Abstract
Several animal models have been developed to study the pathophysiology of SARS-CoV-2 infection and to evaluate vaccines and therapeutic agents for this emerging disease. Similar to infection with SARS-CoV-1, infection of Syrian hamsters with SARS-CoV-2 results in moderate respiratory disease involving the airways and lung parenchyma but does not lead to increased mortality. Using a combination of immunohistochemistry and transmission electron microscopy, we showed that the epithelium of the conducting airways of hamsters was the primary target for viral infection within the first 5 days of infection, with little evidence of productive infection of pneumocytes. At 6 days postinfection, antigen was cleared but parenchymal damage persisted, and the major pathological changes resolved by day 14. These findings are similar to those previously reported for hamsters with SARS-CoV-1 infection. In contrast, infection of K18-hACE2 transgenic mice resulted in pneumocyte damage, with viral particles and replication complexes in both type I and type II pneumocytes together with the presence of convoluted or cubic membranes; however, there was no evidence of virus replication in the conducting airways. The Syrian hamster is a useful model for the study of SARS-CoV-2 transmission and vaccination strategies, whereas infection of the K18-hCE2 transgenic mouse results in lethal disease with fatal neuroinvasion but with sparing of conducting airways.
Highlights
Several animal models have been developed to study the pathophysiology of SARS-CoV-2 infection and to evaluate vaccines and therapeutic agents for this emerging disease
Since the emergence of a novel coronavirus (SARS-CoV-2) in China with rapid spread around the world, there has been a concentrated effort to understand the pathophysiology of COVID-19, and to compare it with the lesions caused by other coronaviruses such as SARS-CoV-1 and MERS-CoV
The initial postmortem studies on human patients with fatal COVID-19 appeared to show a histological picture similar to that seen with SARS-CoV-1 infection; in retrospect, this may have represented a publication bias because, similar to the 2003 outbreak, there were few studies done on tissues from the conducting airways or from patients in the early stages of disease
Summary
Several animal models have been developed to study the pathophysiology of SARS-CoV-2 infection and to evaluate vaccines and therapeutic agents for this emerging disease. At 6 days postinfection, antigen was cleared but parenchymal damage persisted, and the major pathological changes resolved by day 14 These findings are similar to those previously reported for hamsters with SARS-CoV-1 infection. Cells, endothelial cells, and exudate in the first 2 phases, but not in the third.[30] There has been conflicting data on virus presence by ultrastructure.[47] As the 2 most common laboratory animals for study of SARS-CoV-2 pathology have been the Syrian hamster and the B6.Cg-Tg(K18-ACE2)2Prlmn/J transgenic mouse, the objective of this study was to determine which cells in the respiratory tract are infected with SARS-CoV-2, to characterize the relative benefits and drawbacks of these animal models
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