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| 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
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| 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.
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| 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).
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| Contributor(s) |
García-Hidalgo MC, Peláez R, de Gonzalo-Calvo D, Larráyoz IM |
| Citation(s) |
36058144 |
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| Submission date |
Mar 27, 2023 |
| Last update date |
Apr 22, 2024 |
| Contact name |
David de Gonzalo-Calvo |
| E-mail(s) |
dgonzalo@irblleida.cat
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| Phone |
973702201
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| Organization name |
IRBLleida
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| Street address |
Rovira Roure 80
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| City |
Lleida |
| State/province |
Lleida |
| ZIP/Postal code |
25196 |
| Country |
Spain |
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| Platforms (1) |
| GPL18460 |
Illumina HiSeq 1500 (Homo sapiens) |
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| Samples (50)
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| GSM7118732 |
WB, post-COVID-19, control MC1_8 |
| GSM7118733 |
WB, post-COVID-19, control MC1_10 |
| GSM7118734 |
WB, post-COVID-19, control MC1_101 |
| GSM7118735 |
WB, post-COVID-19, sequela MC1_11 |
| GSM7118736 |
WB, post-COVID-19, control MC1_12 |
| GSM7118737 |
WB, post-COVID-19, sequela MC1_14 |
| GSM7118738 |
WB, post-COVID-19, sequela MC1_15 |
| GSM7118739 |
WB, post-COVID-19, control MC1_16 |
| GSM7118740 |
WB, post-COVID-19, sequela MC1_25 |
| GSM7118741 |
WB, post-COVID-19, control MC1_26 |
| GSM7118742 |
WB, post-COVID-19, control MC1_30 |
| GSM7118743 |
WB, post-COVID-19, control MC1_31 |
| GSM7118744 |
WB, post-COVID-19, control MC1_32 |
| GSM7118745 |
WB, post-COVID-19, control MC1_34 |
| GSM7118746 |
WB, post-COVID-19, control MC1_36 |
| GSM7118747 |
WB, post-COVID-19, control MC1_37 |
| GSM7118748 |
WB, post-COVID-19, sequela MC1_38 |
| GSM7118749 |
WB, post-COVID-19, control MC1_39 |
| GSM7118750 |
WB, post-COVID-19, sequela MC1_42 |
| GSM7118751 |
WB, post-COVID-19, control MC1_44 |
| GSM7118752 |
WB, post-COVID-19, sequela MC1_45 |
| GSM7118753 |
WB, post-COVID-19, control MC1_46 |
| GSM7118754 |
WB, post-COVID-19, control MC1_47 |
| GSM7118755 |
WB, post-COVID-19, control MC1_49 |
| GSM7118756 |
WB, post-COVID-19, sequela MC1_56 |
| GSM7118757 |
WB, post-COVID-19, control MC1_57 |
| GSM7118758 |
WB, post-COVID-19, sequela MC1_58 |
| GSM7118759 |
WB, post-COVID-19, sequela MC1_59 |
| GSM7118760 |
WB, post-COVID-19, sequela MC1_65 |
| GSM7118761 |
WB, post-COVID-19, control MC1_66 |
| GSM7118762 |
WB, post-COVID-19, control MC1_67 |
| GSM7118763 |
WB, post-COVID-19, control MC1_69 |
| GSM7118764 |
WB, post-COVID-19, sequela MC1_71 |
| GSM7118765 |
WB, post-COVID-19, control MC1_72 |
| GSM7118766 |
WB, post-COVID-19, sequela MC1_75 |
| GSM7118767 |
WB, post-COVID-19, sequela MC1_76 |
| GSM7118768 |
WB, post-COVID-19, control MC1_78 |
| GSM7118769 |
WB, post-COVID-19, control MC1_79 |
| GSM7118770 |
WB, post-COVID-19, sequela MC1_81 |
| GSM7118771 |
WB, post-COVID-19, control MC1_84 |
| GSM7118772 |
WB, post-COVID-19, control MC1_85 |
| GSM7118773 |
WB, post-COVID-19, sequela MC1_86 |
| GSM7118774 |
WB, post-COVID-19, sequela MC1_88 |
| GSM7118775 |
WB, post-COVID-19, control MC1_89 |
| GSM7118776 |
WB, post-COVID-19, control MC1_93 |
| GSM7118777 |
WB, post-COVID-19, control MC1_96 |
| GSM7118778 |
WB, post-COVID-19, control MC1_99 |
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| Relations |
| BioProject |
PRJNA949252 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE228320_Counts_Normalized_postCOVID.txt.gz |
6.0 Mb |
(ftp)(http) |
TXT |
| GSE228320_Raw_counts.txt.gz |
1.7 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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