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Series GSE228320 Query DataSets for GSE228320
Status Public on Mar 28, 2023
Title Whole blood transcriptional profiling of pulmonary functional sequelae in ARDS- secondary to SARS-CoV-2 infection
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Up to 80% of patients surviving acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection present persistent anomalies in pulmonary function after hospital discharge. There is a limited understanding of the mechanistic pathways linked to post-acute pulmonary sequelae.
Our main goal was to identify the molecular underpinnings associated with severe lung diffusion involvement in survivors of SARS-CoV-2-induced ARDS.
Survivors attended to a complete pulmonary evaluation 3 months after hospital discharge. RNA sequencing (RNA-seq) was performed using Illumina technology in whole-blood samples from 50 patients with moderate to severe diffusion impairment (DLCO<60%) and age- and sex-matched individuals with mild-normal lung function (DLCO≥60%). A transcriptomic signature for optimal classification was constructed using random forest. Transcriptomic data were analyzed for biological pathway enrichment, cellular deconvolution, cell/tissue-specific gene expression and candidate drugs.
RNA-seq identified 1357 differentially expressed transcripts. A model composed of 14 mRNAs allowed the optimal discrimination of survivors with severe diffusion impairment (AUC=0.979). Hallmarks of lung sequelae involved cell death signaling, cytoskeleton reorganization, cell growth and differentiation and the immune response. Resting natural killer (NK) cells were the most important immune cell subtype for the prediction of severe diffusion impairment. Components of the signature correlated with neutrophil, lymphocyte and monocyte counts. A variable expression profile of the transcripts was observed in lung cell subtypes and bodily tissues. One upregulated gene, TUBB4A, constitutes a target for FDA-approved drugs.
This work defines the transcriptional programme associated with post-acute pulmonary sequelae and provides novel insights for targeted interventions and biomarker development.
 
Overall design Comparative gene expression profiling analysis of RNAseq data from whole blood from survivors of COVID-19-driven ARDS with moderate-to-severe functional pulmonary sequelae (DLCO<60% of predicted; group of study) and with mild or absence of functional pulmonary sequelae (DLCO≥60% of predicted; control group).
 
Contributor(s) García-Hidalgo MC, Peláez R, de Gonzalo-Calvo D, Larráyoz IM
Citation(s) 36058144
Submission date Mar 27, 2023
Last update date Apr 05, 2024
Contact name David de Gonzalo-Calvo
E-mail(s) dgonzalo@irblleida.cat
Phone 973702201
Organization name IRBLleida
Street address Rovira Roure 80
City Lleida
State/province Lleida
ZIP/Postal code 25196
Country Spain
 
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (50)
GSM7118729 WB, post-COVID-19, control MC1_1
GSM7118730 WB, post-COVID-19, control MC1_4
GSM7118731 WB, post-COVID-19, sequela MC1_7
Relations
BioProject PRJNA949252

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE228320_Counts_Normalized_postCOVID.txt.gz 6.0 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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