Abstract
The immunopathogenesis of chikungunya virus (CHIKV) infection and the role of acute-phase immune response on joint pain persistence is not fully understood. We investigated the profile of serum chemokine and cytokine in CHIKV-infected patients with acute disease, compared the levels of these biomarkers to those of patients with other acute febrile diseases (OAFD) and healthy controls (HC), and evaluated their role as predictors of chronic arthralgia development. Chemokines and cytokines were measured by flow Cytometric Bead Array. Patients with CHIKV infection were further categorized according to duration of arthralgia (≤ 3 months vs >3 months), presence of anti-CHIKV IgM at acute-phase sample, and number of days of symptoms at sample collection (1 vs 2-3 vs ≥4). Patients with acute CHIKV infection had significantly higher levels of CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-1β, IL-6, IL-12, and IL-10 as compared to HC. CCL2, CCL5, and CXCL10 levels were also significantly higher in patients with CHIKV infection compared to patients with OAFD. Patients whose arthralgia lasted > 3 months had increased CXCL8 levels compared to patients whose arthralgia did not (p<0.05). Multivariable analyses further indicated that high levels of CXCL8 and female sex were associated with arthralgia lasting >3 months. Patients with chikungunya and OAFD had similar cytokine kinetics for IL-1β, IL-12, TNF, IFN-γ, IL-2, and IL-4, although the levels were lower for CHIKV patients. This study suggests that chemokines may have an important role in the immunopathogenesis of chronic chikungunya-related arthralgia.
Highlights
In the last decade, chikungunya virus (CHIKV) has caused several outbreaks worldwide and became a serious public health issue in the South and Central Americas, mainly in Brazil [1, 2]
Patients with other acute febrile diseases (OAFD) had longer duration of symptoms when presenting for initial care (median: 3 days; interquartile range (IQR): 2-4) compared to patients with chikungunya (P
We found that chikungunya patients who developed chronic arthralgia had higher levels of CXCL8 in the acute phase of the disease compared to those who did not, even after adjusting for age, sex and number of days of symptoms at the time of sample collection
Summary
Chikungunya virus (CHIKV) has caused several outbreaks worldwide and became a serious public health issue in the South and Central Americas, mainly in Brazil [1, 2]. The first autochthonous cases of CHIKV infection in Brazil were reported in September 2014, in the city of Oiapoque, and in the city of Feira de Santana, States of Amapá and Bahia, respectively [3,4,5]. Acute CHIKV infection in humans may cause mild to moderate febrile disease, which is typically accompanied by rash, headache, myalgia, and intense polyarthralgia. Chronic arthralgia post-CHIKV infection can lead to limitation of movements, incapacity for work, and even depression, directly affecting household incomes and representing a significant disease burden for affected populations [8,9,10]. It is necessary to elucidate the mechanisms that lead to chronic articular pain in some patients with chikungunya in order to prevent this complication
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