Positive association of angiotensin II receptor blockers, not angiotensin-converting enzyme inhibitors, with an increased vulnerability to SARS-CoV-2 infection in patients hospitalized for suspected COVID-19 pneumonia

  1. Jean-Louis Georges
  2. Floriane Gilles
  3. Hélène Cochet
  4. Alisson Bertrand
  5. Marie De Tournemire
  6. Victorien Monguillon
  7. Maeva Pasqualini
  8. Alix Prevot
  9. Guillaume Roger
  10. Joseph Saba
  11. Joséphine Soltani
  12. Mehrsa Koukabi-Fradelizi
  13. Jean-Paul Beressi
  14. Cécile Laureana
  15. Jean-François Prost
  16. Bernard Livarek

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Abstract

Angiotensin-converting enzyme 2 is the receptor that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses for entry into lung cells. Because ACE-2 may be modulated by angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), there is concern that patients treated with ACEIs and ARBs are at higher risk of coronavirus disease 2019 (COVID-19) pneumonia.

Aim

This study sought to analyze the association of COVID-19 pneumonia with previous treatment with ACEIs and ARBs.

Materials and methods

We retrospectively reviewed 684 consecutive patients hospitalized for suspected COVID-19 pneumonia and tested by polymerase chain reaction assay. Patients were split into two groups, according to whether (group 1, n = 484) or not (group 2, n = 250) COVID-19 was confirmed. Multivariable adjusted comparisons included a propensity score analysis.

Results

The mean age was 63.6 ± 18.7 years, and 302 patients (44%) were female. Hypertension was present in 42.6% and 38.4% of patients in groups 1 and 2, respectively (P = 0.28). Treatment with ARBs was more frequent in group 1 than group 2 (20.7% vs. 12.0%, respectively; odds ratio [OR] 1.92, 95% confidence interval [CI] 1.23–2.98; P = 0.004). No difference was found for treatment with ACEIs (12.7% vs. 15.7%, respectively; OR 0.81, 95% CI 0.52–1.26; P = 0.35). Propensity score-matched multivariable logistic regression confirmed a significant association between COVID-19 and previous treatment with ARBs (adjusted OR 2.36, 95% CI 1.38–4.04; P = 0.002). Significant interaction between ARBs and ACEIs for the risk of COVID-19 was observed in patients aged > 60 years, women, and hypertensive patients.

Conclusions

This study suggests that ACEIs and ARBs are not similarly associated with COVID-19. In this retrospective series, patients with COVID-19 pneumonia more frequently had previous treatment with ARBs compared with patients without COVID-19.

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  1. Version published to 10.1371/journal.pone.0244349
  2. ScreenIT

    SciScore for 10.1101/2020.08.30.20182451: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Patients and/or legal representatives received informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All statistical analyses were carried out with the SPSS® version 19.0 software (SPSS Inc., Chicago, IL) and the R version i386 3.6.2.software.
    SPSS
    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:
    Study Limitations: This study has several limitations. Although it was prospectively designed, collection and analyses of data were retrospective. The biases classically associated with retrospective studies may account for the observed differences. Particularly, a misclassification of patients with and without COVID-19 may have occurred. In case of discrepancy between typical clinical symptoms/chest CT scan abnormalities and a first negative RT-PCR in swab, routine practice was to perform a second PCR in sputum sample, as appropriate, and reach a final collegial diagnosis with clinicians and radiologists if the second PCR was negative. In our study 38/384 of patients of group 1 were diagnosed having probable COVID-19 despite negative PCR. This corresponds to an overall RT-PCR false negative rate of 10%, much lower than the 30% false negative rate reported in Wuhan, China (28). Conversely, few patients who tested negative for PCR were classified as “no COVID-19”, although abnormalities in chest CT scan were consistent with COVID-19. Most of these latter patients had non typical symptoms and an alternative diagnosis (pulmonary infection complicated congestive heart failure or chronic pulmonary disease). Nevertheless, in order to take into account and overcome this putative bias, additional analyses were done excluding the 38 patients with probable COVID-19 (Supplementary Table 3), and then pooling the probable COVID-19 with the non-COVID-19 patients (Supplementary Table 4). Si...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04374695Not yet recruitingRenin-Angiotensin-Aldosterone System Inhibitors, Hypertensio…

    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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  3. Version published to 10.1101/2020.08.30.20182451v1 on medRxiv