Treatment with ACE-inhibitors is associated with less severe disease with SARS-Covid-19 infection in a multi-site UK acute Hospital Trust

Abstract: Background: The SARS-Cov2 virus binds to the ACE2 receptor for cell entry. It has been suggested that ACE-inhibitors, which are commonly used in patients with hypertension or diabetes and which raise ACE2 levels, may increase the risk of severe COVID-19 infection. Methods: We evaluated this hypothesis in an early cohort of 205 acute inpatients with COVID-19 at King's College Hospital and Princess Royal University Hospital, London, UK with the primary endpoint being death or transfer to a critical care unit for organ support within 7-days of symptom onset. Findings: 53 patients out of 205 patients reached the primary endpoint. Contrary to the hypothesis, treatment with ACE-inhibitors was associated with a reduced risk of rapidly deteriorating severe disease. There was a lower rate of death or transfer to a critical care unit within 7 days in patients on an ACE-inhibitor OR 0.29 (CI 0.10-0.75, p<0.01), adjusting for age, gender, comorbidities (hypertension, diabetes mellitus, ischaemic heart disease and heart failure). Interpretation: Although a small sample size, we do not see evidence for ACE-inhibitors increasing the short-term severity of COVID-19 disease and patients on treatment with ACE-inhibitors should continue these drugs during their COVID-19 illness. A potential beneficial effect needs to be explored as more data becomes available.

[1]  Y. Hu,et al.  [Asymptomatic infection of COVID-19 and its challenge to epidemic prevention and control]. , 2020, Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi.

[2]  G. Onder,et al.  Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. , 2020, JAMA.

[3]  O. Pfister,et al.  SARS-CoV2: should inhibitors of the renin–angiotensin system be withdrawn in patients with COVID-19? , 2020, European heart journal.

[4]  Michael Roth,et al.  Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? , 2020, The Lancet Respiratory Medicine.

[5]  G. Herrler,et al.  SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor , 2020, Cell.

[6]  Maya B. Mathur,et al.  Conducting sensitivity analysis for unmeasured confounding in observational studies using E-values: The evalue package , 2020 .

[7]  J. Xiang,et al.  Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study , 2020, The Lancet.

[8]  John Watkins,et al.  Preventing a covid-19 pandemic , 2020, BMJ.

[9]  Richard Dobson,et al.  MedCAT - Medical Concept Annotation Tool , 2019, ArXiv.

[10]  R. Dobson,et al.  Semantic computational analysis of anticoagulation use in atrial fibrillation from real world data , 2019, PloS one.

[11]  Thomas Searle,et al.  MedCATTrainer: A Biomedical Free Text Annotation Interface with Active Learning and Research Use Case Specific Customisation , 2019, EMNLP.

[12]  Marta Avalos,et al.  Penalized logistic regression with low prevalence exposures beyond high dimensional settings , 2019, PloS one.

[13]  Tudor Groza,et al.  CogStack - experiences of deploying integrated information retrieval and extraction services in a large National Health Service Foundation Trust hospital , 2017, bioRxiv.

[14]  Peter Szolovits,et al.  MIMIC-III, a freely accessible critical care database , 2016, Scientific Data.

[15]  Xuefeng Wang,et al.  Firth logistic regression for rare variant association tests , 2014, Front. Genet..

[16]  Mark Chappell,et al.  A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury , 2005, Nature Medicine.

[17]  Arthur S Slutsky,et al.  Angiotensin-converting enzyme 2 protects from severe acute lung failure , 2005, Nature.

[18]  D. Firth Bias reduction of maximum likelihood estimates , 1993 .