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

Juliana de Castilhos, Eli Zamir, Theresa Hippchen, Roman Rohrbach, Sabine Schmidt, Silvana Hengler, Hanna Schumacher, Melanie Neubauer, Sabrina Kunz, Tonia Mueller-Esch, Andreas Hiergeist, Andre Gessner, Dina Khalid, Rogier Gaiser, Nyssa Cullin, Stamatia M. Papagiannarou, Bettina Beuthien-Baumann, Alwin Kraemer, Ralf Bartenschlager, Dirk JaegerMichael Mueller, Felix Herth, Daniel Duerschmied, Jochen Schneider, Roland M. Schmid, Johann F. Eberhardt, Yascha Khodamoradi, Maria J. G. T. Vehreschild, Andreas Teufel, Matthias P. Ebert, Peter Hau, Bernd Salzberger, Paul Schnitzler, Hendrik Poeck, Eran Elinav, Uta Merle, Christoph K. Stein-Thoeringer

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)E1063-E1071
JournalClinical Infectious Diseases
Volume75
Issue number1
DOIs
StatePublished - 1 Jul 2022

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

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