COVID-19 as a viral functional ACE2 deficiency disorder with ACE2 related multi-organ disease

Gan, Rosemary; Rosoman, Nicholas; Henshaw, David J.E.; Noble, Euan P.; Georgius, Peter; Sommerfeld, Nigel

doi:10.1016/j.mehy.2020.110024

Cited by 49 publications

(61 citation statements)

References 40 publications

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“…The binding of SARS-CoV-2 to ACE2 causes the virus to enter cells and in turn reduces the bioavailability of ACE2. Due to the protective function of ACE2, the reduction of its levels is related to adverse clinical phenotypes, and its key role in the pathogenesis of SARS-Cov-2 has been described [ 17 ]. Evidence has shown that Ang II regulates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activation [ 18 , 19 , 20 , 21 ], when Ang II binds to angiotensin type 1 (AT1R) [ 22 ].…”

Section: Molecular Pathogenesis Of Covid-19mentioning

confidence: 99%

Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression

et al. 2020

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Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak emerged, countless efforts are being made worldwide to understand the molecular mechanisms underlying the coronavirus disease 2019 (COVID-19) in an attempt to identify the specific clinical characteristics of critically ill COVID-19 patients involved in its pathogenesis and provide therapeutic alternatives to minimize COVID-19 severity. Recently, COVID-19 has been closely related to sepsis, which suggests that most deceases in intensive care units (ICU) may be a direct consequence of SARS-CoV-2 infection-induced sepsis. Understanding oxidative stress and the molecular inflammation mechanisms contributing to COVID-19 progression to severe phenotypes such as sepsis is a current clinical need in the effort to improve therapies in SARS-CoV-2 infected patients. This article aims to review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress and inflammation, which can contribute to sepsis progression. We also provide an overview of potential antioxidant therapies and active clinical trials that might prevent disease progression or reduce its severity.

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Section: Molecular Pathogenesis Of Covid-19mentioning

confidence: 99%

Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression

et al. 2020

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“…These tests detect the presence of specific proteins called antibodies or immunoglobulins produced in response to antigen/s of the pathogen [ 7 ]. Moreover, antibody-based diagnostic tests at mass scale can help gather epidemiological data on infected cases, and track them for possible COVID-19 associated complications such as cardiovascular [ 8 , 9 , 10 , 11 ], neurological [ 12 , 13 , 14 , 15 ], and other unknown pathophysiological conditions [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Rapid Antibody-Based COVID-19 Mass Surveillance: Relevance, Challenges, and Prospects in a Pandemic and Post-Pandemic World

Augustine

Das

Hasan

et al. 2020

JCM

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The aggressive outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as COVID-19 (coronavirus disease-2019) pandemic demands rapid and simplified testing tools for its effective management. Increased mass testing and surveillance are crucial for controlling the disease spread, obtaining better pandemic statistics, and developing realistic epidemiological models. Despite the advantages of nucleic acid- and antigen-based tests such as accuracy, specificity, and non-invasive approaches of sample collection, they can only detect active infections. Antibodies (immunoglobulins) are produced by the host immune system within a few days after infection and persist in the blood for at least several weeks after infection resolution. Antibody-based tests have provided a substitute and effective method of ultra-rapid detection for multiple contagious disease outbreaks in the past, including viral diseases such as SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). Thus, although not highly suitable for early diagnosis, antibody-based methods can be utilized to detect past infections hidden in the population, including asymptomatic ones. In an active community spread scenario of a disease that can provide a bigger window for mass detections and a practical approach for continuous surveillance. These factors encouraged researchers to investigate means of improving antibody-based rapid tests and employ them as reliable, reproducible, sensitive, specific, and economic tools for COVID-19 mass testing and surveillance. The development and integration of such immunoglobulin-based tests can transform the pandemic diagnosis by moving the same out of the clinics and laboratories into community testing sites and homes. This review discusses the principle, technology, and strategies being used in antibody-based testing at present. It also underlines the immense prospect of immunoglobulin-based testing and the efficacy of repeated planned deployment in pandemic management and post-pandemic sustainable screenings globally.

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“…One of the most important hypotheses in the pathogenesis of COVID 19 is the COVID19 -RAS relationship. Gan et al, presented that the identification of angiotensin-converting-enzyme 2 (ACE2) as the receptor allowing viral entry to cells precipitated our interest in the role of ACE2 in COVID-19 pathogenesis [17]. They proposed that COVID-19 is a viral multisystem disease, with dominant vascular pathology, mediated by global reduction in ACE2 function, pronounced in disease conditions with RAS bias toward angiotensin-converting-enzyme (ACE) over ACE2.…”

Section: Introductionmentioning

confidence: 99%

“…It is further complicated by organ-specific pathology related to loss of ACE2 expressing cells particularly affecting the endothelium, alveolus, glomerulus, and cardiac microvasculature. The possible upregulation in ACE2 receptor expression may predispose individuals with aberrant RAS status to higher viral load on infection and relatively more cell loss [17].…”

Section: Introductionmentioning

confidence: 99%

New normal: two aspects of adipose tissue in COVID-19—treat and threat?

Çöpçü¹

2020

Expert Opinion on Biological Therapy

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Introduction: Adipose-derived stromal cells (ADSCs) can be an important alternative in COVID-19 prevention, treatment, and subsequent sequelae repair. However, ACE-2 plays a common role in the pathogenesis of adipocyte hypertrophy and COVID 19. Areas covered: In this 'Perspective,' the author would like to emphasize the use of adipose tissuederived stromal cells in COVID 19 and the issues that clinicians should pay attention to in fat graft applications in terms of adipose tissue-RAS relationship. The new normal for adipose tissue in COVID 19 will be highlighted. Expert Opinion: ADSCs may potentially be used in COVID-19. However, it has been speculated that ACE2 receptors are responsible for the pathogenesis of adipose tissue overgrowth and may be a potential danger in terms of the relationship between ACE2 receptors and COVID19. We speculate that reducing the size of overgrown fat tissue by ultra-sharp blades and using near-normal adipocytes will create a 'new normal.' ARTICLE HISTORY

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COVID-19 as a viral functional ACE2 deficiency disorder with ACE2 related multi-organ disease

Cited by 49 publications

References 40 publications

Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression

Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression

Rapid Antibody-Based COVID-19 Mass Surveillance: Relevance, Challenges, and Prospects in a Pandemic and Post-Pandemic World

New normal: two aspects of adipose tissue in COVID-19—treat and threat?

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