{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T20:24:16Z","timestamp":1783110256012,"version":"3.54.6"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (\n                      <jats:italic>IFI27<\/jats:italic>\n                      ) in COVID-19 patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We show that\n                      <jats:italic>IFI27<\/jats:italic>\n                      is expressed in the respiratory tract of COVID-19 patients and elevated\n                      <jats:italic>IFI27<\/jats:italic>\n                      expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood\n                      <jats:italic>IFI27<\/jats:italic>\n                      expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure),\n                      <jats:italic>IFI27<\/jats:italic>\n                      expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore,\n                      <jats:italic>IFI27<\/jats:italic>\n                      is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1\/09 influenza virus infection,\n                      <jats:italic>IFI27-<\/jats:italic>\n                      like genes were highly upregulated in the blood samples of severely infected patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These data suggest that prognostic biomarkers targeting the family of\n                      <jats:italic>IFI27<\/jats:italic>\n                      genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2022.1060438","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T13:20:34Z","timestamp":1672924834000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":63,"title":["IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study"],"prefix":"10.3389","volume":"13","author":[{"given":"Maryam","family":"Shojaei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Shamshirian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Monkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Grice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin Wee","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siok Min","family":"Teo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Rodrigues Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"McCulloch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Nalos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maedeh","family":"Raei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Razavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roya","family":"Ghasemian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mobina","family":"Gheibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Roozbeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Sly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten M.","family":"Spann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keng Yih","family":"Chew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanshan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra Cristina","family":"Senegaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen L\u00facia","family":"Kuniyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio Luciano","family":"Franck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Flavia Ribeiro","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia de","family":"Noronha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Motamen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Valadan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omolbanin","family":"Amjadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajan","family":"Gogna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esha","family":"Madan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Alizadeh-Navaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Lamperti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Zu\u00f1iga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefania","family":"Nova-Lamperti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Labarca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Knippenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Velma","family":"Herwanto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Phu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Chew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Kwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Teoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiana M.","family":"Pelaia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Win Sen","family":"Kuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette","family":"Jee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Iredell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"O\u2019Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Fraser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle T.","family":"Belz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid E.","family":"Warkiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Salomon","family":"Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Souza-Fonseca-Guimaraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Mclean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arutha","family":"Kulasinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty R.","family":"Short","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/rmv.2146","article-title":"Predictors of COVID-19 severity: A literature review","volume":"31","author":"Gallo Marin","year":"2021","journal-title":"Rev Med Virol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12559-020-09812-7","article-title":"An early warning tool for predicting mortality risk of COVID-19 patients using machine learning","author":"Chowdhury","year":"2021","journal-title":"Cogn Comput"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1016\/j.immuni.2020.10.008","article-title":"Plasma proteomics identify biomarkers and pathogenesis of COVID-19","volume":"53","author":"Shu","year":"2020","journal-title":"Immunity"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02098-2016","article-title":"A novel immune biomarker IFI27 discriminates between influenza and bacteria in patients with suspected respiratory infection","volume":"49","author":"Tang","year":"2017","journal-title":"Eur Respir J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1046\/j.0014-2956.2001.02545.x","article-title":"The interferon alpha induced protein ISG12 is localized to the nuclear membrane","volume":"268","author":"Martensen","year":"2001","journal-title":"Eur J Biochem"},{"key":"B6","doi-asserted-by":"publisher","first-page":"198149","DOI":"10.1016\/j.virusres.2020.198149","article-title":"IFI27 as a potential indicator for severe enterovirus 71-infected hand foot and mouth disease","volume":"289","author":"Min","year":"2020","journal-title":"Virus Res"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s41065-020-00167-5","article-title":"IFI27 may predict and evaluate the severity of respiratory syncytial virus infection in preterm infants","volume":"158","author":"Gao","year":"2021","journal-title":"Hereditas"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1101\/2020.11.04.20225557","article-title":"Spatial profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures","author":"Kulasinghe","year":"2020","journal-title":"medRxiv"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1101\/2020.05.18.20105171","article-title":"Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2","author":"Mick","year":"2020","journal-title":"medRxiv"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2374","DOI":"10.3390\/cells9112374","article-title":"Single-cell transcriptome analysis highlights a role for neutrophils and inflammatory macrophages in the pathogenesis of severe COVID-19","volume":"9","author":"Shaath","year":"2020","journal-title":"Cells"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1101\/2020.03.15.20033472","article-title":"Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19","author":"Huang","year":"2020","journal-title":"MedRxiv"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202201458","article-title":"ScRNA-seq expression of IFI27 and APOC2 identifies four alveolar macrophage superclusters in healthy BALF","volume":"5","author":"Li","year":"2022","journal-title":"Life Sci Alliance"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1101\/gr.276175.121","article-title":"Plasma cell-free RNA characteristics in COVID-19 patients","author":"Wang","year":"2022","journal-title":"Genome Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1101\/2021.01.18.21250044","article-title":"Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV 2 infection","author":"Gupta","year":"2021","journal-title":"medRxiv"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201241","article-title":"Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling","volume":"217","author":"Israelow","year":"2020","journal-title":"J Exp Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.cels.2020.10.003","article-title":"Large-Scale multi-omic analysis of COVID-19 severity","volume":"12","author":"Overmyer","year":"2021","journal-title":"Cell Syst"},{"key":"B17","unstructured":""},{"key":"B18","article-title":"Basic principles of ROC analysis","volume":"4","author":"Metz","year":"1978","journal-title":"Seminars in nuclear medicine"},{"key":"B19","volume-title":"A dictionary of statistics 3e: Oxford university press","author":"Upton","year":"2014"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12920-020-0672-7","article-title":"Pathway mapping of leukocyte transcriptome in influenza patients reveals distinct pathogenic mechanisms associated with progression to severe infection","volume":"13","author":"Zerbib","year":"2020","journal-title":"BMC Med Genomics"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.911873","article-title":"A robust experimental and computational analysis framework at multiple resolutions, modalities and coverages","volume":"13","author":"Tran","year":"2022","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"100242","DOI":"10.1016\/j.xcrm.2021.100242","article-title":"Spatial mapping of SARS-CoV-2 and H1N1 lung injury identifies differential transcriptional signatures","volume":"2","author":"Margaroli","year":"2021","journal-title":"Cell Rep Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03148-w","article-title":"Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia","volume":"590","author":"Grant","year":"2021","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1101\/2021.03.08.434300","article-title":"Pediatric nasal epithelial cells are less permissive to SARS-CoV-2 replication compared to adult cells","author":"Zhu","year":"2021","journal-title":"bioRxiv"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1016\/j.cell.2020.04.026","article-title":"Imbalanced host response to SARS-CoV-2 drives development of COVID-19","volume":"181","author":"Blanco-Melo","year":"2020","journal-title":"Cell"},{"key":"B27","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.immuni.2021.01.017","article-title":"Leveraging the antiviral type I interferon system as a first line of defense against SARS-CoV-2 pathogenicity","volume":"54","author":"Hoagland","year":"2021","journal-title":"Immunity"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd4585","article-title":"Autoantibodies against type I IFNs in patients with life-threatening COVID-19","volume":"370","author":"Bastard","year":"2020","journal-title":"Science"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd4570","article-title":"Inborn errors of type I IFN immunity in patients with life-threatening COVID-19","volume":"370","author":"Zhang","year":"2020","journal-title":"Science"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2588-y","article-title":"Longitudinal analyses reveal immunological misfiring in severe COVID-19","volume":"584","author":"Lucas","year":"2020","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41392-021-00526-2","article-title":"Dynamic blood single-cell immune responses in patients with COVID-19","volume":"6","author":"Huang","year":"2021","journal-title":"Signal transduction targeted Ther"},{"key":"B32","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.trsl.2021.07.006","article-title":"Cluster of highly expressed interferon-stimulated genes associate more with African ancestry than disease activity in patients with systemic lupus erythematosus. A systematic review of cross-sectional studies","volume":"238","author":"Siddiqi","year":"2021","journal-title":"Transl Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1060438\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T13:20:38Z","timestamp":1672924838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1060438\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,5]]},"references-count":32,"alternative-id":["10.3389\/fimmu.2022.1060438"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1060438","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.10.29.21265555","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,5]]},"article-number":"1060438"}}