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Distinct inflammatory biomarkers associated with rheumatological outcomes in chronic chikungunya disease

Year: 2026

Type: article

Abstract: Chikungunya virus (CHIKV) poses an enduring public health threat in endemic regions and can progress from acute febrile illness to chronic, disabling rheumatologic disease. We performed an unmatched case-control study of 20 patients sampled during the acute phase (< 14 days) and 20 recruited ≥ 90 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-α and IL-1RA, whereas CCD displayed a broader, non-resolving profile enriched for IL-21, GM-CSF, IL-23, LT-α, 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.

Source: Scientific Reports

DOI: 10.1038/s41598-026-35570-x