Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19

Abstract

S pe c i a l R e p o r tT h e ne w e ngl a nd jou r na l o f m e dicine n engl j med nejm.org T h e ne w e ngl a nd jou r na l o f m e dicine n engl j med nejm.org

Renin-angiotensin-aldosterone system and COVID-19 infection

“…Angiotensin-converting enzyme 2 (ACE2) is an enzyme (carboxypeptidase) mainly located in the membrane, circulating forms being created by enzyme splicing of the membrane anchor; it is homologous to the angiotensin-converting enzyme (formerly simply known as ACE but now better denoted ACE1) first described in 2000 (3,4). ACE2 downregulates the renin-angiotensin system and acts as a deactivator of angiotensin II (also known as angiotensin-(1-8), an active peptide causing vasoconstriction, pro-fibrosis, pro-inflammation action, stimulating aldosterone secretion by binding to the AT1 receptor), converting it into angiotensin-(1-7), an active peptide with opposite properties to angiotensin II (5). Several animal studies showed that angiotensin-(1-7), by binding to the Mas receptor, induced vasodilatation and showed anti-fibrosis and anti-inflammatory properties (6) ( Figure 1).…”

“…Therefore, it is clear that ACE2 and particularly its membrane expression and tissue activity play a key role in COVID-19 infection. The exact roles, however, are complex and may be deleterious in the contamination phase, as ACE2 acts as a receptor to COVID-19 (and severity may correlate with membrane expression and tissue activity) (28,29) while being beneficial in the inflammatory lesion phase (5,30). Many questions thus remain at present unanswered.…”

“…Some studies reported high levels of ACEi/ARB in COVID-19 infection, and especially in severe forms requiring hospital or ICU admission, although it should be noticed that arterial hypertension is very common, especially in the elderly, for which ACEi/ARB is prescribed in 25-30% of cases (5). Thus the positive or negative impact of ACEi/ARB in COVID-19 in humans remains unknown and is complex (44), possibly even depending on clinical stage: negative in the contamination phase but beneficial in the tissue inflammation phase (45,46).…”

“…European Society of Cardiology (see http://www.sfhta.eu/?p=6670), and many publications (5,49,50) advise against stopping maintenance treatments in an attempt to "prevent" COVID-19 infection, It should also be noticed that the effects of ACEi and of ARB in COVID-19 infection are unknown, and that the two may not be the same. Guidelines may be rapidly revised in the light of incoming data from ongoing clinical trials, especially concerning ARB.…”

Bloqueantes del sistema renina-angiotensina e infección por COVID-19

“…De forma paralela, se han publicado recientemente nuevos datos que revisan de forma más extensa y estructurada la justificación de la ausencia de necesidad de suspender los inhibidores del SRA (4,5,6). Además, en un meta-análisis reciente, los inhibidores del SRA demostraron ser beneficiosos en pacientes con lesiones pulmonares agudas o distrés respiratorio (7).…”