ACE2 (Angiotensin-Converting Enzyme 2), COVID-19, and ACE Inhibitor and Ang II (Angiotensin II) Receptor Blocker Use During the Pandemic

South, Andrew M.; Brady, Tammy M.; Flynn, Joseph T.

doi:10.1161/hypertensionaha.120.15291

Cited by 120 publications

(119 citation statements)

References 67 publications

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“…Increased susceptibility to other respiratory viral diseases in childhood can, by a competitive mechanism, limit infection with SARS-CoV-2. In addition, cross-reactive antibodies for these other infections, including other coronaviruses, might play a partly protective role against SARS-CoV-2 [17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

Clinical laboratory and dispersion pattern of COVID-19 in a family cluster in the social-distancing period

Brito

Brito²,

Martins³

et al. 2020

J Infect Dev Ctries

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Introduction: Since the first reports of coronavirus disease 2019 (COVID-19) in December 2019, the disease has spread worldwide. Different social isolation strategies have been adopted to reduce community transmission, but few studies have evaluated the pattern of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection in a family cluster during periods of isolation. We report an outbreak in 24 members of a family cluster during a period of social distancing. Methodology: We carried out an observational descriptive study of a family cluster infected with SARS-CoV-2 in Pernambuco, Northeast Brazil. Laboratory confirmation included RT-PCR of nasopharyngeal samples or IgM or IgG serology. Results: The attack rates were 75% (19/24) based on laboratory-confirmed cases and 87.5% (21/24) including probable cases. The time of spread was 17 days from the first case. All patients had mild symptoms, requiring no hospitalization, and none of them died. The frequency of symptomatic, laboratory-confirmed patients was higher among adults (94%) than among children (50%); the paediatric age group also had a higher frequency of exposed individuals who remained negative for infection. Ground-glass opacities on chest computed tomography were present in all patients with reported dyspnoea. Conclusion: This study highlights a high risk of intrahousehold transmission from an index case, suggesting the need for (I) specific guidelines during periods of social distancing, (II) minimization of external exposures and, above all, (III) adoption of strict quarantine measures for suspected cases and family members to prevent outbreaks from spreading.

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Section: Discussionmentioning

confidence: 99%

Clinical laboratory and dispersion pattern of COVID-19 in a family cluster in the social-distancing period

Brito

Brito²,

Martins³

et al. 2020

J Infect Dev Ctries

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“…Hence, following the SARS-CoV-2 outbreak, it has been speculated that the use of ACEI and ARB could increase viral invasion and should therefore be temporarily suspended. This topic has been abundantly debated in the last few months (March-May 2020), with contradictory views (Bavishi et al, 2020;Buckley et al, 2020;Danser et al, 2020;Fang et al, 2020;Huang Z. et al, 2020;Kreutz et al, 2020;Kuster et al, 2020;Mourad and Levy, 2020;Park et al, 2020;Rico-Mesa et al, 2020;Sommerstein et al, 2020;South et al, 2020;Tignanelli et al, 2020;Vaduganathan et al, 2020;Verdecchia et al, 2020b;Zhang P. et al, 2020). As a consequence of this debate, several clinical societies have stated that suspension of ACEI and ARB is not justified on the basis of the present scientific evidence, although a recent BMJ editorial (Aronson and Ferner, 2020) suggested to consider stopping ACE inhibitors or angiotensin receptor blockers in patients with mild hypertension who are at high risk of coronavirus infection.…”

Section: The Controversial Role Of Ace2 Expressionmentioning

confidence: 99%

ACE2 in the Era of SARS-CoV-2: Controversies and Novel Perspectives

Saponaro

Rutigliano

Sestito

et al. 2020

Front. Mol. Biosci.

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Angiotensin-converting enzyme 2 (ACE2) is related to ACE but turned out to counteract several pathophysiological actions of ACE. ACE2 exerts antihypertensive and cardioprotective effects and reduces lung inflammation. ACE2 is subjected to extensive transcriptional and post-transcriptional modulation by epigenetic mechanisms and microRNAs. Also, ACE2 expression is regulated post-translationally by glycosylation, phosphorylation, and shedding from the plasma membrane. ACE2 protein is ubiquitous across mammalian tissues, prominently in the cardiovascular system, kidney, and intestine. ACE2 expression in the respiratory tract is of particular interest, in light of the discovery that ACE2 serves as the initial cellular target of severe acute respiratory syndrome (SARS)-coronaviruses, including the recent SARS-CoV2, responsible of the COronaVIrus Disease 2019 (COVID-19). Since the onset of the COVID-19 pandemic, an intense effort has been made to elucidate the biochemical determinants of SARS-CoV2-ACE2 interaction. It has been determined that SARS-CoV2 engages with ACE2 through its spike (S) protein, which consists of two subunits: S1, that mediates binding to the host receptor; S2, that induces fusion of the viral envelope with the host cell membrane and delivery of the viral genome. Owing to the role of ACE2 in SARS-CoV2 pathogenicity, it has been speculated that medical conditions, i.e., hypertension, and/or drugs, i.e., ACE inhibitors and angiotensin receptor blockers, known to influence ACE2 density could alter the fate of SARS-CoV-2 infection. The debate is still open and will only be solved when results of properly designed experimental and clinical investigations will be made public. An interesting observation is, however that, upon infection, ACE2 activity is reduced either by downregulation or by shedding. These events might precipitate the so-called "cytokine storm" that characterizes the most severe COVID-19 forms. As evidence accumulates, ACE2 appears a druggable target in the attempt to limit virus entry and replication. Strategies aimed at blocking ACE2 with antibodies, small molecules or peptides, or at neutralizing the virus by competitive binding with exogenously administered ACE2, are currently under investigations. In this review, we will present an overview of the state-of-the-art knowledge on ACE2 biochemistry and pathophysiology, outlining open issues in the context of COVID-19 disease and potential experimental and clinical developments.

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“…On the other hand, discontinuation of RAS inhibitors might further intensify the uncontrolled action of Ang II, shown in Figure 1B , leaving it unopposed once Ang 1-7 generation is hampered. Those in favor of uninterrupted administration of RAS inhibitors would argue that, as illustrated in Figure 1C , depleting Ang II or blocking its action on AT1R [by ACE inhibitors or Ang-receptor blockers (ARBs), respectively] would balance the exhaustion of Ang 1-7 caused by viral invasion and might prevent consequent vasoconstriction ( South et al, 2020 ). Furthermore, it is also likely that the profile of Ang derivatives may differ in patients treated by ARBs, by ACE inhibitors or by spironolactone ( Malha et al, 2020 ).…”

Section: Knowledge Gaps: the Missing Pieces In The Puzzlementioning

confidence: 99%

“…Most of the clinical trials and data analysis are performed on adults, however potential differences between adults and children may exist, thus coronavirus-related research should be undertaken in children as well, including the impact of ACE-I and ARBs on COVID-19 evolvement among this subpopulation. Hopefully, this may provide clues for the question why children are at decreased risk of severe COVID-19 disease ( South et al, 2020 ). Furthermore, we have no idea about the function or malfunction of circulating sACE2 following its shedding from cell membranes.…”

Section: Knowledge Gaps: the Missing Pieces In The Puzzlementioning

confidence: 99%

ACE2, COVID-19 Infection, Inflammation, and Coagulopathy: Missing Pieces in the Puzzle

et al. 2020

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Engulfed by the grave consequences of the coronavirus disease 2019 (COVID-19) pandemic, a better understanding of the unique pattern of viral invasion and virulence is of utmost importance. Angiotensin (Ang)-converting enzyme (ACE) 2 is a key component in COVID-19 infection. Expressed on cell membranes in target pulmonary and intestinal host cells, ACE2 serves as an anchor for initial viral homing, binding to COVID-19 spike-protein domains to enable viral entry into cells and subsequent replication. Viral attachment is facilitated by a multiplicity of membranal and circulating proteases that further uncover attachment loci. Inherent or acquired enhancement of membrane ACE2 expression, likely leads to a higher degree of infection and may explain the predisposition to severe disease among males, diabetics, or patients with respiratory or cardiac diseases. Additionally, once attached, viral intracellular translocation and replication leads to depletion of membranal ACE2 through degradation and shedding. ACE2 generates Ang 1-7, which serves a critical role in counterbalancing the vasoconstrictive, pro-inflammatory, and pro-coagulant effects of ACE-induced Ang II. Therefore, Ang 1-7 may decline in tissues infected by COVID-19, leading to unopposed deleterious outcomes of Ang II. This likely leads to microcirculatory derangement with endothelial damage, profound inflammation, and coagulopathy that characterize the more severe clinical manifestations of COVID-19 infection. Our understanding of COVID-ACE2 associations is incomplete, and some conceptual formulations are currently speculative, leading to controversies over issues such as the usage of ACE inhibitors or Ang-receptor blockers (ARBs). This highlights the importance of focusing on ACE2 physiology in the evaluation and management of COVID-19 disease.

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ACE2 (Angiotensin-Converting Enzyme 2), COVID-19, and ACE Inhibitor and Ang II (Angiotensin II) Receptor Blocker Use During the Pandemic

Cited by 120 publications

References 67 publications

Clinical laboratory and dispersion pattern of COVID-19 in a family cluster in the social-distancing period

Clinical laboratory and dispersion pattern of COVID-19 in a family cluster in the social-distancing period

ACE2 in the Era of SARS-CoV-2: Controversies and Novel Perspectives

ACE2, COVID-19 Infection, Inflammation, and Coagulopathy: Missing Pieces in the Puzzle

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