Discovery and validation of a three-gene signature to distinguish COVID-19 and other viral infections in emergency infectious disease presentations: a case-control and observational cohort study.
Journal
The Lancet. Microbe
ISSN: 2666-5247
Titre abrégé: Lancet Microbe
Pays: England
ID NLM: 101769019
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
pubmed:
24
8
2021
medline:
24
8
2021
entrez:
23
8
2021
Statut:
ppublish
Résumé
Emergency admissions for infection often lack initial diagnostic certainty. COVID-19 has highlighted a need for novel diagnostic approaches to indicate likelihood of viral infection in a pandemic setting. We aimed to derive and validate a blood transcriptional signature to detect viral infections, including COVID-19, among adults with suspected infection who presented to the emergency department. Individuals (aged ≥18 years) presenting with suspected infection to an emergency department at a major teaching hospital in the UK were prospectively recruited as part of the Bioresource in Adult Infectious Diseases (BioAID) discovery cohort. Whole-blood RNA sequencing was done on samples from participants with subsequently confirmed viral, bacterial, or no infection diagnoses. Differentially expressed host genes that met additional filtering criteria were subjected to feature selection to derive the most parsimonious discriminating signature. We validated the signature via RT-qPCR in a prospective validation cohort of participants who presented to an emergency department with undifferentiated fever, and a second case-control validation cohort of emergency department participants with PCR-positive COVID-19 or bacterial infection. We assessed signature performance by calculating the area under receiver operating characteristic curves (AUROCs), sensitivities, and specificities. A three-gene transcript signature, comprising This novel three-gene signature discriminates viral infections, including COVID-19, from other emergency infection presentations in adults, outperforming both leukocyte count and CRP, thus potentially providing substantial clinical utility in managing acute presentations with infection. National Institute for Health Research, Medical Research Council, Wellcome Trust, and EU-FP7.
Sections du résumé
BACKGROUND
Emergency admissions for infection often lack initial diagnostic certainty. COVID-19 has highlighted a need for novel diagnostic approaches to indicate likelihood of viral infection in a pandemic setting. We aimed to derive and validate a blood transcriptional signature to detect viral infections, including COVID-19, among adults with suspected infection who presented to the emergency department.
METHODS
Individuals (aged ≥18 years) presenting with suspected infection to an emergency department at a major teaching hospital in the UK were prospectively recruited as part of the Bioresource in Adult Infectious Diseases (BioAID) discovery cohort. Whole-blood RNA sequencing was done on samples from participants with subsequently confirmed viral, bacterial, or no infection diagnoses. Differentially expressed host genes that met additional filtering criteria were subjected to feature selection to derive the most parsimonious discriminating signature. We validated the signature via RT-qPCR in a prospective validation cohort of participants who presented to an emergency department with undifferentiated fever, and a second case-control validation cohort of emergency department participants with PCR-positive COVID-19 or bacterial infection. We assessed signature performance by calculating the area under receiver operating characteristic curves (AUROCs), sensitivities, and specificities.
FINDINGS
A three-gene transcript signature, comprising
INTERPRETATION
This novel three-gene signature discriminates viral infections, including COVID-19, from other emergency infection presentations in adults, outperforming both leukocyte count and CRP, thus potentially providing substantial clinical utility in managing acute presentations with infection.
FUNDING
National Institute for Health Research, Medical Research Council, Wellcome Trust, and EU-FP7.
Identifiants
pubmed: 34423323
doi: 10.1016/S2666-5247(21)00145-2
pii: S2666-5247(21)00145-2
pmc: PMC8367196
doi:
Substances chimiques
C-Reactive Protein
9007-41-4
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
e594-e603Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203141/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R502376/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206508/Z/17/Z
Pays : United Kingdom
Informations de copyright
© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
Déclaration de conflit d'intérêts
We declare no competing interests.
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