Increased Angiotensin-Converting Enzyme 2 and Loss of Alveolar Type II Cells in COVID-19–related Acute Respiratory Distress Syndrome

Gérard, Ludovic; Lecocq, Marylène; Bouzin, Caroline; Hoton, Delphine; Schmit, G.; Pereira, João Pinto; Montiel, Virginie; Planté-Bordeneuve, Thomas; Laterre, Pierre‐François; Pilette, Charles

doi:10.1164/rccm.202012-4461oc

Cited by 60 publications

(66 citation statements)

References 52 publications

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“…The authors suggested that hrsACE2 could block the systemic spread of the virus from the lung to other organs [ 30 ]. One previous study has demonstrated a significant increase in lung endothelial cell immunostaining for ACE2 and for serum ACE2 levels in 15 COVID-19 patients with ARDS and 13 non-COVID-19 patients with ARDS compared to control tissues from patients who had a lobectomy for lung cancer [ 31 ]. This suggests that differences in sACE2 may reflect the presence of COVID-19-induced ARDS, which reversed over time/with treatment.…”

Section: Discussionmentioning

confidence: 99%

Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery

Mortaz

Jamaati

Roofchayee

et al. 2022

Heliyon

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Section: Discussionmentioning

confidence: 99%

Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery

Mortaz

Jamaati

Roofchayee

et al. 2022

Heliyon

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“…A logical explanation would be the previous observation that COVID-19 patients display reduced ACE levels [ 9 – 11 ]. This is due to the fact that severe lung injury (as occurring in severe COVID-19 patients) induces endothelial dysfunction and loss of pulmonary ACE expression [ 11 , 12 ]. Here, it is important to note that the majority of ACE is expressed on the surface of endothelial cells [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Severe COVID-19 patients display elevated soluble ACE2 levels [ 4 – 8 ], demonstrating that virus infectivity is accompanied by ACE2 shedding. At the same time, serum ACE levels are decreased in COVID-19 patients [ 9 – 11 ], with the greatest drop occurring in the most severe cases. This parallels the observation that lung injury, as occurring in acute respiratory distress syndrome (ARDS), results in diminished pulmonary ACE activity [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

A low aldosterone/renin ratio and high soluble ACE2 associate with COVID-19 severity

Akın

Schriek²,

Nieuwkoop

et al. 2021

Journal of Hypertension

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Background: The severity of COVID-19 after SARS-CoV-2 infection is unpredictable. Angiotensin-converting enzyme-2 (ACE2) is the receptor responsible for coronavirus binding, while subsequent cell entry relies on priming by the serine protease TMPRSS2 (transmembrane protease, serine 2). Although renin-angiotensin-aldosterone-system (RAAS) blockers have been suggested to upregulate ACE2, their use in COVID-19 patients is now considered well tolerated. The aim of our study was to investigate parameters that determine COVID-19 severity, focusing on RAAS-components and variation in the genes encoding for ACE2 and TMPRSS2. Methods: Adult patients hospitalized due to SARS-CoV-2 infection between May 2020 and October 2020 in the Haga Teaching Hospital were included, and soluble ACE2 (sACE2), renin, aldosterone (in heparin plasma) and polymorphisms in the ACE2 and TMPRSS2 genes (in DNA obtained from EDTA blood) were determined. Measurements and main results: Out of the 188 patients who were included, 60 were defined as severe COVID-19 (ICU and/or death). These patients more often used antidiabetic drugs, were older, had higher renin and sACE2 levels, lower aldosterone levels and a lower aldosterone/renin ratio. In addition, they displayed the TMPRSS2-rs2070788 AA genotype less frequently. No ACE2 polymorphism-related differences were observed. Multivariate regression analysis revealed independent significance for age, sACE2, the aldosterone/renin ratio, and the TMPRSS2 rs2070788 non-AA genotype as predictors of COVID-19 severity, together yielding a C-index of 0.79. Findings were independent of the use of RAAS blockers. Conclusion: High sACE2, a low aldosterone/renin ratio and having the TMPRSS2 rs2070788 non-AA genotype are novel independent determinants that may help to predict COVID-19 disease severity. Trial registration: retrospectively registered.

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“…In addition, an elevated level of Ang-II was found in patients with H5N1 or H7N9 infection, and these elevated levels were related to the severity of the pulmonary injury [52]. Gerard et al [53] investigated the expression and distribution of ACE2 in COVID-19 and showed that the expression of ACE2 increased in lung tissues, serum, and endothelial cells but decreased in alveolar epithelial cells (AT2). Asaka et al [54] explored the pathogenicity of COVID-19 and found that CAG-hACE2 mice were susceptible to SARS-CoV-2 and the levels of cytokines and chemokines increased, resulting in acute lung injury, while injecting the plasma of immunized mice could reduce the mortality of mice.…”

Section: Ace2 and Sars-cov-2 In Alimentioning

confidence: 99%

ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review

Chen

Yin

et al. 2021

IJMS

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Despite the protracted battle against coronavirus acute respiratory infection (COVID-19) and the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), no specific and effective drugs have to date been reported. Angiotensin-converting enzyme 2 (ACE2) is a zinc metalloproteinase and a critical modulator of the renin-angiotensin system (RAS). In addition, ACE2 has anti-inflammatory and antifibrosis functions. ACE has become widely known in the past decade as it has been identified as the primary receptor for SARS-CoV and SARS-CoV-2, being closely associated with their infection. SARS-CoV-2 primarily targets the lung, which induces a cytokine storm by infecting alveolar cells, resulting in tissue damage and eventually severe acute respiratory syndrome. In the lung, innate immunity acts as a critical line of defense against pathogens, including SARS-CoV-2. This review aims to summarize the regulation of ACE2, and lung host cells resist SARS-CoV-2 invasion by activating innate immunity response. Finally, we discuss ACE2 as a therapeutic target, providing reference and enlightenment for the clinical treatment of COVID-19.

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Increased Angiotensin-Converting Enzyme 2 and Loss of Alveolar Type II Cells in COVID-19–related Acute Respiratory Distress Syndrome

Cited by 60 publications

References 52 publications

Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery

Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery

A low aldosterone/renin ratio and high soluble ACE2 associate with COVID-19 severity

ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review

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