The Two-Way Switch Role of ACE2 in the Treatment of Novel Coronavirus Pneumonia and Underlying Comorbidities

Pang, Xiao Cong; Zhang, Han Xu; Zhang, Zhi; Suguro, Rinkiko; Chen, Yimin; Zhu, Yi‐Zhun

doi:10.3390/molecules26010142

Cited by 15 publications

(17 citation statements)

References 108 publications

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“…Staphylococcus aureus was mostly found in late VAPs ( p = 0.08) contrasting with the distribution of Gram-positive bacteria in VAP settings that are usually found in the early stages. Staphylococcus aureus has demonstrated the ability to interact and infect different cell strains, while becoming increasingly resistant to antibiotic therapy and a reservoir of bacteria that can make the infection difficult to treat [ 25 ]. However, this could simply be explained by a lack of power from low early VAP incidence.…”

Section: Discussionmentioning

confidence: 99%

Ventilator Acquired Pneumonia in COVID-19 ICU Patients: A Retrospective Cohort Study during Pandemia in France

Moreno¹,

Carvelli

Lesaux³

et al. 2023

JCM

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Describe the characteristics of ventilation-acquired pneumonia (VAP) and potential risk factors in critically ill Sars-Cov-2 patients admitted in three French public hospitals during the first year of the COVID-19 pandemic. We conducted a monocentric retrospective study in seven Marseille intensive care units (ICUs) aiming to describe VAP characteristics and identify their risk factors. VAP patients were compared to a non-VAP control group. From March to November 2020, 161 patients admitted for viral-induced acute respiratory failure (ARF) requiring invasive mechanical ventilation (IMV) were included. This cohort was categorized in two groups according to the development or not of a VAP during their stay in ICU. 82 patients (51%) developed ventilation-acquired pneumonia. Most of them were men (77%) and 55% had hypertension. In the VAP population, 31 out of 82 patients (38%) had received dexamethasone and 47% were administered antibiotic course prior to ICU admission. An amount of 88% of respiratory infections were late VAPs with a median delay of 10 days from the onset of IMV. Gram negative bacteria were responsible for 62% of VAPs with Pseudomonas spp. being the most documented bacteria. Less than a third of the ICU-acquired infections were due to multidrug resistant (MDR) bacteria mainly displaying AmpC cephalosporin hyper production resistance phenotype. Multivariate analysis revealed that early Dexamethasone administration in ICU, male sex, older age and ROX score were risk factors for VAP whereas pre-ICU antimicrobial treatment and higher IGS 2 were protective factors. VAP is a frequent ICU-related complication affecting half of patients infected with Sars-Cov-2 and requiring IMV. It was responsible for increased morbidity due to a longer ICU and hospital stay. VAP risk factors included demographic factors such as age and sex. Dexamethasone was associated with a threefold greater risk of developing VAP during ICU stay. These results need to be comforted by large multi-centric studies before questioning the only available and effective treatment against Sars-Cov-2 in ICU patients.

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Section: Discussionmentioning

confidence: 99%

Ventilator Acquired Pneumonia in COVID-19 ICU Patients: A Retrospective Cohort Study during Pandemia in France

Moreno¹,

Carvelli

Lesaux³

et al. 2023

JCM

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“…AT1R is localized at the epithelial brush border and is highly expressed in the circular and longitudinal muscle layers and the myenteric plexus [ 92 , 93 , 94 ]. Furthermore, because ACE2 is highly expressed on the luminal surface of the GI tract [ 10 , 95 ], SARS-CoV-2 has been reported to colonize the GI tract, particularly the intestines. SARS-CoV particles have been identified only in epithelial cells of the intestinal mucosa but not in the esophagus and stomach [ 96 , 97 ].…”

Section: Angiotensin II Type I Receptor (At1r) and Covid-19mentioning

confidence: 99%

“…Moreover, ACE2 downregulation in the intestine is related to the hyperactivation of the classical RAS axis [ 10 ]. ACE2 is normally involved in the control of dietary amino acid homeostasis, antimicrobial peptide expression, and gut microbial ecology [ 95 ].…”

Section: Angiotensin II Type I Receptor (At1r) and Covid-19mentioning

confidence: 99%

Angiotensin II Type I Receptor (AT1R): The Gate towards COVID-19-Associated Diseases

et al. 2022

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The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2), causes its downregulation, which subsequently leads to the dysregulation of the renin–angiotensin system (RAS) in favor of the ACE–angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis. AT1R has a major role in RAS by being involved in several physiological events including blood pressure control and electrolyte balance. Following SARS-CoV-2 infection, pathogenic episodes generated by the vasoconstriction, proinflammatory, profibrotic, and prooxidative consequences of the Ang II–AT1R axis activation are accompanied by a hyperinflammatory state (cytokine storm) and an acute respiratory distress syndrome (ARDS). AT1R, a member of the G protein-coupled receptor (GPCR) family, modulates Ang II deleterious effects through the activation of multiple downstream signaling pathways, among which are MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases (PDGF, EGFR, insulin receptor), and nonreceptor tyrosine kinases (Src, JAK/STAT, focal adhesion kinase (FAK)), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. COVID-19 is well known for generating respiratory symptoms, but because ACE2 is expressed in various body tissues, several extrapulmonary pathologies are also manifested, including neurologic disorders, vasculature and myocardial complications, kidney injury, gastrointestinal symptoms, hepatic injury, hyperglycemia, and dermatologic complications. Therefore, the development of drugs based on RAS blockers, such as angiotensin II receptor blockers (ARBs), that inhibit the damaging axis of the RAS cascade may become one of the most promising approaches for the treatment of COVID-19 in the near future. We herein review the general features of AT1R, with a special focus on the receptor-mediated activation of the different downstream signaling pathways leading to specific cellular responses. In addition, we provide the latest insights into the roles of AT1R in COVID-19 outcomes in different systems of the human body, as well as the role of ARBs as tentative pharmacological agents to treat COVID-19.

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“…The S protein of SARS-CoV-2 contains a receptor-binding domain (RBD) that specifically recognizes the angiotensin-converting enzyme-2 (ACE2) receptors. RBD is a critical target for antiviral compounds and antibodies; however, nucleocapsid protein (N) and other structural or non-structural SARS-CoV-2 proteins can elicit the host immune response as well [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Immunity after COVID-19 Recovery and Vaccination: Similarities and Differences

et al. 2022

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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with a robust immune response. The development of systemic inflammation leads to a hyperinflammatory state due to cytokine release syndrome during severe COVID-19. The emergence of many new SARS-CoV-2 variants across the world deteriorates the protective antiviral immunity induced after infection or vaccination. The innate immune response to SARS-CoV-2 is crucial for determining the fate of COVID-19 symptomatology. T cell-mediated immunity is the main factor of the antiviral immune response; moreover, SARS-CoV-2 infection initiates a rapid B-cell response. In this paper, we present the current state of knowledge on immunity after COVID-19 infection and vaccination. We discuss the mechanisms of immune response to various types of vaccines (nucleoside-modified, adenovirus-vectored, inactivated virus vaccines and recombinant protein adjuvanted formulations). This includes specific aspects of vaccination in selected patient populations with altered immune activity (the elderly, children, pregnant women, solid organ transplant recipients, patients with systemic rheumatic diseases or malignancies). We also present diagnostic and research tools available to study the anti-SARS-CoV-2 cellular and humoral immune responses.

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The Two-Way Switch Role of ACE2 in the Treatment of Novel Coronavirus Pneumonia and Underlying Comorbidities

Cited by 15 publications

References 108 publications

Ventilator Acquired Pneumonia in COVID-19 ICU Patients: A Retrospective Cohort Study during Pandemia in France

Ventilator Acquired Pneumonia in COVID-19 ICU Patients: A Retrospective Cohort Study during Pandemia in France

Angiotensin II Type I Receptor (AT1R): The Gate towards COVID-19-Associated Diseases

Immunity after COVID-19 Recovery and Vaccination: Similarities and Differences

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