{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T01:34:55Z","timestamp":1769564095712,"version":"3.49.0"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sanyo Chemical Industries, Ltd."},{"name":"Fujirebio, Inc."},{"name":"Mizuho Medy, Co., Ltd."},{"name":"VisGene, Co., Ltd."},{"name":"Canon medical systems Co."},{"name":"CarbGeM Inc."},{"name":"SB Coronavirus Inspection Center Corp."},{"name":"Canon medical systems Co."},{"name":"Ezaki Glico Co., Ltd."},{"name":"SB Coronavirus Inspection Center Corp."},{"name":"Nippon genetics Co., Ltd."}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Although biomarkers to predict coronavirus disease 2019 (COVID-19) severity have been studied since the early pandemic, no clear guidelines on using them in clinical practice are available. Here, we examined the ability of four biomarkers to predict disease severity using conserved sera from COVID-19 patients who received inpatient care between January 1, 2020 and September 21, 2021 at the National Center for Global Health and Medicine, collected at the appropriate time for prediction. We predicted illness severity in two situations: 1) prediction of future oxygen administration for patients without oxygen support within 8 days of onset (Study 1) and 2) prediction of future mechanical ventilation support (excluding non-invasive positive pressure ventilation) or death of patients within 4 days of the start of oxygen administration (Study 2). Interleukin-6, IFN-\u03bb3, thymus and activation-regulated chemokine, and calprotectin were measured retrospectively. Other laboratory and clinical information were collected from medical records. AUCs were calculated from ROC curves and compared for the predictive ability of the four biomarkers. Study 1 included 18 patients, five of whom had developed oxygen needs. Study 2 included 45 patients, 13 of whom required ventilator management or died. In Study 1, IFN-\u03bb3 showed a good predictive ability with an AUC of 0.92 (95% CI 0.76\u20131.00). In Study 2, the AUC of each biomarker was 0.70\u20130.74. The number of biomarkers above the cutoff showed the possibility of good prediction with an AUC of 0.86 (95% CI 0.75\u20130.97). When two or more biomarkers were positive, sensitivity and specificity were 0.92 and 0.63, respectively. In terms of biomarker testing at times when prognostication may be clinically useful, IFN-\u03bb3 was predictive of oxygenation demand and a combination of the four biomarkers was predictive of mechanical ventilator requirement.<\/jats:p>","DOI":"10.1371\/journal.pone.0279897","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T17:51:26Z","timestamp":1680198686000},"page":"e0279897","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Validation of the severe COVID-19 prognostic value of serum IL-6, IFN-\u03bb3, CCL17, and calprotectin considering the timing of clinical need for prediction"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6218-523X","authenticated-orcid":true,"given":"Kei","family":"Yamamoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Ohsiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3165-9062","authenticated-orcid":true,"given":"Tetsuya","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiyo","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Miura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maki","family":"Nagashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriko","family":"Iwamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko S.","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2202-5527","authenticated-orcid":true,"given":"Moto","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wataru","family":"Sugiura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Nebuya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Kurokawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Ohmagari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"issue":"3","key":"pone.0279897.ref001","doi-asserted-by":"crossref","first-page":"174","DOI":"10.35772\/ghm.2020.01054","article-title":"COVID-19 can suddenly become severe: a case series from Tokyo, Japan.","volume":"2","author":"K Nakamura","year":"2020","journal-title":"Glob Health Med."},{"key":"pone.0279897.ref002","article-title":"Association between IL-6 and severe disease and mortality in COVID-19 disease: a systematic review and meta-analysis.","author":"X Liu","year":"2021","journal-title":"Postgrad Med J."},{"key":"pone.0279897.ref003","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.ijid.2020.10.003","article-title":"A score combining early detection of cytokines accurately predicts COVID-19 severity and intensive care unit transfer","volume":"101","author":"C Nagant","year":"2020","journal-title":"Int J Infect Dis"},{"key":"pone.0279897.ref004","doi-asserted-by":"crossref","first-page":"155428","DOI":"10.1016\/j.cyto.2021.155428","article-title":"Interleukin-6, procalcitonin and neutrophil-to-lymphocyte ratio: Potential immune-inflammatory parameters to identify severe and fatal forms of COVID-19","volume":"141","author":"W Sayah","year":"2021","journal-title":"Cytokine"},{"issue":"1","key":"pone.0279897.ref005","doi-asserted-by":"crossref","first-page":"e23657","DOI":"10.1002\/jcla.23657","article-title":"Peripheral blood inflammatory markers in predicting prognosis in patients with COVID-19. 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