Effects of Angiotensin II Receptor Blockers and ACE (Angiotensin-Converting Enzyme) Inhibitors on Virus Infection, Inflammatory Status, and Clinical Outcomes in Patients With COVID-19 and Hypertension

  1. Guang Yang
  2. Zihu Tan
  3. Ling Zhou
  4. Min Yang
  5. Lang Peng
  6. Jinjin Liu
  7. Jingling Cai
  8. Ru Yang
  9. Junyan Han
  10. Yafei Huang
  11. Shaobin He

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Abstract

With the capability of inducing elevated expression of ACE2 (angiotensin-converting enzyme 2), the cellular receptor for severe acute respiratory syndrome coronavirus 2, angiotensin II receptor blockers (ARBs) or ACE inhibitors treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the effects of ARBs/ACE inhibitors on coronavirus disease 2019 (COVID-19) in a retrospective, single-center study. One hundred twenty-six patients with COVID-19 and preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine in Wuhan from January 5 to February 22, 2020, were retrospectively allocated to ARBs/ACE inhibitors group (n=43) and non-ARBs/ACE inhibitors group (n=83) according to their antihypertensive medication. One hundred twenty-five age- and sex-matched patients with COVID-19 without hypertension were randomly selected as nonhypertension controls. In addition, the medication history of 1942 patients with hypertension that were admitted to Hubei Provincial Hospital of Traditional Chinese Medicine from November 1 to December 31, 2019, before the COVID-19 outbreak were also reviewed for external comparison. Epidemiological, demographic, clinical, and laboratory data were collected, analyzed, and compared between these groups. The frequency of ARBs/ACE inhibitors usage in patients with hypertension with or without COVID-19 were comparable. Among patients with COVID-19 and hypertension, those received either ARBs/ACE inhibitors or non-ARBs/ACE inhibitors had comparable blood pressure. However, ARBs/ACE inhibitors group had significantly lower concentrations of hs-CRP (high-sensitivity C-reactive protein; P =0.049) and PCT (procalcitonin, P =0.008). Furthermore, a lower proportion of critical patients (9.3% versus 22.9%; P =0.061) and a lower death rate (4.7% versus 13.3%; P =0.216) were observed in ARBs/ACE inhibitors group than non-ARBs/ACE inhibitors group, although these differences failed to reach statistical significance. Our findings thus support the use of ARBs/ACE inhibitors in patients with COVID-19 and preexisting hypertension.

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  1. Version published to 10.1161/hypertensionaha.120.15143
  2. ScreenIT

    SciScore for 10.1101/2020.03.31.20038935: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Study Design and Participants: This retrospective study complied with the Declaration of Helsinki and was approved by the Hubei Provincial Hospital of Traditional Chinese Medicine (HPHTCM)’s ethical review board (Clinical Ethical Approval No. HBZY2020-C15-01).
    Consent: Written informed consent was waived by the Ethics Commission of the hospital for emerging infectious diseases.
    RandomizationAge- and sex-matched cases were randomly selected from the remaining COVID-19 patients without hypertension as non-hypertension controls.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical Analysis: Data analysis was performed using SPSS (Statistical Package for the Social Sciences, version 23).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    Statistical Package for the Social Sciences
    suggested: (SPSS, RRID:SCR_002865)

    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:
    Our study has several limitations. First, due to the retrospective nature of this study and the fact that it was conducted in a single hospital, interpretation of our findings might be limited by the sample size and selection bias. We also realize that there are additional risk factors may not be well-controlled despite as many confounders as possible were corrected for. Nevertheless, as far as we know, this is the largest retrospective cohort study designed to examine the usage of ARBs/ACEIs and its effect on COVID-19 patients with preexisting hypertension. Second, the severity and disease course were not identical among these patients, which resulted in the difficulty in collecting laboratory indicators at the same time point, we therefore selected the most extreme values beyond the normal range of laboratory indicators that could reflect the severity of condition for comparison. However, this strategy might still cause biases in presenting laboratory indicators. Third, the expression of ACE2 and other inflammatory factors were not determined in this study due to the sample availability and limited technical resources in our hospital, this limitation prevented us from further exploring the mechanisms by which ARBs/ACEIs regulate the inflammatory status of COVID-19 patients with hypertension.

    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 10.1101/2020.03.31.20038935 on medRxiv