The COVID-19 has been spreading all over the world, and human health is at stake. Conventional medicine played an important role in the treatment and syndrome relief, while there is limited research evidence to support any prevention or antiviral treatment for COVID-19. Yupingfengsan is a classic formula with the effect of replenishing qi, consolidating exterior, and arresting sweating. Yupingfengsan has been widely used to treat various diseases in China and Southeast Asia for hundreds of years. Accumulating evidence suggests that YPFS has both immune-regulatory and anti-virus effects clinically, but leaving the mechanism elusive. In this paper, we reviewed the recent progress of Yupingfengsan in immune-regulatory and anti-virus activities, including the effect on mucosal immunity, biological antagonism, macrophages, adaptive immunity, and natural killer cells. From this systematic review, we speculate that YPFS can play an effective role in the prevention of SARS-CoV-2, but further experimental studies are expected to investigate the specific mechanisms. This review suggests an alternative direction for the prevention of COVID-19. Received: 12 July 2024 | Revised: 18 September 2024 | Accepted: 21 October 2024 Conflicts of Interest The authors declare that they have no conflicts of interest to this work. Data Availability Statement Data sharing is not applicable to this article as no new data were created or analyzed in this study. Author Contribution Statement Xin Yang: Methodology, Formal analysis, Investigation, Resources, Writing - original draft, Visualization. Rong Tian: Conceptualization, Methodology, Formal analysis, Investigation, Writing - original draft, Writing - review & editing, Supervision, Funding acquisition. Catherine Shi: Conceptualization, Methodology, Formal analysis, Investigation, Writing - original draft, Writing - review & editing. Alan Wang: Conceptualization, Methodology, Formal analysis, Investigation, Resources, Writing - original draft, Writing - review & editing, Supervision.
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