{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T20:23:26Z","timestamp":1789071806861,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470007"],"award-info":[{"award-number":["82470007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82530002"],"award-info":[{"award-number":["82530002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2300501"],"award-info":[{"award-number":["2021YFC2300501"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Influenza Resp Viruses"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>COVID\u201019 has caused over 7 million deaths worldwide and remains a critical public health threat. The marked heterogeneity in immune responses among patients poses challenges for targeted treatment. Molecular classification is essential for guiding precision therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed unsupervised consensus clustering on blood transcriptomic data from 351 COVID\u201019 patients to identify molecular endotypes and validated the classification in an independent cohort of 56 patients. To identify robust endotype\u2010specific biomarkers, we applied XGBoost, LASSO, and random forest algorithms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Three endotypes with distinct biological and clinical profiles were identified. Endotype 1, associated with favorable outcomes, showed enriched DNA replication pathways and elevated IL7 expression. Endotype 2 featured hypoxia and angiotensin\u2010related pathways. Endotype 3 exhibited TLR4 activation, IL\u20101\u03b2 upregulation, and impaired NK cytotoxicity, correlating with poor outcomes. All endotypes shared type I interferon activation. Predictive biomarker pairs included STAT4:S100A11 (endotype 1), SLC4A1:RPL31 (endotype 2), and RALB:MTR (endotype 3), enabling endotype classification with high accuracy. Importantly, these biomarker genes can be reliably measured in peripheral blood using RT\u2010qPCR, making the classification model feasible for clinical application.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This molecular classification reveals heterogeneity in COVID\u201019 and proposes biomarker\u2010guided strategies for patient stratification and management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/irv.70227","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T08:11:06Z","timestamp":1770711066000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Classification of Patients With COVID\u201019 Based on Transcriptional Profiling"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1624-8681","authenticated-orcid":false,"given":"Hongyu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, China\u2013Japan Friendship Hospital Capital Medical University  Beijing People's Republic of China"},{"name":"National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Department of Pulmonary and Critical Care Medicine, New Cornerstone Science Foundation, Center of Respiratory Medicine, China\u2010Japan Friendship Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, China\u2013Japan Friendship Hospital Capital Medical University  Beijing People's Republic of China"},{"name":"National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Department of Pulmonary and Critical Care Medicine, New Cornerstone Science Foundation, Center of Respiratory Medicine, China\u2010Japan Friendship Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Deng","sequence":"additional","affiliation":[{"name":"Tsinghua University\u2010Peking University Joint Center for Life Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxue","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, China\u2013Japan Friendship Hospital  Beijing People's Republic of China"},{"name":"Institute of Respiratory Medicine Chinese Academy of Medical Sciences  Beijing People's Republic of China"},{"name":"Peking University China\u2013Japan Friendship School of Clinical Medicine  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, China\u2013Japan Friendship Hospital Capital Medical University  Beijing People's Republic of China"},{"name":"National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Department of Pulmonary and Critical Care Medicine, New Cornerstone Science Foundation, Center of Respiratory Medicine, China\u2010Japan Friendship Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Zuo","sequence":"additional","affiliation":[{"name":"National Center for Respiratory Medicine  Beijing People's Republic of China"},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity  Beijing People's Republic of China"},{"name":"National Clinical Research Center for Respiratory Diseases  Beijing People's Republic of China"},{"name":"Department of Pulmonary and Critical Care Medicine Center of Respiratory Medicine, China\u2013Japan Friendship Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitian","family":"Xu","sequence":"additional","affiliation":[{"name":"National Center for Respiratory Medicine  Beijing People's Republic of China"},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity  Beijing People's Republic of China"},{"name":"National Clinical Research Center for Respiratory Diseases  Beijing People's Republic of China"},{"name":"Department of Pulmonary and Critical Care Medicine Center of Respiratory Medicine, China\u2013Japan Friendship Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhui","family":"Shen","sequence":"additional","affiliation":[{"name":"National Center for Respiratory Medicine  Beijing People's Republic of China"},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity  Beijing People's Republic of China"},{"name":"National Clinical Research Center for Respiratory Diseases  Beijing People's Republic of China"},{"name":"Department of Pulmonary and Critical Care Medicine Center of Respiratory Medicine, China\u2013Japan Friendship Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Li","sequence":"additional","affiliation":[{"name":"National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Department of Pulmonary and Critical Care Medicine, New Cornerstone Science Foundation, Center of Respiratory Medicine, China\u2010Japan Friendship Hospital  Beijing People's Republic of China"},{"name":"Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, China\u2013Japan Friendship Hospital  Beijing People's Republic of China"},{"name":"Institute of Respiratory Medicine Chinese Academy of Medical Sciences  Beijing People's Republic of China"},{"name":"Peking University China\u2013Japan Friendship School of Clinical Medicine  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, China\u2013Japan Friendship Hospital Capital Medical University  Beijing People's Republic of China"},{"name":"National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Department of Pulmonary and Critical Care Medicine, New Cornerstone Science Foundation, Center of Respiratory Medicine, China\u2010Japan Friendship Hospital  Beijing People's Republic of China"},{"name":"Tsinghua University\u2010Peking University Joint Center for Life Sciences  Beijing People's Republic of China"},{"name":"Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, China\u2013Japan Friendship Hospital  Beijing People's Republic of China"},{"name":"Institute of Respiratory Medicine Chinese Academy of Medical Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25158155"},{"key":"e_1_2_10_3_1","unstructured":"WHO.World Health Organization Coronavirus Disease (COVID\u201019) Situation Reports https:\/\/www.who.int\/emergencies\/diseases\/novel\u2010coronavirus\u20102019\/situation\u2010reports(2024)."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm8108"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102711"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201021289\u2010y"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj7521"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010020\u201000823\u20105"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1167917"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.04.017"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.002"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc6027"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(20)30628\u20100"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102567"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2020.04.002"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbae124"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab568"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1152223"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00592\u20102022"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107615"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.013"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3967"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts034"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq170"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0377\u20100427(87)90125\u20107"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010014\u20100550\u20108"},{"key":"e_1_2_10_27_1","unstructured":"T.ChenandC.GuestrininProceedings of the 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining.785\u2013794."},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1996.tb02080.x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010933404324"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20102600(17)30294\u20101"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20107493\u20101_12"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v061.i06"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.12839"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28728"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1043219"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.29497"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10142\u2010024\u201001359\u20102"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.07.026"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10983"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.12.020"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3174"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2022.156049"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2010.09.002"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.24172"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40560\u2010020\u201000453\u20104"}],"container-title":["Influenza and Other Respiratory Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/irv.70227","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/irv.70227","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/irv.70227","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:18:34Z","timestamp":1773026314000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/irv.70227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/irv.70227"],"URL":"https:\/\/doi.org\/10.1111\/irv.70227","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/IRV.70227\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/IRV.70227\/v1\/decision1","asserted-by":"object"}]},"ISSN":["1750-2640","1750-2659"],"issn-type":[{"value":"1750-2640","type":"print"},{"value":"1750-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70227"}}