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Single-cell RNA-sequencing reveals dysregulation of molecular programs associated with SARS-CoV-2 severity and outcomes in patients with chronic lung disease (preprint)
biorxiv; 2020.
Preprint
em Inglês
| bioRxiv | ID: ppzbmed-10.1101.2020.10.20.347187
ABSTRACT
Rationale Patients with chronic lung disease have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Objectives:
To identify molecular characteristics of diseased lung epithelial and immune cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases.Methods:
We analyzed the transcriptomes of 605,904 single cells isolated from healthy (79 samples) and diseased human lungs (31 chronic obstructive pulmonary disease (COPD), 82 idiopathic pulmonary fibrosis (IPF) and 18 non-IPF interstitial lung disease samples). Measurements and MainResults:
Cellular distribution and relative expression of SARS-CoV-2 entry factors (ACE2, TMPRSS2) was similar in disease and control lungs. Epithelial cells isolated from diseased lungs expressed higher levels of genes linked directly to efficiency of viral replication and the innate immune response. Unique ACE2-correlated gene sets were identified for each diagnosis group in the type II alveolar cells. Diseased lungs have a significant increase in the proportion of CD4, CD8 and NK cells compared to control lungs. Components of the interferon pathway, the IL6 cytokine pathway and the major histocompatibility complex (MHC) class II genes are upregulated in several diseased immune cell types. These differences in inflammatory gene expression programs highlight how chronic lung disease alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung.Conclusions:
Chronic lung disease is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence innate and adaptive immune responses to SARS-CoV-2 infection.
Texto completo:
Disponível
Coleções:
Preprints
Base de dados:
bioRxiv
Assunto principal:
Embolia Pulmonar
/
Doenças Pulmonares Intersticiais
/
Adenocarcinoma Bronquioloalveolar
/
Doença Pulmonar Obstrutiva Crônica
/
Fibrose Pulmonar Idiopática
/
COVID-19
/
Pneumopatias
Idioma:
Inglês
Ano de publicação:
2020
Tipo de documento:
Preprint
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