Oropharyngeal microbiome profiled at admission is predictive of the need for respiratory support among COVID-19 patients

The oropharyngeal microbiome, the collective genomes of the community of microorganisms that colonizes the upper respiratory tract, is thought to influence the clinical course of infection by respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative a...

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Main Authors: Evan S. Bradley, Abigail L. Zeamer, Vanni Bucci, Lindsey Cincotta, Marie-Claire Salive, Protiva Dutta, Shafik Mutaawe, Otuwe Anya, Christopher Tocci, Ann Moormann, Doyle V. Ward, Beth A. McCormick, John P. Haran
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2022.1009440/full
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author Evan S. Bradley
Evan S. Bradley
Abigail L. Zeamer
Abigail L. Zeamer
Vanni Bucci
Vanni Bucci
Lindsey Cincotta
Marie-Claire Salive
Protiva Dutta
Shafik Mutaawe
Otuwe Anya
Christopher Tocci
Ann Moormann
Doyle V. Ward
Doyle V. Ward
Beth A. McCormick
Beth A. McCormick
John P. Haran
John P. Haran
John P. Haran
author_facet Evan S. Bradley
Evan S. Bradley
Abigail L. Zeamer
Abigail L. Zeamer
Vanni Bucci
Vanni Bucci
Lindsey Cincotta
Marie-Claire Salive
Protiva Dutta
Shafik Mutaawe
Otuwe Anya
Christopher Tocci
Ann Moormann
Doyle V. Ward
Doyle V. Ward
Beth A. McCormick
Beth A. McCormick
John P. Haran
John P. Haran
John P. Haran
author_sort Evan S. Bradley
collection DOAJ
description The oropharyngeal microbiome, the collective genomes of the community of microorganisms that colonizes the upper respiratory tract, is thought to influence the clinical course of infection by respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Infectious Disease 2019 (COVID-19). In this study, we examined the oropharyngeal microbiome of suspected COVID-19 patients presenting to the Emergency Department and an inpatient COVID-19 unit with symptoms of acute COVID-19. Of 115 initially enrolled patients, 50 had positive molecular testing for COVID-19+ and had symptom duration of 14 days or less. These patients were analyzed further as progression of disease could most likely be attributed to acute COVID-19 and less likely a secondary process. Of these, 38 (76%) went on to require some form of supplemental oxygen support. To identify functional patterns associated with respiratory illness requiring respiratory support, we applied an interpretable random forest classification machine learning pipeline to shotgun metagenomic sequencing data and select clinical covariates. When combined with clinical factors, both species and metabolic pathways abundance-based models were found to be highly predictive of the need for respiratory support (F1-score 0.857 for microbes and 0.821 for functional pathways). To determine biologically meaningful and highly predictive signals in the microbiome, we applied the Stable and Interpretable RUle Set to the output of the models. This analysis revealed that low abundance of two commensal organisms, Prevotella salivae or Veillonella infantium (< 4.2 and 1.7% respectively), and a low abundance of a pathway associated with LPS biosynthesis (< 0.1%) were highly predictive of developing the need for acute respiratory support (82 and 91.4% respectively). These findings suggest that the composition of the oropharyngeal microbiome in COVID-19 patients may play a role in determining who will suffer from severe disease manifestations.
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spelling doaj.art-8c7ffc98f7c34464bed0fbf1b0da6e512022-12-22T03:23:56ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-09-011310.3389/fmicb.2022.10094401009440Oropharyngeal microbiome profiled at admission is predictive of the need for respiratory support among COVID-19 patientsEvan S. Bradley0Evan S. Bradley1Abigail L. Zeamer2Abigail L. Zeamer3Vanni Bucci4Vanni Bucci5Lindsey Cincotta6Marie-Claire Salive7Protiva Dutta8Shafik Mutaawe9Otuwe Anya10Christopher Tocci11Ann Moormann12Doyle V. Ward13Doyle V. Ward14Beth A. McCormick15Beth A. McCormick16John P. Haran17John P. Haran18John P. Haran19Department of Emergency Medicine, UMass Memorial Medical Center, Worcester, MA, United StatesProgram in Microbiome Dynamics, University of Massachusetts Medical School, Worcester, MA, United StatesProgram in Microbiome Dynamics, University of Massachusetts Medical School, Worcester, MA, United StatesDepartment of Microbiology and Physiologic Systems, University of Massachusetts Medical School, Worcester, MA, United StatesProgram in Microbiome Dynamics, University of Massachusetts Medical School, Worcester, MA, United StatesDepartment of Microbiology and Physiologic Systems, University of Massachusetts Medical School, Worcester, MA, United StatesDepartment of Emergency Medicine, UMass Memorial Medical Center, Worcester, MA, United StatesDepartment of Emergency Medicine, UMass Memorial Medical Center, Worcester, MA, United StatesDepartment of Emergency Medicine, UMass Memorial Medical Center, Worcester, MA, United StatesDepartment of Emergency Medicine, UMass Memorial Medical Center, Worcester, MA, United StatesDepartment of Emergency Medicine, UMass Memorial Medical Center, Worcester, MA, United StatesDepartment of Biology and Biotechnology, Worcester Polytechnique Institute, Worcester, MA, United StatesDepartment of Medicine, University of Massachusetts Medical School, Worcester, MA, United StatesProgram in Microbiome Dynamics, University of Massachusetts Medical School, Worcester, MA, United StatesDepartment of Microbiology and Physiologic Systems, University of Massachusetts Medical School, Worcester, MA, United StatesProgram in Microbiome Dynamics, University of Massachusetts Medical School, Worcester, MA, United StatesDepartment of Microbiology and Physiologic Systems, University of Massachusetts Medical School, Worcester, MA, United StatesDepartment of Emergency Medicine, UMass Memorial Medical Center, Worcester, MA, United StatesProgram in Microbiome Dynamics, University of Massachusetts Medical School, Worcester, MA, United StatesDepartment of Microbiology and Physiologic Systems, University of Massachusetts Medical School, Worcester, MA, United StatesThe oropharyngeal microbiome, the collective genomes of the community of microorganisms that colonizes the upper respiratory tract, is thought to influence the clinical course of infection by respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Infectious Disease 2019 (COVID-19). In this study, we examined the oropharyngeal microbiome of suspected COVID-19 patients presenting to the Emergency Department and an inpatient COVID-19 unit with symptoms of acute COVID-19. Of 115 initially enrolled patients, 50 had positive molecular testing for COVID-19+ and had symptom duration of 14 days or less. These patients were analyzed further as progression of disease could most likely be attributed to acute COVID-19 and less likely a secondary process. Of these, 38 (76%) went on to require some form of supplemental oxygen support. To identify functional patterns associated with respiratory illness requiring respiratory support, we applied an interpretable random forest classification machine learning pipeline to shotgun metagenomic sequencing data and select clinical covariates. When combined with clinical factors, both species and metabolic pathways abundance-based models were found to be highly predictive of the need for respiratory support (F1-score 0.857 for microbes and 0.821 for functional pathways). To determine biologically meaningful and highly predictive signals in the microbiome, we applied the Stable and Interpretable RUle Set to the output of the models. This analysis revealed that low abundance of two commensal organisms, Prevotella salivae or Veillonella infantium (< 4.2 and 1.7% respectively), and a low abundance of a pathway associated with LPS biosynthesis (< 0.1%) were highly predictive of developing the need for acute respiratory support (82 and 91.4% respectively). These findings suggest that the composition of the oropharyngeal microbiome in COVID-19 patients may play a role in determining who will suffer from severe disease manifestations.https://www.frontiersin.org/articles/10.3389/fmicb.2022.1009440/fulloropharyngeal microbiomeCOVID-19SARS-CoV-2random forest classificationcommensal organismsPrevotella
spellingShingle Evan S. Bradley
Evan S. Bradley
Abigail L. Zeamer
Abigail L. Zeamer
Vanni Bucci
Vanni Bucci
Lindsey Cincotta
Marie-Claire Salive
Protiva Dutta
Shafik Mutaawe
Otuwe Anya
Christopher Tocci
Ann Moormann
Doyle V. Ward
Doyle V. Ward
Beth A. McCormick
Beth A. McCormick
John P. Haran
John P. Haran
John P. Haran
Oropharyngeal microbiome profiled at admission is predictive of the need for respiratory support among COVID-19 patients
Frontiers in Microbiology
oropharyngeal microbiome
COVID-19
SARS-CoV-2
random forest classification
commensal organisms
Prevotella
title Oropharyngeal microbiome profiled at admission is predictive of the need for respiratory support among COVID-19 patients
title_full Oropharyngeal microbiome profiled at admission is predictive of the need for respiratory support among COVID-19 patients
title_fullStr Oropharyngeal microbiome profiled at admission is predictive of the need for respiratory support among COVID-19 patients
title_full_unstemmed Oropharyngeal microbiome profiled at admission is predictive of the need for respiratory support among COVID-19 patients
title_short Oropharyngeal microbiome profiled at admission is predictive of the need for respiratory support among COVID-19 patients
title_sort oropharyngeal microbiome profiled at admission is predictive of the need for respiratory support among covid 19 patients
topic oropharyngeal microbiome
COVID-19
SARS-CoV-2
random forest classification
commensal organisms
Prevotella
url https://www.frontiersin.org/articles/10.3389/fmicb.2022.1009440/full
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