Angiotensin‐converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID‐19 infection in a multi‐site UK acute hospital trust

  1. Daniel M. Bean
  2. Zeljko Kraljevic
  3. Thomas Searle
  4. Rebecca Bendayan
  5. O'Gallagher Kevin
  6. Andrew Pickles
  7. Amos Folarin
  8. Lukasz Roguski
  9. Kawsar Noor
  10. Anthony Shek
  11. Rosita Zakeri
  12. Ajay M. Shah
  13. James T.H. Teo
  14. Richard J.B. Dobson

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Abstract

Aims

The SARS‐CoV‐2 virus binds to the angiotensin‐converting enzyme 2 (ACE2) receptor for cell entry. It has been suggested that angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID‐19 infection.

Methods and results

We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID‐19 at two hospitals with a multi‐ethnic catchment population in London (UK). The mean age was 68 ± 17 years (57% male) and 74% of patients had at least one comorbidity. Overall, 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21 days of symptom onset. A total of 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co‐morbidities, was 0.63 (95% confidence interval 0.47–0.84, P  < 0.01).

Conclusions

There was no evidence for increased severity of COVID‐19 in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta‐analyses and randomised clinical trials.

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  1. ScreenIT

    SciScore for 10.1101/2020.04.07.20056788: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This project operated under London South East Research Ethics Committee approval (reference 18/LO/2048) granted to the King’s Electronic Records Research Interface (KERRI); specific work on COVID19 research was reviewed with expert patient input on a virtual committee with Caldicott Guardian oversight.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The performance of DrugPipeline has previously been described.
    DrugPipeline
    suggested: None

    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 some potential limitations. Although the patients and data were prospectively collected, the analyses were retrospective. The study was conducted on two hospital sites in a single geographical, albeit ethnically mixed, locus in the UK over a relatively short follow-up period. However, the duration of follow-up is sufficient to accurately detect early severe outcomes based on the data from multiple studies during the current pandemic. We used the covariates identified as important in the previous large case series on COVID19 1–3, including age, sex and common comorbidities, to adjust our analyses. However, it is possible that other unmeasured confounders could have influenced the results. For example, the patients on chronic ACEi/ARB treatment were also more frequently treated with statins than those not on these drugs, which could suggest that their medical conditions were generally better managed. However, the ACEi/ARB group was also older and had higher rates of hypertension, diabetes and multiple morbidities, making it unlikely that these patients were physiologically healthier. Our study was performed in patients with COVID19 who required hospitalisation; the effect of chronic treatment with ACEi/ARB on less severe infection with SARS-CoV2 in the non-hospital setting requires further study. Whether the current results are applicable to other global populations, such as in Africa, will also require additional study. In summary, the results of this study in 12...

    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 10.1002/ejhf.1924
  3. Version published to 10.1101/2020.04.07.20056788v2 on medRxiv
  4. Version published to 10.1101/2020.04.07.20056788v1 on medRxiv