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Multi-organ Vascular Defects and General Morphological Changes in a Murine Model of SARS CoV-2 Infection

M. Paidas1, A. Mohamed1, A. Saad2, A. Jayakumar1

1Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami, Miami, United States, 2Department of Pathology, University of Miami, Miami, United States

Abstract Number: PB0150

Meeting: ISTH 2021 Congress

Theme: COVID and Coagulation » COVID and Coagulation, Basic Science

Background: Infection with SARS-CoV-2, the virus responsible for the Covid-19 global pandemic, causes a respiratory illness and can severely impact other organ systems, possibly precipitated by cytokine storm, septic shock, thrombosis and oxidative/nitrative stress. SARS-CoV-2 infected individuals may be asymptomatic or may experience mild, moderate, or severe symptoms with or without pneumonia.

Aims: The mechanisms by which SARS-CoV-2 infect humans is largely unknown.

Methods: Murine Hepatitis Virus 1 infusion in mice was used in this study which is a highly relevant and surrogate animal model for SARS-CoV-2.

Results: We found that MHV-1-induced animal death (60%), as well as weight loss. MHV-1-infected mice at day 7-8 showed thrombi of pulmonary vessels, arterial endothelial swelling, inflammation and granular degeneration of vascular endothelial cells, and margination of leukocytes into the interstitium. Furthermore, peribronchiolar interstitial infiltration, bronchiolar epithelial cell necrosis and intra-alveolar necrotic debris, alveolar exudation (surrounding alveolar walls have capillaries that are dilated and filled with RBCs), mononuclear cell infiltration, hyaline membrane formation and interstitial edema were also observed in these mice. When compared to those uninfected, infected mice showed severe liver vascular congestion, luminal thrombosis of portal and sinusoidal vessels, hepatocytes degeneration, cells necrosis and hemorrhagic changes. Acute tubular necrosis and thrombosis were observed in the kidney. The heart also showed thrombosis, severe interstitial edema, vascular congestion and dilation, and red blood cells extravasation into interstitium.

Conclusions: Our findings suggest that the widespread thrombosis seen in highly relevant and surrogate animal model for SARS-CoV-2 mimics the reported findings in SARS-CoV-2-infected humans and represents an attractive, safer, animal model to study SARS-CoV-2 infection, pathophysiologic mechanisms and potential therapeutic interventions.

To cite this abstract in AMA style:

Paidas M, Mohamed A, Saad A, Jayakumar A. Multi-organ Vascular Defects and General Morphological Changes in a Murine Model of SARS CoV-2 Infection [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/multi-organ-vascular-defects-and-general-morphological-changes-in-a-murine-model-of-sars-cov-2-infection/. Accessed June 25, 2022.

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