Abstract

The emergence and ensuing dominance of COVID-19 on the world stage has emphasized the urgency of efficient animal models for the development of therapeutics for and assessment of immune responses to SARS-CoV-2 infection. Shortcomings of current animal models for SARS-CoV-2 include limited lower respiratory disease, divergence from clinical COVID-19 disease, and requirements for host genetic modifications to permit infection. In this study, n = 12 specific-pathogen-free domestic cats were infected intratracheally with SARS-CoV-2 to evaluate clinical disease, histopathologic lesions, and viral infection kinetics at 4 and 8 days post-inoculation; n = 6 sham-inoculated cats served as controls. Intratracheal inoculation of SARS-CoV-2 produced a significant degree of clinical disease (lethargy, fever, dyspnea, and dry cough) consistent with that observed in the early exudative phase of COVID-19. Pulmonary lesions such as diffuse alveolar damage, hyaline membrane formation, fibrin deposition, and proteinaceous exudates were also observed with SARS-CoV-2 infection, replicating lesions identified in people hospitalized with ARDS from COVID-19. A significant correlation was observed between the degree of clinical disease identified in infected cats and pulmonary lesions. Viral loads and ACE2 expression were also quantified in nasal turbinates, distal trachea, lungs, and other organs. Results of this study validate a feline model for SARS-CoV-2 infection that results in clinical disease and histopathologic lesions consistent with acute COVID-19 in humans, thus encouraging its use for future translational studies.

Highlights

  • Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)in late 2019, Coronavirus Disease 2019 (COVID-19) has swept across the globe, resulting in over 4 million deaths worldwide as of July 2021 [1]

  • A wide range of clinical symptoms are reported, mortality of COVID-19 patients is closely correlated with progression of viral infection to severe lung disease and respiratory failure due to acute respiratory distress syndrome (ARDS), which is further complicated by immune cell dyscrasias and hyperinflammation in critically ill patients [2,3,4]

  • In order to clinically assess the feline model in Animal Biosafety Level-3 conditions, a clinical scoring system for feline respiratory disease was developed by integrating features of previously utilized systems [47,48,49] (Table 1)

Read more

Summary

Introduction

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)in late 2019, Coronavirus Disease 2019 (COVID-19) has swept across the globe, resulting in over 4 million deaths worldwide as of July 2021 [1]. Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A wide range of clinical symptoms are reported, mortality of COVID-19 patients is closely correlated with progression of viral infection to severe lung disease (pneumonia) and respiratory failure due to acute respiratory distress syndrome (ARDS), which is further complicated by immune cell dyscrasias and hyperinflammation (cytokine storm) in critically ill patients [2,3,4]. Animal model that parallels clinical and pathologic features of disease in addition to route of infection, replication, and transmission kinetics is of paramount importance. SARS-CoV-2 viral infection and replication within a host requires the presence and distribution of angiotensin-converting enzyme 2 (ACE2) receptors similar to humans [7].

Objectives
Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call