march 2020 • New England Journal of Medicine

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

Muthiah Vaduganathan, Orly Vardeny, Thomas Michel, John J.V. McMurray, et al.

DOI: 10.1056/NEJMsr2005760

Key message

Os autores sugerem os seguintes pontos-chave da relação entre Covid19 e o Sistema Renina-Angiotensina-Aldosterona:- ACE2, uma enzima que contraria fisiologicamente a ativação do RAAS, é o receptor funcional do SARS-CoV-2, o vírus responsável pela pandemia de Covid-19- Estudos pré-clínicos selecionados sugeriram que os inibidores do RAAS podem aumentar a expressão da ACE2, levantando preocupações sobre a segurança em pacientes com Covid-19- Dados insuficientes estão disponíveis para determinar se essas observações se traduzem prontamente em seres humanos e nenhum estudo avaliou os efeitos dos inibidores do RAAS no Covid-19- Ensaios clínicos estão em andamento para testar a segurança e eficácia dos moduladores de RAAS, incluindo a combinação ACE2 humano e losartan ARB em Covid-19- A retirada abrupta de inibidores do RAAS em pacientes de alto risco, incluindo aqueles com insuficiência cardíaca ou enfarte do miocárdio, pode resultar em instabilidade clínica e resultados adversos à saúde- Até que dados adicionais estejam disponíveis, acreditamos que os inibidores do RAAS devem ser continuados em pacientes em condições estáveis que correm risco, sendo suspeitos ou confirmados com Covid-19


The renin–angiotensin–aldosterone system (RAAS) is an elegant cascade of vasoactive peptides that orchestrate key processes in human physiology. Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and SARS-CoV-2, which have been responsible for the SARS epidemic in 2002 to 2004 and for the more recent coronavirus disease 2019 (Covid-19) pandemic, respectively, interface with the RAAS through angiotensin-converting enzyme 2 (ACE2), an enzyme that physiologically counters RAAS activation but also functions as a receptor for both SARS viruses.The interaction between the SARS viruses and ACE2 has been proposed as a potential factor in their infectivity, and there are concerns about the use of RAAS inhibitors that may alter ACE2 and whether variation in ACE2 expression may be in part responsible for disease virulence in the ongoing Covid-19 pandemic. Indeed, some media sources and health systems have recently called for the discontinuation of ACE inhibitors and angiotensin-receptor blockers (ARBs), both prophylactically and in the context of suspected Covid-19.Given the common use of ACE inhibitors and ARBs worldwide, guidance on the use of these drugs in patients with Covid-19 is urgently needed. Here, we highlight that the data in humans are too limited to support or refute these hypotheses and concerns. Specifically, we discuss the uncertain effects of RAAS blockers on ACE2 levels and activity in humans, and we propose an alternative hypothesis that ACE2 may be beneficial rather than harmful in patients with lung injury. We also explicitly raise the concern that withdrawal of RAAS inhibitors may be harmful in certain high-risk patients with known or suspected Covid-19.