Estudo prospectivo do perfil de citocinas em mulheres com diagnóstico confirmado de Chikungunya nas fases aguda, pós-aguda e crônica acompanhadas em uma Unidade Básica de Saúde em Fortaleza, Ceará

Abstract

Chikungunya (CHIK) is an acute febrile arthritic disease transmitted through the bite of Aedes aegypti and Aedes albopictus mosquitoes. Three phases of this disease are described: acute, post-acute, and chronic. Approximately 50% of patients affected by CHIK may develop polyarthralgia and/or chronic polyarthritis. Despite the widespread distribution of CHIK cases worldwide, there is still no specific antiviral treatment available or validated biomarkers for prognosis. The pathophysiology of CHIK has not yet been fully elucidated. Therefore, this study analyzed the cytokine profile of female patients with a confirmed diagnosis of CHIK, across the three phases of the disease, treated at a Basic Health Unit in Fortaleza, Ceará. Furthermore, we investigated whether there is an association between cytokine levels and persistent arthralgias and whether there is a correlation between cytokine concentrations and the presence of comorbidities in the patients evaluated. This prospective cohort study, conducted between 2021 and 2024, included 40 female patients and 10 controls (healthy women). In addition to collecting blood samples for cytokine levels (GM-CSF, INF-gamma, IL-1 B, IL-2, IL-4, IL-6, IL-10, IL-17A, IL-18, MCP-1) at five time points (days 0, 21, 90, 120, 180, and 360 after initial symptoms), clinical and epidemiological data were obtained through questionnaires. Cytokine profile analysis was performed using Milliplex assays. Student's t-test, Mann-Whitney test, chi-square test, Fisher's exact test, and Friedman test were used. Values of p < 0.05 were considered statistically significant. The analyses were performed using R software. The mean age of the study participants was 47.3 years. Persistent pain was reported by more than half of the patients (57.9%), while comorbidities were present in 45% of cases. Among these, the most frequent were diabetes mellitus and systemic arterial hypertension. Finally, the evaluation of longitudinal variations in cytokine levels in patients with CHIK revealed significant differences over time for IL-10 and IL-18. IL-10 levels showed a sustained increase from D21 onwards, with significant differences between D0 and D180 and between D0 and D360 (p = 0.027). IL-18, in turn, showed a significant increase between D0 and D21 (p = 0.020). The dynamic behavior of cytokines throughout the phases of CHIK can be explained by several factors, such as host immunogenetics. Therefore, further studies on the kinetics of cytokines in CHIK are necessary, targeting, for example, IL-10 and IL-18, to understand the pathophysiology of the disease in more detail and, thus, in the future, use cytokines as therapeutic targets and biomarkers of disease chronicity and severity.