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

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

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)(*)10(9)/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 Since the limited influence on the ACEI/ARB treatment, they should not be withdrawn if there was no formal contraindication.