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We performed an unmatched case\u2013control study of 20 patients sampled during the acute phase (&lt;\u200914 days) and 20 recruited\u2009\u2265\u200990 days after onset who met criteria for chronic chikungunya disease (CCD). At enrolment we quantified 45 serum cytokines\/chemokines by multiplex assay; clinical data were recorded for all, and chronic cases were re-evaluated at 3, 12 and 24 months. CCD participants were older, reported greater initial pain and more often received symptomatic corticosteroids. Acute CHIKV infection showed a focused antiviral signature characterized by higher CCL2, CXCL10, IFN-\u03b1 and IL-1RA, whereas CCD displayed a broader, non-resolving profile enriched for IL-21, GM-CSF, IL-23, LT-\u03b1, IL-4, IL-9, IL-31 and FGF-2. Over follow-up, many CCD cases improved; however, in time-to-discharge analyses, higher IL-23, baseline rheumatoid arthritis, and higher VAS were associated with persistence, whereas higher FGF-2 and IL-4, arthrosis, and anti-CHIKV IgG were associated with earlier resolution. Acute and chronic chikungunya exhibit distinct soluble-mediator signatures. A targeted early antiviral response aligns with recovery, while a broad Th2\/Th17-skewed milieu aligns with chronicity. IL-23, for risk, and FGF-2\/IL-4, for resolution, emerge as candidate biomarkers for risk stratification and therapeutic trials, alongside clinical factors.<\/jats:p>","DOI":"10.1038\/s41598-026-35570-x","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T10:37:36Z","timestamp":1776422256000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Distinct inflammatory biomarkers associated with rheumatological outcomes in chronic chikungunya disease"],"prefix":"10.1038","volume":"16","author":[{"given":"Lucas Sousa","family":"Magalh\u00e3es","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Cardoso","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina Adalva","family":"de Lucena Couto \u00d3cea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Debbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila","family":"Lima dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Mahalingam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro Martins","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia Maria Ribeiro","family":"de Jesus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela Maria","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roque Pacheco","family":"de Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla Nat\u00e1lia Oliveira","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"35570_CR1","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.actatropica.2016.11.020","volume":"166","author":"SV Mayer","year":"2017","unstructured":"Mayer, S. V., Tesh, R. B. & Vasilakis, N. The emergence of arthropod-borne viral diseases: A global prospective on dengue, Chikungunya and Zika fevers. Acta Trop. 166, 115\u2013163 (2017).","journal-title":"Acta Trop."},{"key":"35570_CR2","doi-asserted-by":"publisher","unstructured":"Schwartz, O. & Albert, M. L. Biology and pathogenesis of chikungunya virus. Nature Rev. Microbio.8 491\u2013500 Preprint at (2010). https:\/\/doi.org\/10.1038\/nrmicro2368","DOI":"10.1038\/nrmicro2368"},{"key":"35570_CR3","doi-asserted-by":"crossref","unstructured":"Cavalcante, A. F. L. et al. Chronic Chikungunya arthralgia reduces functionality, quality of life and occupational performance: Descriptive cross-sectional study. BRAZILIAN J. PAIN 5, (2022).","DOI":"10.5935\/2595-0118.20220047-pt"},{"key":"35570_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00739-9","author":"T Cerqueira-Silva","year":"2024","unstructured":"Cerqueira-Silva, T. et al. Risk of death following Chikungunya virus disease in the 100 million Brazilian Cohort, 2015\u201318: A matched cohort study and self-controlled case series. Lancet Infect. Dis. https:\/\/doi.org\/10.1016\/S1473-3099(23)00739-9 (2024).","journal-title":"Lancet Infect. Dis."},{"key":"35570_CR5","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1007\/s42399-023-01386-3","volume":"5","author":"PNG de Almeida","year":"2023","unstructured":"de Almeida, P. N. G. et al. Detection of Chikungunya virus RNA in cerebrospinal fluid of patients with severe neurological disorders. SN Compr. Clin. Med. 5, 50 (2023).","journal-title":"SN Compr. Clin. Med."},{"key":"35570_CR6","doi-asserted-by":"publisher","unstructured":"Amaral, J. K. et al. Pathogenesis of chronic chikungunya arthritis: Resemblances and links with rheumatoid arthritis. 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