In coronavirus disease 2019 (COVID-19), hypertension and cardiovascular diseases are major risk factors for critical disease progression. However, the underlying causes and the effects of the main anti-hypertensive therapies—angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)—remain unclear. Combining clinical data (n = 144) and single-cell sequencing data of airway samples (n = 48) with in vitro experiments, we observed a distinct inflammatory predisposition of immune cells in patients with hypertension that correlated with critical COVID-19 progression. ACEI treatment was associated with dampened COVID-19-related hyperinflammation and with increased cell intrinsic antiviral responses, whereas ARB treatment related to enhanced epithelial–immune cell interactions. Macrophages and neutrophils of patients with hypertension, in particular under ARB treatment, exhibited higher expression of the pro-inflammatory cytokines CCL3 and CCL4 and the chemokine receptor CCR1. Although the limited size of our cohort does not allow us to establish clinical efficacy, our data suggest that the clinical benefits of ACEI treatment in patients with COVID-19 who have hypertension warrant further investigation.

在 2019 冠状病毒病 (COVID-19) 中，高血压和心血管疾病是危重病进展的主要危险因素。然而，主要抗高血压疗法——血管紧张素转换酶抑制剂 (ACEIs) 和血管紧张素受体阻滞剂 (ARBs)——的根本原因和影响仍不清楚。结合临床数据 ( n  = 144) 和气道样本的单细胞测序数据 ( n = 48) 通过体外实验，我们观察到高血压患者免疫细胞明显的炎症倾向，这与 COVID-19 的关键进展相关。ACEI 治疗与抑制 COVID-19 相关的过度炎症和增加细胞内在抗病毒反应有关，而 ARB 治疗与增强的上皮-免疫细胞相互作用有关。高血压患者的巨噬细胞和中性粒细胞，特别是在 ARB 治疗下，表现出更高的促炎细胞因子CCL3和CCL4以及趋化因子受体CCR1的表达. 尽管我们的队列规模有限，无法确定临床疗效，但我们的数据表明，ACEI 治疗对患有高血压的 COVID-19 患者的临床益处值得进一步研究。