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Impaired antibacterial immune signaling and changes in the lung microbiome precedes secondary bacterial pneumonia in COVID-19

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE168019 | GEO | 2021/03/03

REPOSITORIES: GEO

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Impaired antibacterial immune signaling and changes in the lung microbiome precedes secondary bacterial pneumonia in COVID-19 (scRNA-seq)

Project description:We preformed a systems biological assessment of lower respiratory tract host immune responses and microbiome dynamics in COVD-19 patients, using bulk RNA-sequencing, single-cell RNA sequencing, and techniques, and microbiome analysis. Are focus was on differential gene expression in severe COVID-19 patients who developed ventilator associated pneumonia (VAP) during their course versus severe COVID-19 patients who did not develop VAP. We found early impairment in antibacterial immune signaling in patients two or more weeks prior to the development of VAP, compared to COVID-19 patients who did not develop VAP. There was no signficant difference in viral load, but an association of disruption in lung microbiome by alpha and beta diversity metrics was also found.

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Impaired antibacterial immune signaling and changes in the lung microbiome precedes secondary bacterial pneumonia in COVID-19 (bulkRNA-seq)

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Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19.

Project description:Secondary bacterial infections, including ventilator-associated pneumonia (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections including in patients with coronavirus disease 2019 (COVID-19). Using a combination of tracheal aspirate bulk and single-cell RNA sequencing (scRNA-seq) we assessed lower respiratory tract immune responses and microbiome dynamics in 28 COVID-19 patients, 15 of whom developed VAP, and eight critically ill uninfected controls. Two days before VAP onset we observed a transcriptional signature of bacterial infection. Two weeks prior to VAP onset, following intubation, we observed a striking impairment in immune signaling in COVID-19 patients who developed VAP. Longitudinal metatranscriptomic analysis revealed disruption of lung microbiome community composition in patients with VAP, providing a connection between dysregulated immune signaling and outgrowth of opportunistic pathogens. These findings suggest that COVID-19 patients who develop VAP have impaired antibacterial immune defense detectable weeks before secondary infection onset.

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Impaired antibacterial immune signaling and changes in the lung microbiome precedes secondary bacterial pneumonia in COVID-19

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Impaired antibacterial immune signaling and changes in the lung microbiome precedes secondary bacterial pneumonia in COVID-19 (bulkRNA-seq)

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