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Impaired antibacterial immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19
Alexandra Tsitsiklis; Beth Shoshana Zha; Ashley Byrne; Catherine Devoe; Elze Rackaityte; Sophia Levan; Sara Sunshine; Eran Mick; Rajani Ghale; Christina Love; Alexander J Tarashansky; Angela Pisco; Jack Albright; Alejandra Jauregui; Aartik Sarma; Norma Neff; Paula Hayakawa Serpa; Thomas J. Deiss; Amy Kistler; Sidney Carrillo; K. Mark Ansel; Aleksandra Leligdowicz; Stephanie Christenson; Norman Jones; Bing Wu; Spyros Darmanis; Michael M Matthay; Susan V Lynch; Joseph L. DeRisi; - COMET Consortium; Carolyn M. Hendrickson; Kristen N. Kangelaris; Matthew F. Krummel; Prescott G. Woodruff; David J. Earle; Oren Rosenberg; Carolyn S. Calfee; Charles R. Langelier.
Afiliação
  • Alexandra Tsitsiklis; University of California, San Francisco
  • Beth Shoshana Zha; University of California, San Francisco
  • Ashley Byrne; Chan Zuckerberg Biohub
  • Catherine Devoe; University of California, San Francisco
  • Elze Rackaityte; University of California, San Francisco
  • Sophia Levan; University of California, San Francisco
  • Sara Sunshine; University of California, San Francisco
  • Eran Mick; University of California, San Francisco, Chan Zuckerberg Biohub
  • Rajani Ghale; University of California, San Francisco
  • Christina Love; University of California San Francisco
  • Alexander J Tarashansky; Chan Zuckerberg Biohub
  • Angela Pisco; Chan Zuckerberg Biohub
  • Jack Albright; Chan Zuckerberg Biohub
  • Alejandra Jauregui; University of California, San Francisco
  • Aartik Sarma; University of California, San Francisco
  • Norma Neff; Chan Zuckerberg Biohub
  • Paula Hayakawa Serpa; University of California, San Francisco
  • Thomas J. Deiss; University of California, San Francisco
  • Amy Kistler; Chan Zuckerberg Biohub
  • Sidney Carrillo; University of California, San Francisco
  • K. Mark Ansel; University of California, San Francisco
  • Aleksandra Leligdowicz; University of California, San Francisco
  • Stephanie Christenson; University of California, San Francisco
  • Norman Jones; University of California, San Francisco
  • Bing Wu; Genentech
  • Spyros Darmanis; Genentech
  • Michael M Matthay; University of California, San Francisco
  • Susan V Lynch; University of California, San Francisco
  • Joseph L. DeRisi; UCSF, Chan Zuckerberg Biohub
  • - COMET Consortium;
  • Carolyn M. Hendrickson; University of California, San Francisco
  • Kristen N. Kangelaris; University of California, San Francisco
  • Matthew F. Krummel; University of California, San Francisco
  • Prescott G. Woodruff; University of California, San Francisco
  • David J. Earle; University of California, San Francisco
  • Oren Rosenberg; University of California, San Francisco
  • Carolyn S. Calfee; University of California, San Francisco
  • Charles R. Langelier; University of California, San Francisco
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21253487
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.
Licença
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Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Tipo de estudo: Estudo prognóstico Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Preprint
Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Tipo de estudo: Estudo prognóstico Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Preprint
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