Impact of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on the Inflammatory Response and Viral Clearance in COVID-19 Patients.

Linna Huang,Zeyu Zhang,Lan Ni,Xiaojing Wu,Lin Hua,Xiaoyang Cui,Xu Huang,Changzhi Zhou,Ziying Chen,Lei Chen,Qingyuan Zhan,Ye Tian,Chang Gao

doi:10.3389/fcvm.2021.710946

Abstract

Objectives: To evaluate the impact of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) on the inflammatory response and viral clearance in coronavirus disease 2019 (COVID-19) patients.Methods: We included 229 patients with confirmed COVID-19 in a multicenter, retrospective cohort study. Propensity score matching at a ratio of 1:3 was introduced to eliminate potential confounders. Patients were assigned to the ACEI/ARB group (n = 38) or control group (n = 114) according to whether they were current users of medication.Results: Compared to the control group, patients in the ACEI/ARB group had lower levels of plasma IL-1β [(6.20 ± 0.38) vs. (9.30 ± 0.31) pg/ml, P = 0.020], IL-6 [(31.86 ± 4.07) vs. (48.47 ± 3.11) pg/ml, P = 0.041], IL-8 [(34.66 ± 1.90) vs. (47.93 ± 1.21) pg/ml, P = 0.027], and TNF-α [(6.11 ± 0.88) vs. (12.73 ± 0.26) pg/ml, P < 0.01]. Current users of ACEIs/ARBs seemed to have a higher rate of vasoconstrictive agents (20 vs. 6%, P < 0.01) than the control group. Decreased lymphocyte counts [(0.76 ± 0.31) vs. (1.01 ± 0.45)*109/L, P = 0.027] and elevated plasma levels of IL-10 [(9.91 ± 0.42) vs. (5.26 ± 0.21) pg/ml, P = 0.012] were also important discoveries in the ACEI/ARB group. Patients in the ACEI/ARB group had a prolonged duration of viral shedding [(24 ± 5) vs. (18 ± 5) days, P = 0.034] and increased length of hospitalization [(24 ± 11) vs. (15 ± 7) days, P < 0.01]. These trends were similar in patients with hypertension.Conclusions: Our findings did not provide evidence for a significant association between ACEI/ARB treatment and COVID-19 mortality. ACEIs/ARBs might decrease proinflammatory cytokines, but antiviral treatment should be enforced, and hemodynamics should be monitored closely. Since the limited influence on the ACEI/ARB treatment, they should not be withdrawn if there was no formal contraindication.

Highlights

Up to March 31, 2020, the total number of patients with coronavirus disease 2019 has risen sharply to nearly 700,000 globally, with a mortality rate of nearly 5%
Angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) have an impact on the reninangiotensin system (RAS) and are postulated to attenuate pulmonary and systemic inflammatory responses, reducing the severity and mortality of viral pneumonia-related acute respiratory distress syndrome [6,7,8], by angiotensinconverting enzyme 2 (ACE2) upregulation through the ACE2Ang-(1-7)-Mas axis [9]
The expression of ACE2 is substantially increased in patients who are treated with ACE inhibitors and ARBs [12], which promotes SARS-CoV-2 entry into the body, increasing the risk of developing COVID-19 [13, 14]

Summary

Introduction

Up to March 31, 2020, the total number of patients with coronavirus disease 2019 has risen sharply to nearly 700,000 globally, with a mortality rate of nearly 5%. This epidemic seems to be spreading at an exponential rate and has become an urgent public health emergency of international concern. ACEIs/ARBs have an impact on the reninangiotensin system (RAS) and are postulated to attenuate pulmonary and systemic inflammatory responses, reducing the severity and mortality of viral pneumonia-related acute respiratory distress syndrome [6,7,8], by angiotensinconverting enzyme 2 (ACE2) upregulation through the ACE2Ang-(1-7)-Mas axis [9]. The expression of ACE2 is substantially increased in patients who are treated with ACE inhibitors and ARBs [12], which promotes SARS-CoV-2 entry into the body, increasing the risk of developing COVID-19 [13, 14]

Objectives

Methods

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Conclusion