Animal Models for the Study of SARS-CoV-2–Induced Respiratory Disease and Pathology

Abstract

Emergence of the betacoronavirus SARS-CoV-2 has resulted in a historic pandemic, with millions of deaths worldwide. An unprecedented effort has been made by the medical, scientific, and public health communities to rapidly develop and implement vaccines and therapeutics to prevent and reduce hospitalizations and deaths. Although SARS-CoV-2 infection can lead to disease in many organ systems, the respiratory system is its main target, with pneumonia and acute respiratory distress syndrome as the hallmark features of severe disease. The large number of patients who have contracted COVID-19 infections since 2019 has permitted a detailed characterization of the clinical and pathologic features of the disease in humans. However, continued progress in the development of effective preventatives and therapies requires a deeper understanding of the pathogenesis of infection. Studies using animal models are necessary to complement in vitro findings and human clinical data. Multiple animal species have been evaluated as potential models for studying the respiratory disease caused by SARS-CoV-2 infection. Knowing the similarities and differences between animal and human responses to infection is critical for effective translation of animal data into human medicine. This review provides a detailed summary of the respiratory disease and associated pathology induced by SARS-CoV-2 infection in humans and compares them with the disease that develops in 3 commonly used models: NHP, hamsters, and mice. The effective use of animals to study SARS-CoV-2–induced respiratory disease will enhance our understanding of SARS-CoV-2 pathogenesis, allow the development of novel preventatives and therapeutics, and aid in the preparation for the next emerging virus with pandemic potential.

Characterization of a SARS-CoV-2 Omicron BA.5 direct-contact transmission model in hamsters

“…To study intervention strategies against SARS-CoV-2 and its variants, well-characterized animal models are indispensable. Multiple species, including non-human primates, ferrets, hamsters, and (transgenic) mice have been used [9][10][11][12] . Whereas the susceptibility of mice to SARS-CoV-2 is variable, and depends on the genetic background and viral variant, ferrets and hamsters are naturally susceptible to most variants 13,14 .…”

Establishment and characterization of an hACE2/hTMPRSS2 knock-in mouse model to study SARS-CoV-2

“…Animal models have been extensively used to study pathogenesis of acute SARS-CoV-2 infection and for evaluating COVID-19 countermeasures including vaccines and therapeutics (reviewed in ( 9 )). Syrian hamsters typically recover from weight loss and interstitial pneumonia after SARS-CoV-2 infection, but are not widely used because of their size, aggressiveness, cost to maintain, and unfamiliar biology and husbandry requirements ( 9 – 12 ). Mice are especially valuable as COVID-19 models due to their rapid breeding, gestation, growth rates, highly characterized immune systems, and ease of genetic manipulation.…”