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High-Throughput Transcriptome Analysis for Investigating Host-Pathogen Interactions
Published on: March 5, 2022
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Transcriptomic clustering of critically ill COVID-19 patients
Cecilia López-Martínez1,2,3, Paula Martín-Vicente1,2,3, Juan Gómez de Oña1,4,5
1Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.
The European Respiratory Journal
|September 14, 2022
Summary
Transcriptomics identified two distinct patient groups in severe coronavirus disease 2019 (COVID-19) based on gene expression. These endotypes have different responses to steroids and varying intensive care unit (ICU) outcomes, guiding personalized COVID-19 treatment.
Area of Science:
- Molecular biology
- Immunology
- Infectious diseases
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a severe illness with high mortality.
- Systemic inflammation and host responses are key in COVID-19 pathogenesis, and modulating these responses can improve outcomes.
Purpose of the Study:
- To investigate distinct host response patterns in critically ill COVID-19 patients using transcriptomics.
- To identify patient endotypes for personalized COVID-19 therapy.
Main Methods:
- Peripheral blood transcriptomes from 56 critically ill COVID-19 patients were analyzed using unsupervised clustering.
- Gene expression, circulating microRNAs, and clinical data were compared between clusters.
- A transcriptomic signature was developed and validated in external cohorts.
Main Results:
- Two transcriptomic clusters emerged, characterized by interferon-related or immune checkpoint gene expression.
- Steroids demonstrated cluster-specific effects on lymphocyte and B-cell activation.
- These distinct profiles correlated with different intensive care unit (ICU) outcomes, despite similar initial clinical presentations.
Conclusions:
- Transcriptomics can identify distinct patient endotypes in severe COVID-19.
- These findings highlight different pathogenetic mechanisms and potential for personalized treatment strategies in COVID-19.

