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10.1016/S2666-5247(21)00145-2 http://scihub22266oqcxt.onion/10.1016/S2666-5247(21)00145-2 34423323!8367196!34423323     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=34423323&cmd=llinks): Failed to open stream: HTTP request failed! 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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 |pdf=|usr=}}{{34423323}} gab.com Text 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 JO: Lancet Microbe http://www.kidney.de/pget.php?&tw=1&pmid=34423323 #FOAvip 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 HERC6, IGF1R, and NAGK, was derived from the discovery cohort of 56 participants with bacterial infections and 27 with viral infections. In the validation cohort of 200 participants, the signature differentiated bacterial from viral infections with an AUROC of 0.976 (95% CI 0.919-1.000), sensitivity of 97.3% (85.8-99.9), and specificity of 100% (63.1-100). The AUROC for C-reactive protein (CRP) was 0.833 (0.694-0.944) and for leukocyte count was 0.938 (0.840-0.986). The signature achieved higher net benefit in decision curve analysis than either CRP or leukocyte count for discriminating viral infections from all other infections. In the second validation analysis, which included SARS-CoV-2-positive participants, the signature discriminated 35 bacterial infections from 34 SARS-CoV-2-positive COVID-19 infections with AUROC of 0.953 (0.893-0.992), sensitivity 88.6%, and specificity of 94.1%. 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. Twit Text FOAVip 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 ????Lancet Microbe http://www.kidney.de/pget.php?&tw=1&pmid=34423323 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34423323 #FOAvip English Wikipedia <ref>{{Cite pmid|34423323}}</ref> 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 #MMPMID34423323 Li HK; Kaforou M; Rodriguez-Manzano J; Channon-Wells S; Moniri A; Habgood-Coote D; Gupta RK; Mills EA; Arancon D; Lin J; Chiu YH; Pennisi I; Miglietta L; Mehta R; Obaray N; Herberg JA; Wright VJ; Georgiou P; Shallcross LJ; Mentzer AJ; Levin M; Cooke GS; Noursadeghi M; Sriskandan S Lancet Microbe 2021[Nov]; 2 (11): e594-e603 PMID34423323show ga 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 HERC6, IGF1R, and NAGK, was derived from the discovery cohort of 56 participants with bacterial infections and 27 with viral infections. In the validation cohort of 200 participants, the signature differentiated bacterial from viral infections with an AUROC of 0.976 (95% CI 0.919-1.000), sensitivity of 97.3% (85.8-99.9), and specificity of 100% (63.1-100). The AUROC for C-reactive protein (CRP) was 0.833 (0.694-0.944) and for leukocyte count was 0.938 (0.840-0.986). The signature achieved higher net benefit in decision curve analysis than either CRP or leukocyte count for discriminating viral infections from all other infections. In the second validation analysis, which included SARS-CoV-2-positive participants, the signature discriminated 35 bacterial infections from 34 SARS-CoV-2-positive COVID-19 infections with AUROC of 0.953 (0.893-0.992), sensitivity 88.6%, and specificity of 94.1%. 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. |*Bacterial Infections/diagnosis[MESH] |*COVID-19/diagnosis[MESH] |*Communicable Diseases[MESH] |*Virus Diseases/diagnosis[MESH] |Adolescent[MESH] |Adult[MESH] |Bacteria[MESH] |C-Reactive Protein/analysis[MESH] |Case-Control Studies[MESH] |Cohort Studies[MESH] |Humans[MESH]Discovery and validation of a three-gene signature to distinguish COVI(epmc).pdf DeepDyve Pubget Overpricing