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

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

doi:10.3389/fcvm.2021.710946

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

Front Cardiovasc Med. 2021 Aug 19:8:710946. doi: 10.3389/fcvm.2021.710946. eCollection 2021.

Authors

Linna Huang^{1

2

3}, Ziying Chen^{1

2

3

4}, Lan Ni⁵, Lei Chen⁶, Changzhi Zhou⁷, Chang Gao⁸, Xiaojing Wu^{1

2

3}, Lin Hua⁹, Xu Huang^{1

2

3}, Xiaoyang Cui^{1

2

3}, Ye Tian^{1

2

3}, Zeyu Zhang^{1

2

3}, Qingyuan Zhan^{1

2

3}

Affiliations

¹ Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.
² Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China.
³ National Clinical Research Center for Respiratory Diseases, Beijing, China.
⁴ Peking University Health Science Center, Beijing, China.
⁵ Department of Pulmonary and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
⁶ Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁷ Department of Pulmonary and Critical Care Medicine, The Central Hospital of Wuhan, Wuhan, China.
⁸ Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
⁹ School of Biomedical Engineering, Capital Medical University, Beijing, China.

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.

Keywords: ACE inhibitor; ARB; COVID-19; inflammatory response; viral clearance.