Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19

Li, Guoping; He, Xiang; Zhang, Lei; Qin, Ran; Wang, Junyi; Xiong, Anying; Wu, Dehong; Chen, Feng; Sun, Jin‐Lyu; Chang, Christopher

doi:10.1016/j.jaut.2020.102463

Cited by 255 publications

(277 citation statements)

References 30 publications

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“…Previous studies have evaluated ACE2 expression in the respiratory tract. Studies of ACE2 mRNA transcript abundance have provided conflicting interpretations, as well as a lack of protein validation (12)(13)(14)(15)(16)(17)(18)(19). ACE2 protein studies have been limited by a paucity of lung tissue substrates and reports that have yielded contradictory results (20-23) (Supplemental Table 1).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract

Bezara

Thurman

Pezzulo

et al. 2020

Preprint

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15Running title: Expression of ACE2 in the human respiratory tract 16 17 Impact: The mapping of ACE2, the receptor for SARS-CoV-2, to specific anatomical regions 18 and to particular cell types in the human respiratory tract will help guide future studies and 19 provide molecular targets for antiviral therapies. We saw no increase of receptor expression in 20 the presence of known risk factors for severe coronavirus disease 2019. 21 22 Abstract: 35 Rationale: Zoonotically transmitted coronaviruses are responsible for three disease 36 outbreaks since 2002, including the current coronavirus disease 2019 pandemic, caused by 37 SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding 38 the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the cellular 39 receptor for SARS-CoV-2. Receptor expression on the cell surface facilitates viral binding and 40 entry. However, reports of the abundance and distribution of ACE2 expression in the respiratory 41 tract are limited and conflicting. Objectives: To determine ACE2 expression in the human 42 respiratory tract and its association with demographic and clinical characteristics. Methods: 43Here, we systematically examined human upper and lower respiratory tract cells using single-cell 44 RNA sequencing and immunohistochemistry to determine where the receptor is expressed. 45Measurements and main results: Our results reveal that ACE2 expression is highest within the 46 sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe 47 disease development, respectively. In the lung parenchyma where severe disease occurs, ACE2 48 was found on the apical surface of a small subset of alveolar type II cells. We saw no increase of 49 receptor expression in the presence of known risk factors for severe coronavirus disease 2019. 50Conclusions: The mapping of ACE2 to specific anatomical regions and to particular cell types in 51 the respiratory tract will help guide future studies and provide molecular targets for antiviral 52 therapies. 53 54 Word count: 223 55

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Section: Introductionmentioning

confidence: 99%

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract

Bezara

Thurman

Pezzulo

et al. 2020

Preprint

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“…Additionally, these patients are at higher risk for infection also because of COVID-19 use angiotensin converting enzyme 2 (ACE2) receptors to enter the host cell (36). The ACE2 is expressed in different tissues: kidney, lung, heart and adipose tissue (36). infection leads to an upregulation of the genes associated with lipid metabolism, involved in the regulation of inflammation (37).…”

Section: Discussionmentioning

confidence: 99%

Fat mass prevalence and influence on nutritional status in ICU COVID-19 patients

Lorenzo

Tarsitano

Falcone

et al. 2020

Preprint

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Background: Obesity and steatosis are associated with COVID-19 severe pneumonia. Elevated levels of pro-inflammatory cytokines and reduced immune response are typical of these patients. In particular, adipose tissue is the organ playing the crucial role. So, it is necessary to evaluate fat mass and not simpler body mass index (BMI), because BMI leaves a portion of the obese population unrecognized. The aim is to evaluate the relationship between FM% and immune-inflammatory response, after 10th days in ICU.Methods: Prospective observational study in single cohort of 22 adult patients, affected by COVID-19 pneumonia and admitted to the Intensive Care Unit (ICU) and classified (10) lean and (12) obese, according to Percentage of Fat Mass (FM%) and age (De Lorenzo classification). Patients were analyzed at admission in ICU and at 10th day.Results: Obese have steatosis, impaired hepatic function, compromise immune response and higher inflammation. In addition, they have a reduced prognostic nutritional index (PNI), nutritional survival index for ICU patients.Conclusion: This is the first study evaluating FM% in COVID-19 patient. We underlined obese characteristic with likely poorly prognosis and an important misclassification of obesity. A not negligible number of patients with normal BMI could actually have an excess of adipose tissue and therefore have an unfavorable outcome such as an obese. Is fundamental personalized patients nutrition basing on disease phases.

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“…In addition to the large cohort of tumor samples tested, a small panel of patients where non-tumor tissue was extracted and tested was examined for ACE2 expression. Pathway analysis was performed using KEGG pathway colored mapping on Z-scores of fold change between groups 22 . All analyses were performed on deidenti ed, retrospective cases.…”

Section: Methodsmentioning

confidence: 99%

Pan-cancer analysis of RNA expression of ANGIOTENSIN-CONVERTING ENZYME II (ACE2) and cellular proteases reveals high variability and possible impact on COVID-19 clinical outcomes

Elliott

Saul

Zeng

et al. 2020

Preprint

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Patients with cancer demonstrate particularly poor outcomes from COVID-19. To provide information essential for understanding the biologic underpinnings of this association, we analyzed whole-transcriptome RNA expression data obtained from a large cohort of cancer patients to characterize expression of ACE2, TMPRSS2, and other proteases that are involved in viral attachment to and entry into target cells. We find substantial variability of expression of these factors across tumor types and identify subpopulations expressing ACE2 at very high levels. In some tumor types, especially in gastrointestinal cancers, expression of ACE2 and TMPRSS2 is highly correlated. Furthermore, we found infiltration with T-cell and natural killer (NK) cell infiltration to be particularly pronounced in ACE2-high tumors. These findings suggest that subsets of cancer patients exist with heightened susceptibility to SARS-CoV-2 infection in whom malignant tumors function as viral reservoir and possibly promote the frequently detrimental hyper-immune response in patients infected with this virus.

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Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19

Cited by 255 publications

References 30 publications

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract

Fat mass prevalence and influence on nutritional status in ICU COVID-19 patients

Pan-cancer analysis of RNA expression of ANGIOTENSIN-CONVERTING ENZYME II (ACE2) and cellular proteases reveals high variability and possible impact on COVID-19 clinical outcomes

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