TY - JOUR
T1 - Severe Dysbiosis and Specific Haemophilus and Neisseria Signatures as Hallmarks of the Oropharyngeal Microbiome in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients
AU - de Castilhos, Juliana
AU - Zamir, Eli
AU - Hippchen, Theresa
AU - Rohrbach, Roman
AU - Schmidt, Sabine
AU - Hengler, Silvana
AU - Schumacher, Hanna
AU - Neubauer, Melanie
AU - Kunz, Sabrina
AU - Mueller-Esch, Tonia
AU - Hiergeist, Andreas
AU - Gessner, Andre
AU - Khalid, Dina
AU - Gaiser, Rogier
AU - Cullin, Nyssa
AU - Papagiannarou, Stamatia M.
AU - Beuthien-Baumann, Bettina
AU - Kraemer, Alwin
AU - Bartenschlager, Ralf
AU - Jaeger, Dirk
AU - Mueller, Michael
AU - Herth, Felix
AU - Duerschmied, Daniel
AU - Schneider, Jochen
AU - Schmid, Roland M.
AU - Eberhardt, Johann F.
AU - Khodamoradi, Yascha
AU - Vehreschild, Maria J. G. T.
AU - Teufel, Andreas
AU - Ebert, Matthias P.
AU - Hau, Peter
AU - Salzberger, Bernd
AU - Schnitzler, Paul
AU - Poeck, Hendrik
AU - Elinav, Eran
AU - Merle, Uta
AU - Stein-Thoeringer, Christoph K.
N1 - The authors would like to thank the FightCovid@DKFZ initiative and the High Throughput Sequencing unit of the Genomics and Proteomics Core Facility at the German Cancer Research Center for providing sequencing service on Illumina NovaSeq 6000 instruments. Financial Support. This work was supported by a donation of the Ralph Lauren Foundation to R. B. and C. S. T. (12237). H. P. received funding by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)— grant number 395357507–SFB 1371; M. E. and A. T. were supported by the state of Baden-Wuerttemberg, Ministry of Science, Research and Arts ([Forum Gesundheitsstandort Baden-Wuerttemberg], Project BW-ZDFP) and by The Sino-German Center for Research Promotion (German Research Foundation (DFG) and the National Natural Science Foundation of China (NSFC), Project C-0012). Author Contributions. J. d. C., E. Z., T. H., and R. R. contributed equally. U. M. and C. S.-T. contributed equally. J. d. C., T. H., R. R., R. G., B. B-B., A. K., D. J., E. E., U. M., and C. S.-T. contributed to study concept and design. J. d. C., T. H., R. R., E. Z., S. S., S. H., H. S., M. N., S. K., T. M-E., A. H., Y. K., A. G., M. M., D. D., J. S., P. H., J. E., and C. S.-T. participated in data collection and analysis. J. d. C., D. K., N. C., R. B., F. H., R. S., M. V., A. T., M. E., B. S., H. P., E. E., and U. M. contributed to literature search, writing the article and data interpretation. J. d. C., E. Z., H. S., and C. S.-T. made figures and tables.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85137127096&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/cid/ciab902
DO - https://doi.org/10.1093/cid/ciab902
M3 - مقالة
C2 - 34694375
SN - 1058-4838
VL - 75
SP - E1063-E1071
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 1
ER -