Pro-Inflammatory Cytokines as Early Predictors of Chronic Rheumatologic Disease Following Chikungunya Virus Infection.

Background/Objectives: Infection with the Chikungunya virus (CHIKV) results in acute febrile diseases with severe polyarthritis, which can be followed by chronic rheumatic disease and long-term disability. To evaluate cytokine profiles in acute and chronic CHIKV infection and examine the relationship with clinical outcomes, including persistent musculoskeletal symptoms. Methods: Literature search was carried out systematically using electronic databases (PubMed, Embase, Scopus, and Google Scholar). Studies that met eligibility criteria were observational or intervention cohorts that measured levels of cytokines/chemokines in laboratory-confirmed CHIKV patients in acute (<3 months) or chronic (>3 months) phases. Data was extracted on the study design, population, biomarkers, and clinical outcomes. As the assays were not homogeneous in terms of timing, outcome, and definitions, the findings were synthesized in narrative form using tabular representation. Results: A total of 21 studies, including 4216 participants, were incorporated. In acute CHIKV, interleukin-6 (IL-6) (reported to be elevated in 81% of studies), IL-8 (77%), TNF-α (65%), and IFN-γ (60%) were most consistently increased, alongside interferon-inducible chemokines CXCL10/IP-10 and MCP-1. Chronic-phase cohorts showed persistent elevation of IL-6 (69%), IL-8 (63%), TNF-α (58%), and IL-17 (41%), especially among patients with prolonged arthralgia or arthritis. Chronic musculoskeletal symptoms were reported in 25-65% of cases, with some persisting beyond five years. A high degree of heterogeneity was observed in assay procedures and time of sampling. Conclusions: CHIKV infection is characterized by acute inflammatory surges and, in some cases, persistent cytokine dysregulation linked to chronic arthritis. These results showed the importance of prognostic biomarkers and targeted therapy.