Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19.
Alexandra TsitsiklisBeth ZhaAshley ByrneCatherine DeVoeSophia LevanElze RackaityteSara SunshineEran MickRajani GhaleAlejandra JaureguiNorma F NeffAartik SarmaPaula SerpaThomas DeissAmy KistlerSidney CarrilloKarl Mark AnselAleksandra LeligdowiczStephanie ChristensonNorman JonesBing WuSpyros DarmanisMichael A MatthaySusan V LynchJoseph DeRisiComet ConsortiumCarolyn HendricksonKirsten KangelarisMatthew F KrummelPrescott WoodruffDavid J ErleOren S RosenbergCarolyn CalfeeCharles R LangelierPublished in: Research square (2021)
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.
Keyphrases
- coronavirus disease
- sars cov
- single cell
- respiratory tract
- respiratory syndrome coronavirus
- rna seq
- immune response
- gene expression
- high throughput
- mental health
- cardiac arrest
- transcription factor
- type diabetes
- hiv infected
- genome wide
- intensive care unit
- toll like receptor
- acute respiratory distress syndrome
- multidrug resistant
- cross sectional
- cardiovascular events
- coronary artery disease
- heat shock
- community acquired pneumonia
- heat shock protein