    SciScore for 10.1101/2020.12.21.20248645: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Study design and population: This study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analyses were performed using RStudio software (Version: 1.1.456) and Python (Version: 3.6).
    RStudio
    suggested: (RStudio, RRID:SCR_000432)
    Python
    suggested: (IPython, RRID:SCR_001658)

    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.

  2. Version published to 10.1101/2020.12.21.20248645 on medRxiv