Longitudinal immune signatures in influenza A patients administered Lianhua Qingwen capsules.

BACKGROUND: LHQW, a traditional Chinese medicine formulation, had been reported to accelerate symptom recovery in patients with influenza A virus (IAV) infection, yet the underlying immunological mechanisms remained largely unexplored. METHODS: We integrated 41-plex CyTOF, RNA-seq, and Olink to characterize longitudinal peripheral immune signatures in IAV-infected patients receiving LHQW, and validated key findings using in vitro functional assays with active components and an in vivo IAV mouse model. RESULTS: IAV infection induced broad perturbations across innate and adaptive immunity. LHQW treatment was associated with functional tuning across immune compartments, including enhanced monocyte activation with increased CD25 and CD40, and augmented CD8+ T-cell activation accompanied by attenuation of inhibitory checkpoints including PD-1 and CD39 across multiple CD8+ T-cell subsets. Intercorrelation analyses further suggested a temporal shift from a partially activated yet inhibition-leaning state on day 3 toward a more coordinated pattern of myeloid-lymphoid activation by day 7. Consistent with these clinical immune signatures, salidroside, an active component of LHQW, increased the frequency of CD40+ non-classical monocytes, whereas kaempferol reduced the frequencies of PD-1+ and CD39+ cells within CD8+ T cells in vitro. In a mouse model of IAV infection, high‑dose LHQW recapitulated key aspects of this immunomodulatory pattern and reduced pulmonary viral RNA loads. CONCLUSIONS: These findings revealed time-dependent peripheral immune remodeling associated with LHQW treatment during recovery from IAV infection.