Impaired antibacterial immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19
Tsitsiklis, A.; Zha, B. S.; Byrne, A.; Devoe, C.; Levan, S.; Rackaityte, E.; Sunshine, S.; Mick, E.; Ghale, R.; Jauregui, A.; Sarma, A.; Neff, N.; Serpa, P. H.; Deiss, T. J.; Kistler, A.; Carrillo, S.; Ansel, K. M.; Leligdowicz, A.; Christenson, S.; Jones, N.; Wu, B.; Darmanis, S.; Matthay, M. M.; Lynch, S. V.; DeRisi, J. L.; COMET Consortium, ; Hendrickson, C. M.; Kangelaris, K. N.; Krummel, M. F.; Woodruff, P. G.; Earle, D. J.; Rosenberg, O.; Calfee, C. S.; Langelier, C. R.
Show abstract
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.
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