The Immunobiology of COVID-19: Mechanistic and Therapeutic Insights from Animal Models

Due to the intricate distribution of the immune system throughout the body, in vitro assessments of coronavirus disease 2019 (COVID-19) immunobiology often lack reproducibility when extrapolated to the whole organism. Consequently, it is imperative to develop animal models for a comprehensive understanding of the pathology and immunology in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This review summarizes the progress of current COVID-19 animal models, including non-human primates (NHPs), mice, and hamsters, in exploring the mechanisms of immunopathology, immune protective and long-term effects of SARS-CoV-2 infection as revealed by these animal models，as well as their applications in immunoprevention and immunotherapy of SARS-CoV-2 infection. We emphasize the differences among these animal models and their different scopes of application since no single model can fully encapsulate all aspects of COVID-19. To address specific challenges in combating COVID-19, it is crucial to carefully select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities. Optimization of animal model libraries and associated research tools is a key factor to solving the global COVID-19 pandemic and serves as a robust reservoir for future emerging infectious diseases.