Human mRNA in saliva can correctly identify individuals harboring acute infection

ABSTRACTThe COVID-19 pandemic demonstrated the poor ability of body temperature to reliably identify SARS-CoV-2-infected individuals, an observation that has been made before in the context of other infectious diseases. While acute infection does not always cause fever, it does reliably drive host t...

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Main Authors: Qing Yang, Nicholas R. Meyerson, Camille L. Paige, James H. Morrison, Stephen K. Clark, Will T. Fattor, Carolyn J. Decker, Halley R. Steiner, Elena Lian, Daniel B. Larremore, Rushika Perera, Eric M. Poeschla, Roy Parker, Robin D. Dowell, Sara L. Sawyer
Format: Article
Language:English
Published: American Society for Microbiology 2023-12-01
Series:mBio
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/mbio.01712-23
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author Qing Yang
Nicholas R. Meyerson
Camille L. Paige
James H. Morrison
Stephen K. Clark
Will T. Fattor
Carolyn J. Decker
Halley R. Steiner
Elena Lian
Daniel B. Larremore
Rushika Perera
Eric M. Poeschla
Roy Parker
Robin D. Dowell
Sara L. Sawyer
author_facet Qing Yang
Nicholas R. Meyerson
Camille L. Paige
James H. Morrison
Stephen K. Clark
Will T. Fattor
Carolyn J. Decker
Halley R. Steiner
Elena Lian
Daniel B. Larremore
Rushika Perera
Eric M. Poeschla
Roy Parker
Robin D. Dowell
Sara L. Sawyer
author_sort Qing Yang
collection DOAJ
description ABSTRACTThe COVID-19 pandemic demonstrated the poor ability of body temperature to reliably identify SARS-CoV-2-infected individuals, an observation that has been made before in the context of other infectious diseases. While acute infection does not always cause fever, it does reliably drive host transcriptional responses as the body responds at the site of infection. These transcriptional changes can occur both in cells that are directly harboring replicating pathogens and in cells elsewhere that receive a molecular signal that infection is occurring. Here, we identify a core set of approximately 70 human genes that are together upregulated in cultured human cells infected by a broad array of viral, bacterial, and fungal pathogens. We have named these “core response” genes. In theory, transcripts from these genes could serve as biomarkers of infection in the human body, in a way that is agnostic to the specific pathogen causing infection. As such, we perform human studies to show that these infection-induced human transcripts can be measured in the saliva of people harboring different types of infections. The number of these transcripts in saliva can correctly classify infection status (whether a person harbors an infection) 91% of the time. Furthermore, in the case of SARS-CoV-2 specifically, the number of core response transcripts in saliva correctly identifies infectious individuals even when enrollees, themselves, are asymptomatic and do not know they are infected.IMPORTANCEThere are a variety of clinical and laboratory criteria available to clinicians in controlled healthcare settings to help them identify whether an infectious disease is present. However, in situations such as a new epidemic caused by an unknown infectious agent, in health screening contexts performed within communities and outside of healthcare facilities or in battlefield or potential biowarfare situations, this gets more difficult. Pathogen-agnostic methods for rapid screening and triage of large numbers of people for infection status are needed, in particular methods that might work on an easily accessible biospecimen like saliva. Here, we identify a small, core set of approximately 70 human genes whose transcripts serve as saliva-based biomarkers of infection in the human body, in a way that is agnostic to the specific pathogen causing infection.
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spelling doaj.art-b08f948d7077422f9f70fcb6440dbffc2023-12-22T19:53:44ZengAmerican Society for MicrobiologymBio2150-75112023-12-0114610.1128/mbio.01712-23Human mRNA in saliva can correctly identify individuals harboring acute infectionQing Yang0Nicholas R. Meyerson1Camille L. Paige2James H. Morrison3Stephen K. Clark4Will T. Fattor5Carolyn J. Decker6Halley R. Steiner7Elena Lian8Daniel B. Larremore9Rushika Perera10Eric M. Poeschla11Roy Parker12Robin D. Dowell13Sara L. Sawyer14BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USABioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USABioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USADivision of Infectious Diseases, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USABioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USABioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USADepartment of Biochemistry, University of Colorado Boulder, Boulder, Colorado, USABioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USACenter for Vector-Borne Infectious Diseases and Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USABioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USACenter for Vector-Borne Infectious Diseases and Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USADivision of Infectious Diseases, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USABioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USABioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USABioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USAABSTRACTThe COVID-19 pandemic demonstrated the poor ability of body temperature to reliably identify SARS-CoV-2-infected individuals, an observation that has been made before in the context of other infectious diseases. While acute infection does not always cause fever, it does reliably drive host transcriptional responses as the body responds at the site of infection. These transcriptional changes can occur both in cells that are directly harboring replicating pathogens and in cells elsewhere that receive a molecular signal that infection is occurring. Here, we identify a core set of approximately 70 human genes that are together upregulated in cultured human cells infected by a broad array of viral, bacterial, and fungal pathogens. We have named these “core response” genes. In theory, transcripts from these genes could serve as biomarkers of infection in the human body, in a way that is agnostic to the specific pathogen causing infection. As such, we perform human studies to show that these infection-induced human transcripts can be measured in the saliva of people harboring different types of infections. The number of these transcripts in saliva can correctly classify infection status (whether a person harbors an infection) 91% of the time. Furthermore, in the case of SARS-CoV-2 specifically, the number of core response transcripts in saliva correctly identifies infectious individuals even when enrollees, themselves, are asymptomatic and do not know they are infected.IMPORTANCEThere are a variety of clinical and laboratory criteria available to clinicians in controlled healthcare settings to help them identify whether an infectious disease is present. However, in situations such as a new epidemic caused by an unknown infectious agent, in health screening contexts performed within communities and outside of healthcare facilities or in battlefield or potential biowarfare situations, this gets more difficult. Pathogen-agnostic methods for rapid screening and triage of large numbers of people for infection status are needed, in particular methods that might work on an easily accessible biospecimen like saliva. Here, we identify a small, core set of approximately 70 human genes whose transcripts serve as saliva-based biomarkers of infection in the human body, in a way that is agnostic to the specific pathogen causing infection.https://journals.asm.org/doi/10.1128/mbio.01712-23innate immunitybiomarkersinfectious disease screeningsalivahost gene transcriptstranscriptional response to infection
spellingShingle Qing Yang
Nicholas R. Meyerson
Camille L. Paige
James H. Morrison
Stephen K. Clark
Will T. Fattor
Carolyn J. Decker
Halley R. Steiner
Elena Lian
Daniel B. Larremore
Rushika Perera
Eric M. Poeschla
Roy Parker
Robin D. Dowell
Sara L. Sawyer
Human mRNA in saliva can correctly identify individuals harboring acute infection
mBio
innate immunity
biomarkers
infectious disease screening
saliva
host gene transcripts
transcriptional response to infection
title Human mRNA in saliva can correctly identify individuals harboring acute infection
title_full Human mRNA in saliva can correctly identify individuals harboring acute infection
title_fullStr Human mRNA in saliva can correctly identify individuals harboring acute infection
title_full_unstemmed Human mRNA in saliva can correctly identify individuals harboring acute infection
title_short Human mRNA in saliva can correctly identify individuals harboring acute infection
title_sort human mrna in saliva can correctly identify individuals harboring acute infection
topic innate immunity
biomarkers
infectious disease screening
saliva
host gene transcripts
transcriptional response to infection
url https://journals.asm.org/doi/10.1128/mbio.01712-23
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