Table 2.

Animal models of influenza virus and SARS-CoV-2 infection and pathogenesis

Animal	Physiology and genetics	Influenza virus	SARS-CoV-2
Mouse	Popular model for acute lung injury Key differences from humans in anatomy and respiratory cell distribution Differences in physiological responses (no fever or sneezing or coughing) Not a model for transmission Many genetic tools: knockouts, reporters and other transgenics	Diverse viral strains that recapitulate spectrum of human disease, including acute respiratory distress syndrome Mouse adaptation not required for some IAVs, including avian viruses Many immunological tools to study host response	Mice require introduction of human ACE2 receptor (transgenic animal or viral transduction) for infection with unadapted virus Mouse-adapted SARS-CoV-2 does cause severe disease Together, diverse mouse models can recapitulate spectrum of disease in humans
Hamster	Small animal model of contact and airborne transmission for some viruses Limited genetic tools, but some genetic knockouts for key immune genes available	IAVs typically infect without adaptation Primarily upper respiratory tract infection with limited pathology Model for contact transmission and some evidence of airborne transmission Limited immunological tools to study host response	Unadapted SARS-CoV-2 infects hamsters Infection causes mild to moderate pathology in respiratory tract Some evidence that the model can recapitulate age- and sex-based differences in disease severity witnessed in humans Model for contact transmission and some evidence of airborne transmission
Ferret	Respiratory anatomy similar to humans Many respiratory viruses do not require adaptation for infection/pathogenesis Similarities in physiological responses (fever and sneezing) Model for transmission Outbred animals Few genetic tools	IAVs typically infect without adaptation (human and avian IAVs) Reporter viruses available to trace spread (fluorescent and luciferase-based) Limited immunological tools to study host response, but many are in development	Limited studies on SARS-CoV-2 transmission and pathogenesis thus far Unadapted SARS-CoV-2 infects ferrets Current models do not recapitulate severe disease in humans
Non-human primate	Respiratory anatomy most similar to humans Respiratory viruses do not require adaptation for infection or pathogenesis Similarities in physiological response (fever and respiratory distress) Outbred animals Few genetic tools Often serve as gatekeepers of vaccine candidates and therapeutics	IAVs infect without adaptation (human and avian viruses) Frequently used to study highly pathogenic IAVs Limited immunological tools to study host response	SARS-CoV-2 infects NHPs without adaptation of virus or manipulation of host Current models do not recapitulate severe disease in humans Clinical symptoms allow for testing efficacy of therapeutics NHPs exhibit adaptive immune responses to vaccination and infection

ACE2, angiotensin-converting enzyme 2; IAV, influenza A virus; NHP, non-human primate; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.