{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T06:01:39Z","timestamp":1770357699978,"version":"3.49.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"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><jats:title>Background<\/jats:title><jats:p>Immune response indicators in the early phase of COVID-19, including interferon and neutralizing responses against SARS-CoV-2, which predict hypoxemia remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This prospective observational study recruited patients hospitalized with COVID-19 (before emergence of omicron variant). As the immune indicators, we assessed the serum levels of IFN-I\/III, IL-6, CXCL10 and VEGF, using an ELISA at within 5 days after the onset of symptoms, and serum neutralizing responses using a pseudovirus assay. We also assessed SARS-CoV-2 viral load by qPCR using nasal-swab specimens and serum, to assess the association of indicators and viral distribution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study enrolled 117 patients with COVID-19, of which 28 patients developed hypoxemia. None received vaccine before admission. Serum IFN-I levels (IFN-\u03b1 and IFN-\u03b2), IL-6, CXCL10, LDH and CRP were significantly higher in patients who developed hypoxemia. A significant association with nasopharyngeal viral load was observed only for IFN-I. The serum levels of IFN-\u03b1, IL-6, CXCL10 were significantly associated with the presence of RNAemia. Multivariable analysis showed higher odds ratio of IFN-\u03b1, with cut-off value of 107 pg\/ml, in regard to hypoxemia (Odds ratio [OR]=17.5; 95% confidence interval [CI], 4.7-85; p&amp;lt;0.001), compared to those of IL-6, &amp;gt;17.9 pg\/ml (OR=10.5; 95% CI, 2.9-46; p&amp;lt;0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrated that serum IFN-\u03b1 levels in the early phase of SARS-CoV-2 infection strongly predict hypoxemic respiratory failure in a manner different from that of the other indicators including IL-6 or humoral immune response, and instead sensitively reflect innate immune response against SARS-CoV-2 invasion.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1197436","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T08:09:51Z","timestamp":1693814991000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Predictive values of immune indicators on respiratory failure in the early phase of COVID-19 due to Delta and precedent variants"],"prefix":"10.3389","volume":"14","author":[{"given":"K.","family":"Nagaoka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Kawasuji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Takegoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Murai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Kaneda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Kimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Tani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Niimi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Morinaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0241536","article-title":"Proportion of asymptomatic infection among COVID-19 positive persons and their transmission potential: A systematic review and meta-analysis","volume":"15","author":"Yanes-Lane","year":"2020","journal-title":"PloS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"103673","DOI":"10.1016\/j.ebiom.2021.103673","article-title":"Complex immune deregulation in severe COVID-19: More than a mechanism of pathogenesis","volume":"73","author":"Giamarellos-Bourboulis","year":"2021","journal-title":"EBioMedicine."},{"key":"B4","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1016\/j.chom.2020.04.009","article-title":"Complex immune dysregulation in COVID-19 patients with severe respiratory failure","volume":"27","author":"Giamarellos-Bourboulis","year":"2020","journal-title":"Cell Host Microbe"},{"key":"B5","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s12016-021-08908-8","article-title":"Identification of parameters representative of immune dysfunction in patients with severe and fatal COVID-19 infection: a systematic review and meta-analysis","volume":"64","author":"Qin","year":"2023","journal-title":"Clin Rev Allergy Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2521-4","article-title":"Factors associated with COVID-19-related death using OpenSAFELY","volume":"584","author":"Williamson","year":"2020","journal-title":"Nature."},{"key":"B7","doi-asserted-by":"publisher","first-page":"117788","DOI":"10.1016\/j.lfs.2020.117788","article-title":"The role of biomarkers in diagnosis of COVID-19 - 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