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K18-hACE2 Mice for Studies of COVID-19 Treatments and Pathogenesis Including Anosmia
Stanley Perlman; Jian Zheng; LOK YIN ROY WONG; Kun Li; Abhishek K Verma; Miguel E Ortiz Bezara; Christine Wohlford-Lenane; Mariah R. Leidinger; Michael C. Kundson; David K. Meyerholz; Paul B McCray Jr..
Afiliación
  • Stanley Perlman; University of Iowa
  • Jian Zheng; University of Iowa
  • LOK YIN ROY WONG; University of Iowa
  • Kun Li; University of Iowa
  • Abhishek K Verma; University of Iowa
  • Miguel E Ortiz Bezara; University of Iowa
  • Christine Wohlford-Lenane; University of Iowa
  • Mariah R. Leidinger; University of Iowa
  • Michael C. Kundson; University of Iowa
  • David K. Meyerholz; University of Iowa
  • Paul B McCray Jr.; University of Iowa
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-242073
ABSTRACT
The ongoing COVID-19 pandemic is associated with substantial morbidity and mortality. While much has been learned in the first months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation and many patients with this finding show no or only minor respiratory signs. Studies in animals experimentally infected with SARS-CoV-2, the cause of COVID-19, provide opportunities to study aspects of the disease not easily investigated in human patients. COVID-19 severity ranges from asymptomatic to lethal. Most experimental infections provide insights into mild disease. Here, using K18-hACE2 mice that we originally developed for SARS studies, we show that infection with SARS-CoV-2 causes severe disease in the lung, and in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Further, we show that infusion of convalescent plasma (CP) from a recovered COVID-19 patient provided protection against lethal disease. Mice developed anosmia at early times after infection. Notably, while treatment with CP prevented significant clinical disease, it did not prevent anosmia. Thus K18-hACE2 mice provide a useful model for studying the pathological underpinnings of both mild and lethal COVID-19 and for assessing therapeutic interventions.
Licencia
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2020 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2020 Tipo del documento: Preprint