2026/07/11 by Thiago Cerqueira-Silva, Laise de Moraes, Blenda de Jesus Pereira +17
paper · doi:10.1093/infdis/jiag366
Abstract Background Postacute viral syndromes are increasingly recognized as causes of prolonged disability, with a notably higher prevalence in women. This study investigated the immune signature of individuals who progressed to chronic chikungunya (CC), a condition characterized by persistent arthralgia and examined the role of biological sex in disease outcomes. Methods We analyzed peripheral blood mononuclear cells from patients, recruited between 2016 and 2020, sampled within 7 days of disease onset. The study compared patients who eventually recovered (RC, n = 11) with those who progressed to CC (n = 24), alongside 9 healthy controls. We identified differentially expressed genes using bulk RNA-seq and validated key findings by qRT-PCR and flow cytometry. Results Ten genes were differentially expressed between CC and RC. Specifically, IKZF2 was upregulated in CC patients, which was validated by qRT-PCR. Conversely, ACKR3 was upregulated in RC patients, a finding validated by flow cytometry. Furthermore, CC cases demonstrated higher viral loads and downregulation of IFN-α and IFN-γ pathways compared to RC. We also found that immune profiles differed between men and women; specifically, IFNα and IFN-γ and TNF-signaling pathways were upregulated in women with CC but downregulated in men with CC relative to recovered individuals. Conclusion Our findings suggest that progression to CC is influenced by an impaired early antiviral response combined with sex-specific immune regulation. Furthermore, ACKR3 and IKZF2 were identified as potential prognostic biomarkers for CC. These biomarkers may enable early identification of patients at risk of chronic disease, informing timely intervention strategies.