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K18-hACE2 Mice for Studies of COVID-19 Treatments and Pathogenesis Including Anosmia

Jian Zheng, Lok-Yin Roy Wong, Kun Li, Abhishek K. Verma, View ORCID ProfileMiguel Ortiz, Christine Wohlford-Lenane, Mariah R. Leidinger, C. Michael Knudson, David K. Meyerholz, Paul B. McCray Jr., Stanley Perlman
doi: https://doi.org/10.1101/2020.08.07.242073
Jian Zheng
1Departments of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
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Lok-Yin Roy Wong
1Departments of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
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Kun Li
2Departments of Pathology,University of Iowa, Iowa City, Iowa, USA
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Abhishek K. Verma
1Departments of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
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Miguel Ortiz
2Departments of Pathology,University of Iowa, Iowa City, Iowa, USA
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  • ORCID record for Miguel Ortiz
Christine Wohlford-Lenane
2Departments of Pathology,University of Iowa, Iowa City, Iowa, USA
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Mariah R. Leidinger
3Departments of Pediatrics, University of Iowa, Iowa City, Iowa, USA
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C. Michael Knudson
3Departments of Pediatrics, University of Iowa, Iowa City, Iowa, USA
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David K. Meyerholz
3Departments of Pediatrics, University of Iowa, Iowa City, Iowa, USA
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Paul B. McCray Jr.
1Departments of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
2Departments of Pathology,University of Iowa, Iowa City, Iowa, USA
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  • For correspondence: stanley-perlman@uiowa.edu paul-mccray@uiowa.edu
Stanley Perlman
1Departments of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
2Departments of Pathology,University of Iowa, Iowa City, Iowa, USA
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  • For correspondence: stanley-perlman@uiowa.edu paul-mccray@uiowa.edu
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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.

Competing Interest Statement

The authors have declared no competing interest.

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Posted August 10, 2020.
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K18-hACE2 Mice for Studies of COVID-19 Treatments and Pathogenesis Including Anosmia
Jian Zheng, Lok-Yin Roy Wong, Kun Li, Abhishek K. Verma, Miguel Ortiz, Christine Wohlford-Lenane, Mariah R. Leidinger, C. Michael Knudson, David K. Meyerholz, Paul B. McCray Jr., Stanley Perlman
bioRxiv 2020.08.07.242073; doi: https://doi.org/10.1101/2020.08.07.242073
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K18-hACE2 Mice for Studies of COVID-19 Treatments and Pathogenesis Including Anosmia
Jian Zheng, Lok-Yin Roy Wong, Kun Li, Abhishek K. Verma, Miguel Ortiz, Christine Wohlford-Lenane, Mariah R. Leidinger, C. Michael Knudson, David K. Meyerholz, Paul B. McCray Jr., Stanley Perlman
bioRxiv 2020.08.07.242073; doi: https://doi.org/10.1101/2020.08.07.242073

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