Animal models for COVID-19: advances, gaps and perspectives

Area of Science:

• Virology
• Immunology
• Comparative Medicine

Background:

• Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) causes COVID-19, a global pandemic necessitating robust research tools.
• Animal models are vital for understanding SARS-CoV-2 pathogenesis, host immune responses, and developing vaccines and therapeutics.
• Existing animal models for COVID-19 have limitations in evaluating variants of concern, antibody-dependent enhancement, and comorbidities.

Purpose of the Study:

• To review the clinical features of COVID-19 across different populations.
• To summarize the characteristics of current major animal models for SARS-CoV-2 infection.
• To propose improvements for future animal models, particularly genetically modified mice.

Main Methods:

• Review of clinical manifestations of COVID-19 in humans.
• Analysis of naturally susceptible animal models (non-human primates, hamsters, ferrets, minks, poultry, livestock).
• Evaluation of modified mouse models (genetically modified, AAV/adenoviral transduced, human tissue engraftment) and receptor/protease studies.

Main Results:

• Various animal models exhibit different susceptibilities and responses to SARS-CoV-2.
• Genetically modified mice and those engrafted with human tissues show promise but require refinement.
• Understanding host ACE2 receptor and protease interactions is key to model development.

Conclusions:

• Current animal models have deficits for fully evaluating SARS-CoV-2 virulence, ADE, and comorbidities.
• Further development of genetically modified mouse models, focusing on receptor genes and genetic engineering techniques, is essential.
• Novel animal models are urgently needed to advance COVID-19 research and counter emerging variants.