Severe Dysbiosis and Specific Haemophilus and Neisseria Signatures as Hallmarks of the Oropharyngeal Microbiome in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients.


Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
24 08 2022
Historique:
received: 19 07 2021
pubmed: 26 10 2021
medline: 30 8 2022
entrez: 25 10 2021
Statut: ppublish

Résumé

At the entry site of respiratory virus infections, the oropharyngeal microbiome has been proposed as a major hub integrating viral and host immune signals. Early studies suggested that infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with changes of the upper and lower airway microbiome, and that specific microbial signatures may predict coronavirus disease 2019 (COVID-19) illness. However, the results are not conclusive, as critical illness can drastically alter a patient's microbiome through multiple confounders. To study oropharyngeal microbiome profiles in SARS-CoV-2 infection, clinical confounders, and prediction models in COVID-19, we performed a multicenter, cross-sectional clinical study analyzing oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate, and severe COVID-19 (n = 322 participants). In contrast to mild infections, patients admitted to a hospital with moderate or severe COVID-19 showed dysbiotic microbial configurations, which were significantly pronounced in patients treated with broad-spectrum antibiotics, receiving invasive mechanical ventilation, or when sampling was performed during prolonged hospitalization. In contrast, specimens collected early after admission allowed us to segregate microbiome features predictive of hospital COVID-19 mortality utilizing machine learning models. Taxonomic signatures were found to perform better than models utilizing clinical variables with Neisseria and Haemophilus species abundances as most important features. In addition to the infection per se, several factors shape the oropharyngeal microbiome of severely affected COVID-19 patients and deserve consideration in the interpretation of the role of the microbiome in severe COVID-19. Nevertheless, we were able to extract microbial features that can help to predict clinical outcomes.

Sections du résumé

BACKGROUND
At the entry site of respiratory virus infections, the oropharyngeal microbiome has been proposed as a major hub integrating viral and host immune signals. Early studies suggested that infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with changes of the upper and lower airway microbiome, and that specific microbial signatures may predict coronavirus disease 2019 (COVID-19) illness. However, the results are not conclusive, as critical illness can drastically alter a patient's microbiome through multiple confounders.
METHODS
To study oropharyngeal microbiome profiles in SARS-CoV-2 infection, clinical confounders, and prediction models in COVID-19, we performed a multicenter, cross-sectional clinical study analyzing oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate, and severe COVID-19 (n = 322 participants).
RESULTS
In contrast to mild infections, patients admitted to a hospital with moderate or severe COVID-19 showed dysbiotic microbial configurations, which were significantly pronounced in patients treated with broad-spectrum antibiotics, receiving invasive mechanical ventilation, or when sampling was performed during prolonged hospitalization. In contrast, specimens collected early after admission allowed us to segregate microbiome features predictive of hospital COVID-19 mortality utilizing machine learning models. Taxonomic signatures were found to perform better than models utilizing clinical variables with Neisseria and Haemophilus species abundances as most important features.
CONCLUSIONS
In addition to the infection per se, several factors shape the oropharyngeal microbiome of severely affected COVID-19 patients and deserve consideration in the interpretation of the role of the microbiome in severe COVID-19. Nevertheless, we were able to extract microbial features that can help to predict clinical outcomes.

Identifiants

pubmed: 34694375
pii: 6409876
doi: 10.1093/cid/ciab902
pmc: PMC8586732
doi:

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1063-e1071

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Auteurs

Juliana de Castilhos (J)

German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.
Vale do Rio dos Sinos University (UNISINOS), Sao Leopoldo, Brazil.

Eli Zamir (E)

German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.

Theresa Hippchen (T)

Department of Gastroenterology and Infectious Diseases, University Clinic Heidelberg, Heidelberg, Germany.

Roman Rohrbach (R)

German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.

Sabine Schmidt (S)

German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.

Silvana Hengler (S)

German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.

Hanna Schumacher (H)

German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.

Melanie Neubauer (M)

Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Sabrina Kunz (S)

Department of Internal Medicine III, University Clinic Regensburg, Regensburg, Germany.

Tonia Müller-Esch (T)

Department of Internal Medicine III, University Clinic Regensburg, Regensburg, Germany.

Andreas Hiergeist (A)

Institute of Clinical Microbiology and Hygiene, University Clinic Regensburg, Regensburg, Germany.

André Gessner (A)

Institute of Clinical Microbiology and Hygiene, University Clinic Regensburg, Regensburg, Germany.

Dina Khalid (D)

Department of Virology, University Clinic Heidelberg, Heidelberg, Germany.

Rogier Gaiser (R)

German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.

Nyssa Cullin (N)

German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.

Stamatia M Papagiannarou (SM)

German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.

Bettina Beuthien-Baumann (B)

German Cancer Research Center (DKFZ), Research Division Radiology, Heidelberg, Germany.

Alwin Krämer (A)

German Cancer Research Center (DKFZ), Research Division Molecular Hematology/Oncology, Heidelberg, Germany.

Ralf Bartenschlager (R)

Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
German Cancer Research Center (DKFZ), Research Division Virus-associated Carcinogenesis, Heidelberg.

Dirk Jäger (D)

National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany.

Michael Müller (M)

Thoraxklinik and Translational Lung Research Center, Heidelberg University, Heidelberg, Germany.

Felix Herth (F)

Thoraxklinik and Translational Lung Research Center, Heidelberg University, Heidelberg, Germany.

Daniel Duerschmied (D)

Department of Internal Medicine III, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Jochen Schneider (J)

Department of Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Roland M Schmid (RM)

Department of Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Johann F Eberhardt (JF)

Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.

Yascha Khodamoradi (Y)

Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.

Maria J G T Vehreschild (MJGT)

Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.
German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.

Andreas Teufel (A)

Department of Medicine II, Section of Hepatology, University Medical Center Mannheim, University of Heidelberg, Mannheim, and Center for Preventive Medicine and Digital Health Baden-Württemberg, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Matthias P Ebert (MP)

Department of Medicine II, Section of Hepatology, University Medical Center Mannheim, University of Heidelberg, Mannheim, and Center for Preventive Medicine and Digital Health Baden-Württemberg, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Peter Hau (P)

Wilhelm Sander-NeuroOncology Unit and Department of Neurology, University Clinic Regensburg, Regensburg, Germany.

Bernd Salzberger (B)

Department of Infectious Disease, University Clinic Regensburg, Regensburg, Germany.

Paul Schnitzler (P)

Department of Virology, University Clinic Heidelberg, Heidelberg, Germany.

Hendrik Poeck (H)

Department of Internal Medicine III, University Clinic Regensburg, Regensburg, Germany.
National Center for Tumor Diseases (NCT) WERA.

Eran Elinav (E)

German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.
Weizmann Institute of Science, Rehovot, Israel.

Uta Merle (U)

Department of Gastroenterology and Infectious Diseases, University Clinic Heidelberg, Heidelberg, Germany.

Christoph K Stein-Thoeringer (CK)

German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.
National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany.

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