Impact of the Angiotensin-Converting Enzyme (ACE) Inhibitors on the Course of the Acute Respiratory Distress Syndrome (ARDS) Developed During COVID-19 and Other Severe Respiratory Infections Under Hyperferritinemia Conditions: A Cohort Study.

Abstract

Background: Angiotensin-converting enzyme 2 (ACE2) is not only the entry route of SARS-CoV-2 infection but also triggers a major mechanism of COVID-19 aggravation by promoting a hyperinflammatory state, leading to lung injury, hematological and immunological dysregulation. The impact of ACE2 inhibitors on the course of COVID-19 is still unclear. The effect of ACE2 inhibitors on the course of acute respiratory distress syndrome (ARDS) during COVID-19 and other severe respiratory infections in conditions of hyperferritinemia (HF) was investigated.

Methods: A cohort study of critically ill patients with COVID-19 and other respiratory diseases (widespread infection, pneumonia) who underwent treatment in The Critical Care Unit of the First University Clinic (Tbilisi, Georgia) during the 2020-2021 years was conducted. The impact of the ACE2 inhibitors on the course of the ARDS developed during COVID-19 and other severe respiratory infections in conditions of different severity of HF was evaluated.

Results: In COVID-19-infected (I) and uninfected (II) patients with ARDS, ACE2 inhibitors reduce the levels of Ang II, C reactive protein (CRP) and D-dimer (I: from 1508.07  ±  26.68 to 48.51  ±  24.35, from 233.92  ±  13.02 to 198.12  ±  11.88, from 7.88  ±  0.47 to 6.28  ±  0.43; II: from 1000.14  ±  149.49 to 46.23  ±  88.21, 226.48  ±  13.81 to 183.52  ±  17.32, from 6.39  ±  0.58 to 5.48  ±  0.69) at moderate HF and Ang II, CRP levels (I: from 1845.89  ±  89.37 to 49.64  ±  51.05, from 209.28  ±  14.41 to 175.37  ±  9.84; II: from 1753.29  ±  65.95 to 49.76  ±  55.74, 287.10  ±  20.50 to 214.71  ±  17.32) at severe HF, reduce interleukin-6 (IL-6) expression at moderate HF (I: from 1977.23  ±  354.66 to 899.36  ±  323.76) and cause reduction of pCO₂ index at severe HF (I: from 69.80  ±  3.22 to 60.44  ±  2.20) in COVID-19-infected patients.

Conclusion: Study results show that the ACE2 inhibitors play an important role in the regulation of inflammatory processes in both COVID-19-infected and uninfected patients with ARDS. ACE2 inhibitors decrease immunological disorders, inflammation, and lung alveoli dysfunction, especially in COVID-19-infected patients.