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Multi-Organ Histopathological Changes in a Mouse Hepatitis Virus Model of COVID-19.
Paidas, Michael J; Mohamed, Adhar B; Norenberg, Michael D; Saad, Ali; Barry, Ariel Faye; Colon, Cristina; Kenyon, Norma Sue; Jayakumar, Arumugam R.
  • Paidas MJ; Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Miami, Miami, FL 33136, USA.
  • Mohamed AB; Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Miami, Miami, FL 33136, USA.
  • Norenberg MD; Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
  • Saad A; Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
  • Barry AF; Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Miami, Miami, FL 33136, USA.
  • Colon C; Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Miami, Miami, FL 33136, USA.
  • Kenyon NS; Microbiology & Immunology and Biomedical Engineering, Diabetes Research Institute, University of Miami, Miami, FL 33136, USA.
  • Jayakumar AR; Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Miami, Miami, FL 33136, USA.
Viruses ; 13(9)2021 08 27.
Article in English | MEDLINE | ID: covidwho-1374535
ABSTRACT
Infection with SARS-CoV-2, the virus responsible for the global COVID-19 pandemic, causes a respiratory illness that can severely impact other organ systems and is possibly precipitated by cytokine storm, septic shock, thrombosis, and oxidative stress. SARS-CoV-2 infected individuals may be asymptomatic or may experience mild, moderate, or severe symptoms with or without pneumonia. The mechanisms by which SARS-CoV-2 infects humans are largely unknown. Mouse hepatitis virus 1 (MHV-1)-induced infection was used as a highly relevant surrogate animal model for this study. We further characterized this animal model and compared it with SARS-CoV-2 infection in humans. MHV-1 inoculated mice displayed death as well as weight loss, as reported earlier. We showed that MHV-1-infected mice at days 7-8 exhibit severe lung inflammation, 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 red blood cells), mononuclear cell infiltration, hyaline membrane formation, the presence of hemosiderin-laden macrophages, and interstitial edema. When compared to uninfected mice, the infected mice showed severe liver vascular congestion, luminal thrombosis of portal and sinusoidal vessels, hepatocyte degeneration, cell necrosis, and hemorrhagic changes. Proximal and distal tubular necrosis, hemorrhage in interstitial tissue, and the vacuolation of renal tubules were observed. The heart showed severe interstitial edema, vascular congestion, and dilation, as well as red blood cell extravasation into the interstitium. Upon examination of the MHV-1 infected mice brain, we observed congested blood vessels, perivascular cavitation, cortical pericellular halos, vacuolation of neuropils, darkly stained nuclei, pyknotic nuclei, and associated vacuolation of the neuropil in the cortex, as well as acute eosinophilic necrosis and necrotic neurons with fragmented nuclei and vacuolation in the hippocampus. Our findings suggest that the widespread thrombotic events observed in the surrogate animal model for SARS-CoV-2 mimic the reported findings in SARS-CoV-2 infected humans, representing a highly relevant and safe animal model for the study of the pathophysiologic mechanisms of SARS-CoV-2 for potential therapeutic interventions.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Infections / Murine hepatitis virus Type of study: Prognostic study Limits: Animals / Female / Humans Language: English Year: 2021 Document Type: Article Affiliation country: V13091703

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Infections / Murine hepatitis virus Type of study: Prognostic study Limits: Animals / Female / Humans Language: English Year: 2021 Document Type: Article Affiliation country: V13091703