Korean red ginseng mitigates pulmonary injury and enhances antiviral immunity in a low-dose pseudo-type SARS-CoV-2 infection model.

Objective: Material or subjects: K18-hACE2 transgenic mice were used as an experimental model, and three different Korean red ginseng formulations (non-saponin, saponin, and whole Korean red ginseng extract) were administered prior to infection with the virus. Methods: The physiological and immunological effects of the Korean red ginseng formulations were assessed by monitoring lung histopathology and luciferase activity in lung tissue. Flow cytometry was used to analyze the populations of immune cells in both the lungs and spleen, and serum IgM levels were quantified using an enzyme-linked immunosorbent assay. Results: Low-dose PSV infection induced lung injury and immune cell infiltration in the lung. Administration of Korean red ginseng, particularly the saponin fraction, significantly reduced the excessive activation of interstitial macrophages, NK cells, and cytotoxic T cells. Additionally, Korean red ginseng promoted long-term immune memory by increasing the population of memory B cells and cytotoxic T cells in the spleen. In the treatment groups, IgM production was enhanced upon secondary PSV infection. Conclusions: Korean red ginseng modulates immune responses and promotes long-term immunity against low-dose PSV infection. Our data also support the potential of Korean red ginseng as a complementary therapeutic strategy for COVID-19 and an enhancer of vaccine efficacy.