ACE inhibitors also work in COVID-19

At the beginning of the corona pandemic, antihypertensive drugs from the group of ACE inhibitors and angiotensin receptor blockers (ARBs) were suspected to increase the risk of infection and to influence the course of COVID-19 negatively. The assumption relied on preclinical observations that these substances increase the presence of the SARS-CoV-2 viral receptor ACE2 on the cell membrane - the regulation is known for a long time.

Over time, several extensive observational studies (published in the New England Journal of Medicine) disproved this assumption. Researchers concluded that therapy with ACE inhibitors or ARBs has no adverse effects on COVID-19 patients and does not increase the risk of infection. To date, however, the pharmacological effects of both substances have not been directly investigated in COVID-19 patients.
 
ACE inhibitors and ARBs influence the plasma levels of so-called angiotensin peptides through their mode of action. The regulation of these peptides and their binding to target receptors then mediates the therapeutic effect, such as blood pressure reduction. The study by Ulrich Kintscher of Charité – Universitätsmedizin Berlin, a partner institution of the DZHK, is now the first study to directly investigate the pharmacological effect of drugs on the regulation of these angiotensin peptides, using measurements from plasma samples of COVID-19 patients treated with ACE inhibitors or ARBs, and control samples.
 
These analyses were carried out using chromatographic and mass spectrometric methods on a total of 58 patients, 31 of whom were suffering from COVID-19. The results showed that no significant differences between untreated controls and COVID-19 patients could be detected in any of the parameters examined. Also, it was demonstrated that ACE inhibitors mediate a comparable pharmacological-therapeutic effect, especially concerning ACE inhibition, in controls and COVID-19 patients. In COVID-19 patients treated with ACE inhibitors, plasma ACE2 activity was increased compared to the other groups.
 
So, in summary, the study shows (1) COVID-19 patients do not show abnormal regulation of the renin-angiotensin system (at the level of angiotensin peptides), (2) the use of antihypertensive drugs from the class of ACE inhibitors and ARBs leads to comparable pharmacological effects concerning their therapeutic impact in SARS-CoV-2 negative and COVID-19 patients, determined by plasma angiotensin peptide levels, and (3) ACE inhibitors lead to an increase in plasma ACE2 in COVID-19, although the significance of this regulation, in contrast to the regulation of membrane ACE2, is still unclear.

Original work: Plasma Angiotensin Peptide Profiling and ACE2-Activity in COVID-19 Patients treated with Pharmacological Blockers of the Renin Angiotensin System, Kintscher et. al. Hypertension, 27 Aug 2020 https://doi.org/10.1161/HYPERTENSIONAHA.120.15841