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Severe Dysbiosis and Specific Haemophilus and Neisseria Signatures as Hallmarks of the Oropharyngeal Microbiome in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients.
de Castilhos, Juliana; Zamir, Eli; Hippchen, Theresa; Rohrbach, Roman; Schmidt, Sabine; Hengler, Silvana; Schumacher, Hanna; Neubauer, Melanie; Kunz, Sabrina; Müller-Esch, Tonia; Hiergeist, Andreas; Gessner, André; Khalid, Dina; Gaiser, Rogier; Cullin, Nyssa; Papagiannarou, Stamatia M; Beuthien-Baumann, Bettina; Krämer, Alwin; Bartenschlager, Ralf; Jäger, Dirk; Müller, Michael; Herth, Felix; Duerschmied, Daniel; Schneider, Jochen; Schmid, Roland M; Eberhardt, Johann F; Khodamoradi, Yascha; Vehreschild, Maria J G T; Teufel, Andreas; Ebert, Matthias P; Hau, Peter; Salzberger, Bernd; Schnitzler, Paul; Poeck, Hendrik; Elinav, Eran; Merle, Uta; Stein-Thoeringer, Christoph K.
  • de Castilhos J; German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.
  • Zamir E; Vale do Rio dos Sinos University (UNISINOS), Sao Leopoldo, Brazil.
  • Hippchen T; German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.
  • Rohrbach R; Department of Gastroenterology and Infectious Diseases, University Clinic Heidelberg, Heidelberg, Germany.
  • Schmidt S; German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.
  • Hengler S; German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.
  • Schumacher H; German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.
  • Neubauer M; German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.
  • Kunz S; Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
  • Müller-Esch T; Department of Internal Medicine III, University Clinic Regensburg, Regensburg, Germany.
  • Hiergeist A; Department of Internal Medicine III, University Clinic Regensburg, Regensburg, Germany.
  • Gessner A; Institute of Clinical Microbiology and Hygiene, University Clinic Regensburg, Regensburg, Germany.
  • Khalid D; Institute of Clinical Microbiology and Hygiene, University Clinic Regensburg, Regensburg, Germany.
  • Gaiser R; Department of Virology, University Clinic Heidelberg, Heidelberg, Germany.
  • Cullin N; German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.
  • Papagiannarou SM; German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.
  • Beuthien-Baumann B; German Cancer Research Center (DKFZ), Research Division Microbiome and Cancer, Heidelberg, Germany.
  • Krämer A; German Cancer Research Center (DKFZ), Research Division Radiology, Heidelberg, Germany.
  • Bartenschlager R; German Cancer Research Center (DKFZ), Research Division Molecular Hematology/Oncology, Heidelberg, Germany.
  • Jäger D; Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
  • Müller M; German Cancer Research Center (DKFZ), Research Division Virus-associated Carcinogenesis, Heidelberg.
  • Herth F; National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany.
  • Duerschmied D; Thoraxklinik and Translational Lung Research Center, Heidelberg University, Heidelberg, Germany.
  • Schneider J; Thoraxklinik and Translational Lung Research Center, Heidelberg University, Heidelberg, Germany.
  • Schmid RM; Department of Internal Medicine III, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Eberhardt JF; Department of Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
  • Khodamoradi Y; Department of Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
  • Vehreschild MJGT; Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.
  • Teufel A; Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.
  • Ebert MP; Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany.
  • Hau P; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
  • Salzberger B; 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.
  • Schnitzler P; 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.
  • Poeck H; Wilhelm Sander-NeuroOncology Unit and Department of Neurology, University Clinic Regensburg, Regensburg, Germany.
  • Elinav E; Department of Infectious Disease, University Clinic Regensburg, Regensburg, Germany.
  • Merle U; Department of Virology, University Clinic Heidelberg, Heidelberg, Germany.
  • Stein-Thoeringer CK; Department of Internal Medicine III, University Clinic Regensburg, Regensburg, Germany.
Clin Infect Dis ; 75(1): e1063-e1071, 2022 Aug 24.
Article in English | MEDLINE | ID: covidwho-2017768
ABSTRACT

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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Microbiota / COVID-19 Type of study: Observational study / Prognostic study / Randomized controlled trials Limits: Adult / Humans Language: English Journal: Clin Infect Dis Journal subject: Communicable Diseases Year: 2022 Document Type: Article Affiliation country: Cid

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Microbiota / COVID-19 Type of study: Observational study / Prognostic study / Randomized controlled trials Limits: Adult / Humans Language: English Journal: Clin Infect Dis Journal subject: Communicable Diseases Year: 2022 Document Type: Article Affiliation country: Cid