Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19
| Autor: | Alexandra Tsitsiklis, Beth Zha, Ashley Byrne, Catherine DeVoe, Sophia Levan, Elze Rackaityte, Sara Sunshine, Eran Mick, Rajani Ghale, Alejandra Jauregui, Norma Neff, Aartik Sarma, Paula Serpa, Thomas Deiss, Amy Kistler, Sidney Carrillo, K. Mark Ansel, Aleksandra Leligdowicz, Stephanie Christenson, Norman Jones, Bing Wu, Spyros Darmanis, Michael Matthay, Susan Lynch, Joseph DeRisi, COMET Consortium, Carolyn Hendrickson, Kirsten Kangelaris, Matthew Krummel, Prescott Woodruff, David Erle, Oren Rosenberg, Carolyn Calfee, Charles Langelier |
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| Rok vydání: | 2021 |
| Předmět: |
metagenomics
Lung microbiome SARS-CoV-2 business.industry Secondary infection medicine.medical_treatment COVID-19 bacterial infections and mycoses medicine.disease Article respiratory tract diseases Pneumonia medicine.anatomical_structure Immune system scRNA-seq Immunology medicine VAP Intubation Microbiome Respiratory system business secondary bacterial pneumonia Respiratory tract |
| Zdroj: | Research Square article-version (status) pre article-version (number) 1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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