Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens.

Tatsuo Shimosawa,Aldo De Togni,Francesca Bravi,Giustino Parruti,Lorenzo Mantovani,Lamberto Manzoli,Tiziano Carradori,Maria Elena Flacco,Carlo Alberto Volta,Giuseppe Cosenza,Cecilia Acuti Martellucci

doi:10.1371/journal.pone.0235248

Tatsuo Shimosawa, Aldo De Togni + Show 9 more

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https://doi.org/10.1371/journal.pone.0235248

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Journal: PloS one	Publication Date: Jun 24, 2020
Citations: 82	License type: CC BY 4.0

Abstract

This retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs). All adults with SARS-CoV-2 infection in two Italian provinces were followed for a median of 24 days. ARBs and/or ACEi treatments, and hypertension, diabetes, cancer, COPD, renal and major cardiovascular diseases (CVD) were extracted from clinical charts and electronic health records, up to two years before infection. The sample consisted of 1603 subjects (mean age 58.0y; 47.3% males): 454 (28.3%) had severe symptoms, 192 (12.0%) very severe or lethal disease (154 deaths; mean age 79.3 years; 70.8% hypertensive, 42.2% with CVD). The youngest deceased person aged 44 years. Among hypertensive subjects (n = 543), the proportion of those treated with ARBs or ACEi were 88.4%, 78.7% and 80.6% among patients with mild, severe and very severe/lethal disease, respectively. At multivariate analysis, no association was observed between therapy and disease severity (Adjusted OR for very severe/lethal COVID-19: 0.87; 95% CI: 0.50-1.49). Significant predictors of severe disease were older age (with AORs largely increasing after 70 years of age), male gender (AOR: 1.76; 1.40-2.23), diabetes (AOR: 1.52; 1.05-2.18), CVD (AOR: 1.88; 1.32-2.70) and COPD (AOR: 1.88; 1.11-3.20). Only gender, age and diabetes also predicted very severe/lethal disease. No association was found between COVID-19 severity and treatment with ARBs and/or ACEi, supporting the recommendation to continue medication for all patients unless otherwise advised by their physicians.

Highlights

Novel coronavirus disease (COVID-19) is spreading worldwide, and has caused over 250,000 deaths so far [1]
No association was found between COVID-19 severity and treatment with angiotensin II type-I receptor blockers (ARBs) and/or Angiotensin-Converting Enzyme inhibitors (ACEi), supporting the recommendation to continue medication for all patients unless otherwise advised by their physicians
Observing that human pathogenic coronaviruses bind their target cells through angiotensin-converting enzyme 2 (ACE2) [5,6,7,8], and that a few studies reported an increase in ACE2 expression mediated by angiotensin II type-I receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors [9,10,11,12,13,14,15,16], some hypothesized that the increased expression of ACE2 would facilitate infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the hypertension treatment with ACE2-stimulating drugs, as well as ACE2 polymorphisms, might increase the risk of developing severe COVID-19 [17,18,19]

Summary

Introduction

Novel coronavirus disease (COVID-19) is spreading worldwide, and has caused over 250,000 deaths so far [1]. Observing that human pathogenic coronaviruses bind their target cells through angiotensin-converting enzyme 2 (ACE2) [5,6,7,8], and that a few studies reported an increase in ACE2 expression mediated by angiotensin II type-I receptor blockers (ARBs) and ACE inhibitors (more consistently on animals than in humans) [9,10,11,12,13,14,15,16], some hypothesized that the increased expression of ACE2 would facilitate infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the hypertension treatment with ACE2-stimulating drugs, as well as ACE2 polymorphisms, might increase the risk of developing severe COVID-19 [17,18,19] This would lead to a serious conflict regarding treatment, because ACE2 reduces inflammation and has been suggested as a potential new therapy for inflammatory lung diseases, cancer, diabetes, and hypertension [17, 20,21,22,23]. We have performed a case-control study on all SARS-CoV-2 infected subjects diagnosed in two Italian provinces, retrieving admission and pharmacological data up to two years before infection, in order to confirm the potential independent predictors of severe/lethal COVID-19, including treatment with ACE inhibitors and/or ARBs

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