{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T16:28:44Z","timestamp":1786638524051,"version":"build-2736575974"},"reference-count":73,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n The role of chemokine C-C motif ligand 5 (CCL5) in respiratory viral infections remains controversial; although essential for viral clearance, it is also implicated in pathogenic hyperinflammation.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To quantify associations between CCL5 levels and unfavorable disease progression and mortality in respiratory viral infections.<\/jats:p>\n <\/jats:sec>\n \n Data Sources<\/jats:title>\n Medline and PubMed, Embase, Scopus, Web of Science, the Cochrane Library, CABI Digital Library, and Global Health (Ovid) were searched from inception to October 1, 2025.<\/jats:p>\n <\/jats:sec>\n \n Study Selection<\/jats:title>\n Observational studies evaluating the association of CCL5 levels with clinical severity or survival in patients with confirmed respiratory viral infections.<\/jats:p>\n <\/jats:sec>\n \n Data Extraction and Synthesis<\/jats:title>\n Two reviewers independently extracted data and assessed risk of bias (Newcastle-Ottawa Scale) and certainty of evidence (GRADE). Data were pooled using a random-effects model following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data analysis was performed from September 2025 to December 2025.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Unfavorable disease progression (severity) and all-cause mortality.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The meta-analysis included 18 studies (2376 patients; median age, 58.2 [range, 0.08-65.0] years; 1278 of 2126 male [60.1%]); 12 studies (67%) were of high methodological quality. Eleven studies (1214 patients) evaluated disease progression and 7 (1162 patients) evaluated mortality. Elevated CCL5 levels were associated with reduced odds of unfavorable disease progression (OR, 0.78; 95% CI, 0.71-0.85;\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u20090%) and mortality (OR, 0.65; 95% CI, 0.55-0.76;\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200923.1%). The protective association had significantly larger effect sizes for mortality than for disease progression (\n P<\/jats:italic>\n \u2009=\u2009.047 for interaction). Subgroup analyses for disease progression demonstrated consistent protective associations without significant interaction by virus type (coronavirus: OR, 0.80 [95% CI, 0.70-0.90] vs noncoronavirus: OR, 0.74 [95% CI, 0.63-0.87]) or age group (pediatric: OR, 0.79 [95% CI, 0.69-0.90] vs adult: OR, 0.75 [95% CI, 0.63-0.88]). Results remained consistent in sensitivity analyses.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this systematic review and meta-analysis of 18 observational studies, elevated CCL5 levels were associated with favorable outcomes and survival in respiratory viral infections, reflecting a competent antiviral immune response rather than pathogenic hyperinflammation. These findings suggest that CCL5 may serve as a prognostic biomarker for risk stratification.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.28987","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T15:30:31Z","timestamp":1786635031000},"page":"e2628987","source":"Crossref","is-referenced-by-count":0,"title":["CCL5 Levels, Disease Progression, and Mortality in Respiratory Viral Infections"],"prefix":"10.1001","volume":"9","author":[{"given":"Carlos","family":"Pita-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad. Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Sep\u00falveda-Crespo","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad. 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