Table 1. Common animal models for COVID-19 immunobiology research.

Animal	Immunopathology	Immune response	Advantage	Disadvantages
NHPs	Diffuse alveolar damage Lung consolidation Infiltration of inflammatory cells Thoracic adhesion Glassy opacity Hepatosplenopathy Age-related pathological changes	Neutralizing antibody response Virus-specific T cell response Up-regulation of IL-1, IL-6, IL-10, and other inflammatory factors Transient neutropenia and lymphocytopenia	Closer to human immune response Essential models for preclinical trials	Lack of severe clinical symptoms High technical requirements for biosecurity High experimental costs
hACE2 transgenic mice	Severe interstitial pneumonia Infiltration of inflammatory cells Thickening of alveolar septum Unique vascular system damage	Lymphopenia Pulmonary immune cell recruitment Up-regulation of IFN-γ, IL-6, MCP-1 and other inflammatory factors Diffuse microglia activation	Excellent simulation of severe COVID-19 Dose-dependent respiratory symptoms and mortality Central nervous system infection	Vastly different ACE2 expression pattern from humans Complex and expensive transgenic operations Lack of genetic diversity and disease models
AdV/AAV-hACE2 mice	Infiltration of inflammatory cells from perivascular to mesenchymal Diffuse alveolar intraepithelial infection Alveolar edema Increased vascular congestion and bleeding	Virus-specific T cell response Up-regulation of TNF-α, IFN-γ, IL-10 and other inflammatory factors Reduced activation of CD4+, CD8+, or NK cells	Fast and simple model construction Diverse genetic backgrounds or disease models Suitable for large-scale drug and vaccine research	Interference from anti-Adv/AAV immune response Time and tissue limitations of viral infection
Mouse adapted SARS-COV-2	Interstitial pneumonia Edema Diffuse alveolar damage Mild to moderate lung inflammation	Proinflammatory and monocyte chemokine responses Up-regulation of IL-6, IL-1α, IL-1β and other inflammatory factors	Easy to simulate multiple COVID-19 symptoms Diverse genetic backgrounds or disease models	Clinical SARS-CoV-2 strains cannot be used
Syrian hamsters	Alveolar destruction Monocyte infiltration Alveolar collapse Lung consolidation Pulmonary hemorrhage	Neutralizing antibody response Infiltration of macrophages and T lymphocytes Up-regulation of IFN-γ, IL-4, IL-6 and other inflammatory factors	Naturally susceptible to SARS-CoV-2 Similar to human COVID-19 symptoms Suitable for large-scale drug and vaccine research	Lack of reagents and tools for immunology research Lack of genetic diversity and disease models