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@article{Li:2021:10.1016/S2666-5247(21)00145-2,
author = {Li, HK and Kaforou, M and Rodriguez-Manzano, J and Channon-Wells, S and Monir, A and Habgood-Coote, D and Gupta, RK and Mills, EA and Lin, J and Chiu, Y-H and Pennisi, I and Miglietta, L and Mehta, R and Obaray, N and Herberg, JA and Wright, VJ and Georgiou, P and Shallcross, LJ and Mentzer, AJ and Levin, M and Cooke, GS and Noursadeghi, M and Sriskandan, S},
doi = {10.1016/S2666-5247(21)00145-2},
journal = {The Lancet Microbe},
pages = {594--603},
title = {Discovery and validation of a 3-gene signature to distinguish COVID-19 and other viral infections in emergency infectious disease presentations; a case-control then observational cohort study},
url = {http://dx.doi.org/10.1016/S2666-5247(21)00145-2},
volume = {2},
year = {2021}
}

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TY  - JOUR
AB  - 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 sought to derive and validate a blood transcriptional signature to detect viral infections including COVID-19 among adults with suspected infection presenting to the Emergency Department (ED).Methods: Blood RNA sequencing was performed on a discovery cohort of adults attending the ED with suspected infection who had subsequently-confirmed viral, bacterial, or no infection diagnoses. Differentially expressed host genes were subjected to feature selection to derive the most parsimonious discriminating signature. RT-qPCR validation of the signature was then performed in a prospective cohort of ED patients presenting with undifferentiated fever, and a second case-control cohort of ED patients with COVID-19 or bacterial infection. Signature performance was assessed by calculating area under receiver-operating characteristic curves (AUC-ROCs), sensitivities, and specificities.Findings: A 3-gene transcript signature was derived from the discovery cohort of 56 bacterial and 27 viral infection cases. In the validation cohort of 200 cases, the signature differentiated bacterial from viral infections with an AUC-ROC of 0.976 (95% CI: 0.919-1.000), sensitivity 97.3% and specificity of 100%. The AUC-ROC for C-reactive protein (CRP) and leucocyte count (WCC) was 0.833 (95% CI: 0.694-0.944) and 0.938 (95% CI: 0.840-0.986) respectively. The signature achieved higher net benefit in decision curve analysis than either CRP or WCC for discriminating viral infections from all other cases. In the second validation analysis the signature discriminated 35 bacterial infections from 34 SARS-CoV-2 positive COVID-19 infections with AUC-ROC of 0.953 (95% CI: 0.893-0.992), sensitivity 88.6% and specificity of 94.1%.Interpretation: This novel 3-gene signature discriminates viral i
AU  - Li,HK
AU  - Kaforou,M
AU  - Rodriguez-Manzano,J
AU  - Channon-Wells,S
AU  - Monir,A
AU  - Habgood-Coote,D
AU  - Gupta,RK
AU  - Mills,EA
AU  - Lin,J
AU  - Chiu,Y-H
AU  - Pennisi,I
AU  - Miglietta,L
AU  - Mehta,R
AU  - Obaray,N
AU  - Herberg,JA
AU  - Wright,VJ
AU  - Georgiou,P
AU  - Shallcross,LJ
AU  - Mentzer,AJ
AU  - Levin,M
AU  - Cooke,GS
AU  - Noursadeghi,M
AU  - Sriskandan,S
DO  - 10.1016/S2666-5247(21)00145-2
EP  - 603
PY  - 2021///
SN  - 2666-5247
SP  - 594
TI  - Discovery and validation of a 3-gene signature to distinguish COVID-19 and other viral infections in emergency infectious disease presentations; a case-control then observational cohort study
T2  - The Lancet Microbe
UR  - http://dx.doi.org/10.1016/S2666-5247(21)00145-2
UR  - https://doi.org/10.1016/S2666-5247(21)00145-2
UR  - http://hdl.handle.net/10044/1/89138
VL  - 2
ER  -

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