Natural and genetically-modified animal models to investigate pulmonary and extrapulmonary manifestations of COVID-19.

Coronavirus disease-19 (COVID-19), a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is a primarily respiratory tract disease. Suitable animal models for COVID-19 are required to study various aspects of pathogenesis, drug discovery, effective and safe vaccine development. Several laboratory animals including, non-human primates, hamsters, ferrets, transgenic mice, and zebrafish, have been used and proven their significance experimentally. Currently available animal models of SARS-CoV-2 can be broadly classified into two categories 1) natural animal models 2) genetically-modified that exhibit different degrees of susceptibility of SARS-CoV-2, tissue damage in respiratory and other organ systems. Not all the available animal models mimic COVID-19-like phenotype completely. Therefore, understanding various aspects of COVID-19 requires different animal models. In this review article, we provide an update on the immune response and clinical manifestations observed in naturally occurring and genetically-modified animals of COVID-19. We then review the transmission, viral replication, lung pathology, immunological aspects, and extrapulmonary phenotypes observed in various animal models. In the end, we put forth our perspective on the anticipated uses, disadvantages, and limitations of each type of animal model.