RESUMO
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 we assessed lower respiratory tract immune responses and microbiome dynamics in 23 COVID-19 patients, 10 of whom developed VAP, and eight critically ill uninfected controls. At a median of three days (range: 2-4 days) before VAP onset we observed a transcriptional signature of bacterial infection. At a median of 15 days prior to VAP onset (range: 8-38 days), 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.
RESUMO
We performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with ARDS from COVID-19 or other etiologies, or without ARDS. We found no evidence of cytokine storm but instead observed complex host response dysregulation driven by genes with non-canonical roles in inflammation and immunity that were predicted to be modulated by dexamethasone. Compared to other viral ARDS, COVID-19 was characterized by impaired interferon-stimulated gene expression.
