Aspectos imunológicos, clínicos e viral associados à imunopatogênese da artralgia persistente após infecção pelo vírus Chikungunya

Abstract

INTRODUCTION: Since its re-emergence in 2013, the chikungunya virus (CHIKV) has caused numerous outbreaks worldwide, particularly affecting Latin America and Brazil. The most common symptoms among infected individuals include fever, severe arthralgia, joint swelling, myalgia, and headache. Arthralgia may persist for months or even years after symptom onset, and although some risk factors have been described, the mechanisms and immunopathogenesis underlying persistent arthralgia following CHIKV infection remain unknown. OBJECTIVE: To investigate clinical risk factors, immunological and viral biomarkers associated with the development of chronic arthralgia following CHIKV infection during the disease course. MATERIALS AND METHODS: This study evaluated 71 patients with confirmed chikungunya diagnosis by RT-qPCR, monitored in a cohort to collect information on the chronicity of arthralgia or symptom resolution and to obtain biological samples. Clinical and sociodemographic characteristics were assessed at visits conducted 0-7 and 10-45 days after symptom onset (DPS), respectively. For a subgroup (n=25), at least one additional follow-up with sample collection was conducted beyond 45 days after symptom onset. In these samples, anti-CHIKV IgM and IgG antibodies, the levels of 19 cytokines, chemokines, and growth factors were analyzed, as well as CHIKV viral load and full genome sequencing. RESULTS: Most of the patients studied were female, accounting for 67% (48/71) of the total, with a median age of 40 years. Among them, 59% (42/71) developed chronic arthralgia (>90 days after symptom onset). These individuals exhibited a higher frequency of edema and were, on average, older during the initial phase of the disease (0-7 DPS) compared to the group that did not develop chronic arthralgia. Paired samples showed seroconversion of IgM and IgG antibodies in 96% (70/71) and 100% (71/71) of patients, respectively. Approximately 30% of those who developed chronic arthralgia maintained detectable IgM antibody levels for more than two years after symptom onset. Furthermore, elevated levels of GM-CSF and IP-10/CXCL10 were observed in samples collected between 0-7 and 10-45 DPS, respectively, in the group that developed chronic arthralgia. On the other hand, viral load was not associated with the development of chronic arthralgia, and the mutations found in viral genomes had no clinically significant impact. CONCLUSIONS: The presence of edema and older age were identified in this study as factors associated with the development of chronic arthralgia. The use of opioids during the early phase of the disease was more common in patients who progressed to chronic arthralgia, suggesting more severe symptoms and the need for specific pain management strategies. Intrinsic characteristics of the individual and immune response appear to play a more important role than viral factors in the progression to chronic arthralgia.