Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome.
Adaptive Immunity
Adult
Aged
Bacteria
/ classification
Bacterial Load
Bronchoalveolar Lavage Fluid
/ immunology
COVID-19
/ immunology
Critical Illness
Female
Hospitalization
Humans
Immunity, Innate
Male
Microbiota
Middle Aged
Odds Ratio
Prognosis
Prospective Studies
Respiration, Artificial
Respiratory System
/ immunology
SARS-CoV-2
/ immunology
Viral Load
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
17
03
2021
accepted:
10
08
2021
pubmed:
2
9
2021
medline:
9
10
2021
entrez:
1
9
2021
Statut:
ppublish
Résumé
Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.
Identifiants
pubmed: 34465900
doi: 10.1038/s41564-021-00961-5
pii: 10.1038/s41564-021-00961-5
pmc: PMC8484067
mid: NIHMS1734100
doi:
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1245-1258Subventions
Organisme : NCI NIH HHS
ID : R01 CA159036
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016087
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK110014
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143861
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL125816
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI158997
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI140754
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA244775
Pays : United States
Organisme : NCI NIH HHS
ID : P20 CA252728
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI100853
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137336
Pays : United States
Commentaires et corrections
Type : UpdateOf
Type : UpdateOf
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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