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Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Title: Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study
Authors: Gupta, Rishi K; Rosenheim, Joshua; Bell, Lucy C; Chandran, Aneesh; Guerra-Assuncao, Jose A; Pollara, Gabriele; Whelan, Matthew; Artico, Jessica; Joy, George; Kurdi, Hibba; Altmann, Daniel M; Boyton, Rosemary J; Maini, Mala K; McKnight, Aine; Lambourne, Jonathan; Cutino-Moguel, Teresa; Manisty, Charlotte; Treibel, Thomas A; Moon, James C; Chain, Benjamin M; Noursadeghi, Mahdad; Abbass, Hakam; Abiodun, Aderonke; Alfarih, Mashael; Alldis, Zoe; Amin, Oliver E; Andiapen, Mervyn; Augusto, João B; Baca, Georgiana L; Bailey, Sasha NL; Bhuva, Anish N; Boulter, Alex; Bowles, Ruth; Bracken, Olivia V; O'Brien, Ben; Brooks, Tim; Bullock, Natalie; Butler, David K; Captur, Gabriella; Champion, Nicola; Chan, Carmen; Collier, David; Couto de Sousa, Jorge; Couto-Parada, Xose; Davies, Rhodri H; Douglas, Brooke; Di Genova, Cecilia; Dieobi-Anene, Keenan; Diniz, Mariana O; Ellis, Anaya; Feehan, Karen; Finlay, Malcolm; Fontana, Marianna; Forooghi, Nasim; Gaier, Celia; Gibbons, Joseph M; Gilroy, Derek; Hamblin, Matt; Harker, Gabrielle; Hewson, Jacqueline; Hickling, Lauren M; Hingorani, Aroon D; Howes, Lee; Hughes, Alun; Hughes, Gemma; Hughes, Rebecca; Itua, Ivie; Jardim, Victor; Lee, Wing-Yiu Jason; Jensen, Melaniepetra; Jones, Jessica; Jones, Meleri; Kapil, Vikas; Lin, Kai-Min; Louth, Sarah; Mandadapu, Vineela; Manisty,, Charlotte; McKnight, Áine; Menacho, Katia; Mfuko, Celina; Mitchelmore, Oliver; Moon, Christopher; Moon,, James C; Munoz Sandoval, Diana; Murray, Sam M; Otter, Ashley; Pade, Corinna; Palma, Susana; Parker, Ruth; Patel, Kush; Pawarova, Babita; Petersen, Steffen E; Piniera, Brian; Pieper, Franziska P; Pope, Daniel; Prossora, Maria; Rannigan, Lisa; Rapala, Alicja; Reynolds, Catherine J; Richards, Amy; Robathan, Matthew; Sambile, Genine; Schmidt, Nathalie M; Semper, Amanda; Seraphim, Andreas; Simion, Mihaela; Smit, Angelique; Sugimoto, Michelle; Swadling, Leo; Taylor, Stephen; Temperton, Nigel J.; Thomas, Stephen; Thornton, George D; Tucker, Art; Veerapen, Jessry; Vijayakumar, Mohit; Welch, Sophie; Wodehouse, Theresa; Wynne, Lucinda; Zahedi, Dan
Publisher Information: Elsevier
Publication Year: 2021
Collection: University of Kent: KAR - Kent Academic Repository
Subject Terms: QR355 Virology
Description: Background We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.Methods We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew’s Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for “viral infection”, “transcriptome”, “biomarker”, and “blood”. We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive participants) during their first week of PCR ...
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
ISSN: 2666-5247
Relation: https://kar.kent.ac.uk/89150/1/1-s2.0-S2666524721001464-main.pdf; Gupta, Rishi K, Rosenheim, Joshua, Bell, Lucy C, Chandran, Aneesh, Guerra-Assuncao, Jose A, Pollara, Gabriele, Whelan, Matthew, Artico, Jessica, Joy, George, Kurdi, Hibba, and others. Altmann, Daniel M, Boyton, Rosemary J, Maini, Mala K, McKnight, Aine, Lambourne, Jonathan, Cutino-Moguel, Teresa, Manisty, Charlotte, Treibel, Thomas A, Moon, James C, Chain, Benjamin M, Noursadeghi, Mahdad, Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Altmann, Daniel M, Amin, Oliver E, Andiapen, Mervyn, Artico, Jessica, Augusto, João B, Baca, Georgiana L, Bailey, Sasha NL, Bhuva, Anish N, Boulter, Alex, Bowles, Ruth, Boyton, Rosemary J, Bracken, Olivia V, O'Brien, Ben, Brooks, Tim, Bullock, Natalie, Butler, David K, Captur, Gabriella, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Collier, David, Couto de Sousa, Jorge, Couto-Parada, Xose, Cutino-Moguel, Teresa, Davies, Rhodri H, Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O, Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Gaier, Celia, Gibbons, Joseph M, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hewson, Jacqueline, Hickling, Lauren M, Hingorani, Aroon D, Howes, Lee, Hughes, Alun, Hughes, Gemma, Hughes, Rebecca, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Joy, George, Kapil, Vikas, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Louth, Sarah, Maini, Mala K, Mandadapu, Vineela, Manisty,, Charlotte, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mitchelmore, Oliver, Moon, Christopher, Moon,, James C, Munoz Sandoval, Diana, Murray, Sam M, Noursadeghi, Mahdad, Otter, Ashley, Pade, Corinna, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Babita, Petersen, Steffen E, Piniera, Brian, Pieper, Franziska P, Pope, Daniel, Prossora, Maria, Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Sambile, Genine, Schmidt, Nathalie M, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D, Treibel, Thomas A, Tucker, Art, Veerapen, Jessry, Vijayakumar, Mohit, Welch, Sophie, Wodehouse, Theresa, Wynne, Lucinda, and Zahedi, Dan (hide) (2021) Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study. The Lancet Microbe, . ISSN 2666-5247. (doi:10.1016/S2666-5247(21)00146-4 ) (KAR id:89150 )
DOI: 10.1016/S2666-5247%2821%2900146-4
Availability: https://kar.kent.ac.uk/89150/; https://doi.org/10.1016/S2666-5247%2821%2900146-4
Rights: cc_by
Accession Number: edsbas.D3ABA1C7
Database: BASE