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Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19.
Tsitsiklis, Alexandra; Zha, Beth Shoshana; Byrne, Ashley; Devoe, Catherine; Levan, Sophia; Rackaityte, Elze; Sunshine, Sara; Mick, Eran; Ghale, Rajani; Jauregui, Alejandra; Sarma, Aartik; Neff, Norma; Serpa, Paula Hayakawa; Deiss, Thomas J; Kistler, Amy; Carrillo, Sidney; Ansel, K Mark; Leligdowicz, Aleksandra; Christenson, Stephanie; Jones, Norman; Wu, Bing; Darmanis, Spyros; Matthay, Michael A; Lynch, Susan V; DeRisi, Joseph L; Hendrickson, Carolyn M; Kangelaris, Kirsten N; Krummel, Matthew F; Woodruff, Prescott G; Erle, David J; Rosenberg, Oren; Calfee, Carolyn S; Langelier, Charles R.
Afiliación
  • Tsitsiklis A; Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
  • Zha BS; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Byrne A; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Devoe C; Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
  • Levan S; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Rackaityte E; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA.
  • Sunshine S; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA.
  • Mick E; Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
  • Ghale R; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Jauregui A; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Sarma A; Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
  • Neff N; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Serpa PH; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Deiss TJ; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Kistler A; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Carrillo S; Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
  • Ansel KM; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Leligdowicz A; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Christenson S; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Jones N; Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.
  • Wu B; Sandler Asthma Basic Research Center, University of California, San Francisco, CA, USA.
  • Darmanis S; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Matthay MA; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Lynch SV; Department of Experimental Medicine, University of California, San Francisco, CA, USA.
  • DeRisi JL; Genentech, Inc. San Francisco, CA, USA.
  • Hendrickson CM; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Kangelaris KN; Department of Gastroenterology, University of California, San Francisco, CA, USA.
  • Krummel MF; Benioff Center for Microbiome Medicine, University of California, San Francisco, CA, USA.
  • Woodruff PG; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Erle DJ; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA.
  • Calfee CS; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Langelier CR; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Res Sq ; 2021 Apr 23.
Article en En | MEDLINE | ID: mdl-34013247
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 (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.
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Texto completo: 1 Banco de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos