Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19.

التفاصيل البيبلوغرافية
العنوان: Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19.
المؤلفون: Tsitsiklis A, Zha BS, Byrne A, DeVoe C, Rackaityte E, Levan S, Sunshine S, Mick E, Ghale R, Love C, Tarashansky AJ, Pisco A, Albright J, Jauregui A, Sarma A, Neff N, Serpa PH, Deiss TJ, Kistler A, Carrillo S, Ansel KM, Leligdowicz A, Christenson S, Detweiler A, Jones NG, Wu B, Darmanis S, Lynch SV, DeRisi JL, Matthay MA, Hendrickson CM, Kangelaris KN, Krummel MF, Woodruff PG, Erle DJ, Rosenberg O, Calfee CS, Langelier CR
مؤلفون مشاركون: COMET Consortium
المصدر: MedRxiv : the preprint server for health sciences [medRxiv] 2021 Nov 30. Date of Electronic Publication: 2021 Nov 30.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE
مستخلص: 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.
معلومات مُعتمدة: K08 HL163405 United States HL NHLBI NIH HHS; T32 GM007618 United States GM NIGMS NIH HHS; U19 AI077439 United States AI NIAID NIH HHS
تواريخ الأحداث: Date Created: 20210401 Latest Revision: 20240712
رمز التحديث: 20240712
مُعرف محوري في PubMed: PMC8010763
DOI: 10.1101/2021.03.23.21253487
PMID: 33791731
قاعدة البيانات: MEDLINE
الوصف
DOI:10.1101/2021.03.23.21253487