{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:48:40Z","timestamp":1791946120916,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Respiratory viral infections (RVIs) are a major cause of global morbidity and mortality. Severe cases are driven by dysregulated inflammation, impaired interferon (IFN) responses, and thromboinflammation, yet the mechanisms underlying endothelial dysfunction remain poorly defined. We collected 234 leftover material samples from hospitalized patients with PCR\u2010confirmed RVIs. Patients were stratified by viral etiology, differential involvement of the respiratory tract, age and possible co\u2010infections. Cytokines (IL\u20106, IL\u20108, IL\u20101\u03b2, TNF\u2010\u03b1), IFNs (\u03b1\/\u03b2\/\u03b3), and endothelial markers (ICAM\u20101, VCAM\u20101) were quantified using microfluidic immunoassays. Routine coagulation parameters were measured in a subset of patients. Compared with controls, RVI patients exhibited significantly elevated systemic cytokines (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). IL\u20106 and IL\u20108 were higher in patients with lower respiratory tract involvement, particularly in influenza cases. Elderly patients displayed reduced IFN\u2010\u03b1\/\u03b2 responses but increased proinflammatory CRP levels. Infants and children had higher ICAM\u20101 but lower CRP levels. Patients with viral\u2013bacterial co\u2010infections showed amplified IFN\u2010\u03b3\/IL\u20101\u03b2\/ICAM\u20101 response. Older adults demonstrated prolonged prothrombin times and reduced fibrinogen, indicating coagulopathy. Severe RVIs are characterized by a triad of impaired antiviral IFN responses, hyperinflammation, and endothelial activation, culminating in thromboinflammation. Age, viral type and co\u2010infections critically shape host responses, underscoring the need for biomarker\u2010guided, personalized therapies.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70784","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T08:39:41Z","timestamp":1767170381000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cytokine and Endothelial Activation Patterns Related to Severe and Non\u2010Severe Respiratory Viral Infections"],"prefix":"10.1002","volume":"98","author":[{"given":"Roberto","family":"Ferrarese","sequence":"first","affiliation":[{"name":"Department of Medicine and Technological Innovation University of Insubria Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Boutahar","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences University of Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo Paolo","family":"Genoni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological Innovation University of Insubria Varese Italy"},{"name":"Ospedale di Circolo e Fondazione Macchi Laboratory of Medical Microbiology and Virology Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Arcari","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological Innovation University of Insubria Varese Italy"},{"name":"Ospedale di Circolo e Fondazione Macchi Laboratory of Medical Microbiology and Virology Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Zambon","sequence":"additional","affiliation":[{"name":"Ospedale di Circolo e Fondazione Macchi Laboratory of Medical Microbiology and Virology Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1868-1444","authenticated-orcid":false,"given":"Maria","family":"Dolci","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences University of Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Perego","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences University of Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"D'alessandro","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences University of Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Delbue","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences University of Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicasio","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological Innovation University of Insubria Varese Italy"},{"name":"Ospedale di Circolo e Fondazione Macchi Laboratory of Medical Microbiology and Virology Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Signorini","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences University of Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2741-8840","authenticated-orcid":false,"given":"Federica","family":"Novazzi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological Innovation University of Insubria Varese Italy"},{"name":"Ospedale di Circolo e Fondazione Macchi Laboratory of Medical Microbiology and Virology Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0051-2022"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-021-05996-x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","unstructured":"T. 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