# Blood Transcriptome Profiling Highlights the Role of Intestinal Bacterial Translocation in Severe COVID-19

## TL;DR

This study uses blood gene expression to show that severe COVID-19 is linked to intestinal bacterial translocation, offering new insights into disease severity.

## Contribution

The study identifies intestinal bacterial translocation as a novel driver of severe COVID-19 through blood transcriptome analysis.

## Key findings

- Severe COVID-19 patients showed enriched gene pathways related to bacterial molecules like LPS.
- Neutrophil levels increased while monocytes, CD8+ T cells, and NK cells decreased in severe cases.
- These immune cell changes suggest a link between severe disease and intestinal bacterial translocation.

## Abstract

COVID-19 has caused millions of deaths globally; however, the characterization of molecular biomarkers of severe disease remains of great scientific importance. The aim of this study was to capture the transcriptional differences of the whole blood gene expression between COVID-19 patients with mild and severe disease, using Next Generation Sequencing technologies, on admission and after 7 days. The genes which were differentially expressed in severe compared to mild patients were used for Gene Ontology (GO) enrichment analysis. Gene expression data were used to estimate the cell abundance of 22 immune cell types via digital cytometry. GO terms related to the response to molecules of bacterial origin, such as intestine-derived lipopolysaccharide (LPS), were enriched, among other dysregulated pathways, which are well described as paramount mechanisms of severe manifestations of COVID-19. The neutrophil population increased in patients with severe disease, whereas the monocyte, CD8+ T cell, and activated Natural Killer (NK) cell populations were depleted. These cell population dynamics are also indicative of severe COVID-19 and intestinal bacterial translocation. This study elucidates the molecular basis of severe COVID-19 and highlights intestinal bacterial translocation as a potential driver of severe disease.