{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:18:26Z","timestamp":1787026706852,"version":"build-2736575974"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Elucidation of immune response differences is critical for uncovering underlying mechanisms and developing potential intervention measures among adults and children with COVID-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective study, we analyzed serum biochemical markers and cytokine profiles among adults and children with COVID-19 in the First People\u2019s Hospital of Chenzhou in Hunan, China from 1 December 2022 to 13 February 2023. A case\u2013control study was conducted using propensity score matching (PSM) to mitigate possible confounding factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The significant differences observed included lymphocyte exhaustion, an increased neutrophil-to-lymphocyte (NEU\/LYM) ratio, high levels of C-reactive protein (CRP), and a cytokine storm, characterized by high levels of Th1 proinflammatory cytokines, including interleukin 1\u03b2 (IL-1\u03b2), IL-6, IL-8, interferon type I (IFN-\n                      <jats:italic>\u03b3<\/jats:italic>\n                      ), and tumor necrosis factor (TNF-\n                      <jats:italic>\u03b1<\/jats:italic>\n                      ) in the lung among severe adult COVID-19 patients. Additionally, systemic immune responses were observed in children with COVID-19.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Significant differences in immune responses between adults and children with COVID-19 highlight the different mechanisms and potential intervention measures of COVID-19.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1525051","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T01:34:57Z","timestamp":1738632897000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Age-related immune response disparities between adults and children with severe COVID-19: a case\u2013control study in China"],"prefix":"10.3389","volume":"16","author":[{"given":"Hongliang","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingkai","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yefei","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinglan","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixing","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.3389\/fmicb.2016.01841","article-title":"Immune responses to influenza virus and its correlation to age and inherited factors","volume":"7","author":"Bahadoran","year":"2016","journal-title":"Front. 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Rev."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.3390\/microorganisms11041048","article-title":"Special issue: advances in SARS-CoV-2 infection","volume":"11","author":"Contini","year":"2023","journal-title":"Microorganisms"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"157","DOI":"10.23750\/abm.v91i1.9397","article-title":"WHO declares COVID-19 a pandemic","volume":"91","author":"Cucinotta","year":"2020","journal-title":"Acta Bio-Med. Atenei Parm."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"156287","DOI":"10.1016\/j.cyto.2023.156287","article-title":"Emerging aspects of cytokine storm in COVID-19: the role of proinflammatory cytokines and therapeutic prospects","volume":"169","author":"Dharra","year":"2023","journal-title":"Cytokine"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e20200702","DOI":"10.1542\/peds.2020-0702","article-title":"Epidemiology of COVID-19 among children in China","volume":"145","author":"Dong","year":"2020","journal-title":"Pediatrics"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1002\/jmv.20268","article-title":"A comparison of epidemiologic and immunologic features of bronchiolitis caused by influenza virus and respiratory syncytial virus","volume":"75","author":"Garofalo","year":"2005","journal-title":"J. Med. 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Biol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1126\/science.abc6027","article-title":"Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients","volume":"369","author":"Hadjadj","year":"2020","journal-title":"Science"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e0130324","DOI":"10.1128\/mbio.01303-24","article-title":"SARS-CoV-2 infection induces hyaluronan production in vitro and hyaluronan levels in COVID-19 patients relate to morbidity and long-term lung impairment: a prospective cohort study","volume":"15","author":"Hellman","year":"2024","journal-title":"MBio"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"566","DOI":"10.3389\/fimmu.2019.00566","article-title":"Role of type I interferon (IFN) in the respiratory syncytial virus (RSV) immune response and disease severity","volume":"10","author":"Hijano","year":"2019","journal-title":"Front. 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Virol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"147612","DOI":"10.1016\/j.gene.2023.147612","article-title":"Targeting cytokine storm as the potential anti-viral therapy: implications in regulating SARS-CoV-2 pathogenicity","volume":"881","author":"Maity","year":"2023","journal-title":"Gene"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1002\/jmv.27405","article-title":"Role of toll-like receptors in modulation of cytokine storm signaling in SARS-CoV-2-induced COVID-19","volume":"94","author":"Manik","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1214\/aoms\/1177730491","article-title":"On a test of whether one of two random variables is stochastically larger than the other","volume":"18","author":"Mann","year":"1947","journal-title":"Ann. Math. 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Immunol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"4632","DOI":"10.1016\/j.cell.2023.08.044","article-title":"Multi-omics analysis of mucosal and systemic immunity to SARS-CoV-2 after birth","volume":"186","author":"Wimmers","year":"2023","journal-title":"Cell"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1080\/22221751.2020.1747363","article-title":"Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients","volume":"9","author":"Xiong","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/s41590-023-01724-6","article-title":"Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2","volume":"25","author":"Yin","year":"2024","journal-title":"Nat. Immunol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1007\/s11596-021-2318-1","article-title":"Differences in immune responses between children and adults with COVID-19","volume":"41","author":"Yuan","year":"2021","journal-title":"Curr Med. 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