血管紧张素转换酶(ACE)抑制剂可缓解COVID-19高炎症反应:一项深度免疫表型观察研究

Venkata R Duvvuri, Andrew Baumgartner, Sevda Molani, Patricia V Hernandez, Dan Yuan, Ryan T Roper, Wanessa F Matos, Max Robinson, Yapeng Su, Naeha Subramanian, Jason D Goldman, James R Heath, Jennifer J Hadlock
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引用次数: 4

摘要

背景:血管紧张素转换酶抑制剂(ACEi)和血管紧张素- ii受体阻滞剂(ARB)是最常用的抗高血压药物,通过诱导血管紧张素转换酶2 (ACE2)的表达来对抗肾素-血管紧张素-醛固酮系统(RAAS)的激活。考虑到ACE2是SARS-CoV-2进入宿主细胞的功能受体,ACEi和ARB与COVID-19结局的关系需要深入评估。方法:采用电子健康记录(EHRs)中未匹配和倾向评分(PS)匹配的队列进行回顾性分析,评估RAAS抑制剂对住院COVID-19患者接受有创机械通气(IMV)风险和30天死亡率的影响。此外,我们通过观察性前瞻性队列研究了先前使用抗高血压治疗的住院COVID-19患者的免疫细胞基因表达谱。结果:回顾性分析显示,使用ACEi或ARB均未增加风险。事实上,使用ACEi可以降低死亡风险。使用ps匹配队列的生存分析表明,与非RAAS药物和未服用抗高血压药物的患者相比,RAAS抑制剂与住院时间和住院死亡率之间没有显著关系。通过对基因表达谱的分析,我们观察到在先前使用ACE抑制剂的患者中,单核细胞中1L1R2(一种抗炎受体)和RETN(一种免疫抑制标志物)基因的表达明显上调。结论:总体而言,研究结果不支持停用ACEi或ARB治疗,并提示ACEi可能会减轻COVID-19的高炎症反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Angiotensin-Converting Enzyme (ACE) Inhibitors May Moderate COVID-19 Hyperinflammatory Response: An Observational Study with Deep Immunophenotyping.

Angiotensin-Converting Enzyme (ACE) Inhibitors May Moderate COVID-19 Hyperinflammatory Response: An Observational Study with Deep Immunophenotyping.

Angiotensin-Converting Enzyme (ACE) Inhibitors May Moderate COVID-19 Hyperinflammatory Response: An Observational Study with Deep Immunophenotyping.

Angiotensin-Converting Enzyme (ACE) Inhibitors May Moderate COVID-19 Hyperinflammatory Response: An Observational Study with Deep Immunophenotyping.

Background: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARB), the most commonly prescribed antihypertensive medications, counter renin-angiotensin-aldosterone system (RAAS) activation via induction of angiotensin-converting enzyme 2 (ACE2) expression. Considering that ACE2 is the functional receptor for SARS-CoV-2 entry into host cells, the association of ACEi and ARB with COVID-19 outcomes needs thorough evaluation.

Methods: We conducted retrospective analyses using both unmatched and propensity score (PS)-matched cohorts on electronic health records (EHRs) to assess the impact of RAAS inhibitors on the risk of receiving invasive mechanical ventilation (IMV) and 30-day mortality among hospitalized COVID-19 patients. Additionally, we investigated the immune cell gene expression profiles of hospitalized COVID-19 patients with prior use of antihypertensive treatments from an observational prospective cohort.

Results: The retrospective analysis revealed that there was no increased risk associated with either ACEi or ARB use. In fact, the use of ACEi showed decreased risk for mortality. Survival analyses using PS-matched cohorts suggested no significant relationship between RAAS inhibitors with a hospital stay and in-hospital mortality compared to non-RAAS medications and patients not on antihypertensive medications. From the analysis of gene expression profiles, we observed a noticeable up-regulation in the expression of 1L1R2 (an anti-inflammatory receptor) and RETN (an immunosuppressive marker) genes in monocytes among prior users of ACE inhibitors.

Conclusion: Overall, the findings do not support the discontinuation of ACEi or ARB treatment and suggest that ACEi may moderate the COVID-19 hyperinflammatory response.

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