<scp>SARS</scp>‐CoV‐2 receptor<scp>ACE</scp>2 and<scp>TMPRSS</scp>2 are primarily expressed in bronchial transient secretory cells

Lukassen, Soeren; Chua, Robert Lorenz; Trefzer, Timo B.; Kahn, Nicolas; Schneider, Marc A.; Muley, Thomas; Winter, Hauke; Meister, Michael; Veith, Carmen; Boots, Agnes W.; Hennig, Bianca P.; Kreuter, Michael; Conrad, Christian; Eils, Roland

doi:10.15252/embj.20105114

Cited by 826 publications

(365 citation statements)

References 58 publications

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“…Unsupervised analysis identified 20 distinct cell clusters ( Figure 1A and Figure S1-S3), including epithelial (EPCAM+) and immune (PTPRC+) cell populations ( Figure S4). ACE2 and TMPRSS2 were primarily expressed in lung epithelial cells ( Figure 1B), in line with other studies 16,17 . Among lung epithelial populations, a relative high percentage of ACE2 or TMPRSS2 positive cells were shown in club, basal and ciliated cells which may act as primary target cells of SARS-CoV-2 infection ( Figure 1C).…”

Section: Lung Epithelial Cells Express Higher Ace2 In Covid-19 Patientssupporting

confidence: 92%

SARS-CoV-2 activates lung epithelia cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients by single-cell sequencing

Chen

Liu

et al. 2020

Preprint

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Objective: The outbreak of Coronavirus disease 2019 caused by SARS-CoV-2 infection has become a global health emergency. We aim to decipher SARS-CoV-2 infected cell types, the consequent host immune response and their interplay in the lung of COVID-19 patients. Design:We analyzed single-cell RNA sequencing (scRNA-seq) data of lung samples from 17 subjects (6 severe COVID-19 patients, 3 mild patients who recovered and 8 healthy controls). The expression of SARS-CoV-2 receptors (ACE2 and TMPRSS2) was examined among different cell types in the lung. The immune cells infiltration patterns, their gene expression profiles, and the interplay of immune cells and SARS-CoV-2 target cells were further investigated. Results: Compared to healthy controls, the overall ACE2 (receptor of SARS-CoV-2) expression was significantly higher in lung epithelial cells of COVID-19 patients, in particular in ciliated cell, club cell and basal cell. Comparative transcriptome analysis of these lung epithelial cells of COVID-19 patients and healthy controls identified that SARS-CoV-2 infection activated pro-inflammatory signaling including interferon pathway and cytokine signaling. Moreover, we identified dysregulation of immune response in patients with COVID-19. In severe COVID-19 patients, significantly higher neutrophil, but lower T and NK cells in lung were observed along with markedly increased cytokines (CCL2, CCL3, CCL4, CCL7, CCL3L1 and CCL4L2) compared with healthy controls as well as mild patients who recovered. The cytotoxic phenotypes were shown in lung T and NK cells of severe patients as evidenced by enhanced IFNγ, Granulysin, Granzyme B and Perforin expression. Moreover, SARS-CoV-2 infection altered the community interplay of lung epithelial cells and immune cells: the interaction between epithelial cells with macrophage, T and NK cell was stronger, but their interaction with neutrophils was lost in COVID-19 patients compared to healthy controls. : medRxiv preprint Conclusions: SARS-CoV-2 infection activates pro-inflammatory signaling in lung epithelial cells expressing ACE2 and causes dysregulation of immune response to release more pro-inflammatory cytokines. Moreover, SARS-CoV-2 infection breaks the interplay of lung epithelial cells and immune cells.

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Section: Lung Epithelial Cells Express Higher Ace2 In Covid-19 Patientssupporting

confidence: 92%

SARS-CoV-2 activates lung epithelia cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients by single-cell sequencing

Chen

Liu

et al. 2020

Preprint

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“…Our cross-tissue analysis substantially expands on our 45, 46,58,112 and others' [113][114][115] earlier efforts, allowing us to identify cell subsets across diverse tissues that may be implicated in virus transmission, pathogenesis, or both. Focusing on pathogenesis, in addition to key subsets in the lung, airways and gut, we identified ACE2 + cells that co-express either TMPRSS2 or CTSL in diverse organs, many of which have been associated with severe disease.…”

Section: Discussionmentioning

confidence: 99%

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

Muus

Luecken

Eraslan

et al. 2020

Preprint

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The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2 + TMPRSS2 + cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis.

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“…El mecanismo molecular subyacente a invasión celular del SARSCoV-2 se relaciona con su habilidad para unirse selectivamente a los receptores de la Enzima Convertidora de la Angiotensina 2 (ECA-2) de forma similar a como es conocido en el caso del SARS-CoV. Estos receptores presentan una alta expresión en las células epiteliales del sistema respiratorio e intestinal [29][30][31][32], pero también en el SNC, tanto en células gliales, como en neuronas, lo que hace del SNC una diana potencial del SARS-Cov-2 [33]. Además, estudios previos han demostrado la capacidad de este virus para causar muerte neuronal en ratones a través de la invasión del SNC por la lámina cribiforme del etmoides y la posterior invasión del neuroepitelio olfatorio [34].…”

Section: Capacidad Neuroinvasiva Directa Del Sars-cov2unclassified

Influencia de la infección SARS-CoV-2 sobre enfermedades neurodegenerativas y neuropsiquiátricas: ¿una pandemia demorada?

et al. 2020

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INTRODUCCIÓN: La infección por el coronavirus SARS-CoV2 originada en Diciembre de 2019 en la región china de Wuhan ha adquirido proporciones pandémicas. A día de hoy ha ocasionado de Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: a delayed pandemic?ABSTRACT Introduction: SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100 000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium-and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. Development:We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system.Conclusions: SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.

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SARS‐CoV‐2 receptorACE2 andTMPRSS2 are primarily expressed in bronchial transient secretory cells

Cited by 826 publications

References 58 publications

SARS-CoV-2 activates lung epithelia cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients by single-cell sequencing

SARS-CoV-2 activates lung epithelia cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients by single-cell sequencing

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

Influencia de la infección SARS-CoV-2 sobre enfermedades neurodegenerativas y neuropsiquiátricas: ¿una pandemia demorada?

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