Topological data analysis, including persistent homology, has undergone significant development in recent years. However, one outstanding challenge is to build a coherent statistical inference procedure on persistent diagrams. The paired dependent data structure, as birth and death in persistent diagrams, adds additional complexity to the development. In this paper, we present a new lattice path representation for persistent diagrams. A new exact statistical inference procedure is developed for lattice paths via combinatorial enumerations. The proposed lattice path method is applied to the topological characterization of the protein structures of COVID-19 viruse. We demonstrate that there are topological changes during the conformation change of spike proteins that are needed to initiate the infection of host cells.