Cytokine profiling in oropouche fever highlights dissociation between systemic immunity and viral load.

Oropouche virus (OROV), a member of the Peribunyaviridae family, is an emerging arthropod-borne virus that has recently expanded across Brazilian states, establishing new transmission hotspots beyond the Amazon Basin. OROV infection causes an acute febrile illness with symptoms similar to those of other arboviruses. However, recent reports of fatal cases and vertical transmission leading to congenital anomalies have highlighted OROV as an emerging public health concern. In this study, we conducted an in-depth analysis of cytokine networks during acute Oropouche fever in patients with confirmed OROV infection. Using commercial cytokine panels, we quantified circulating inflammatory cytokines and chemokines and evaluated their correlations with viral load (inferred from cycle threshold values). OROV-infected patients exhibited a distinctive cytokine profile, with significant elevations in pro-inflammatory mediators including IL-18, monocyte chemoattractant protein-1, and tendency to increase IFN-α2, whereas IL-33 and TNF-α were reduced compared with healthy controls. Network analysis revealed tightly interconnected cytokines interactions during disease progression. Notably, inflammatory mediator levels did not correlate with viral load, indicating that systemic cytokine responses operate independently of viral replication kinetics. These findings reveal a unique inflammatory signature in OROV infection, suggesting specific pathogenic mechanisms important for understanding disease progression and developing therapeutic strategies.