Temporal Dynamics of the Immune Response in Severe Cases of Human Kyasanur Forest Disease Virus (KFDV) Infection

The immunopathogenesis of KFDV is not well understood. The study's primary objective was to investigate the magnitude and dynamics of cytokine and cellular immune responses during the acute and convalescent phases of KFDV infection in humans. Additionally, the study aimed to identify potential biomarkers that could indicate severe KFD and help predict disease prognosis. In this study, KFDV-positive patients were prospectively enrolled, and peripheral blood samples were collected and analyzed for cellular and cytokine levels, along with the clinical and virological characteristics. Our findings revealed distinctive cytokine profiles differentiating severe from mild KFD during the acute phase of illness. Serum levels of IFN-γ, IP-10, MCP-1, HGF, and IL-2R were markedly elevated in severe KFD. Also, the frequency of activated B cells (CD20lowCD71high) and expression of exhaustion markers (PD-1, CTLA-4) on CD8⁺ T cells was significantly increased in severe cases. The study also describes the persistence of elevated cytokines during the convalescent phase, indicating that prolonged inflammation may be due to dysregulated immune response characterized by sustained T cell activation, cytotoxic activity (Granzyme B, Perforin), and elevated exhaustion markers (PD-1, CTLA-4), particularly in patients with severe KFD. This novel work has important implications for KFDV vaccine research and may aid clinical decision-making in treating severe KFDV infections in humans.