COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice

Jian Zheng, Lok-Yin Roy Wong, Kun Li, Abhishek Kumar Verma, Miguel E. Ortiz, Christine Wohlford-Lenane, Mariah R. Leidinger, C. Michael Knudson, David K. Meyerholz, Paul B. McCray () and Stanley Perlman ()
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Jian Zheng: University of Iowa
Lok-Yin Roy Wong: University of Iowa
Kun Li: University of Iowa
Abhishek Kumar Verma: University of Iowa
Miguel E. Ortiz: University of Iowa
Christine Wohlford-Lenane: University of Iowa
Mariah R. Leidinger: University of Iowa
C. Michael Knudson: University of Iowa
David K. Meyerholz: University of Iowa
Paul B. McCray: University of Iowa
Stanley Perlman: University of Iowa

Nature, 2021, vol. 589, issue 7843, 603-607

Abstract: Abstract The ongoing coronavirus disease 2019 (COVID-19) pandemic is associated with substantial morbidity and mortality. Although much has been learned in the first few 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 anosmia show no or only minor respiratory symptoms1. Studies in animals infected experimentally with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, provide opportunities to study aspects of the disease that are not easily investigated in human patients. Although the severity of COVID-19 ranges from asymptomatic to lethal2, most experimental infections provide insights into mild disease3. Here, using K18-hACE2 transgenic mice that were originally developed for SARS studies4, 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. Furthermore, we show that infusion of convalescent plasma from a recovered patient with COVID-19 protected against lethal disease. Mice developed anosmia at early time points after infection. Notably, although pre-treatment with convalescent plasma prevented most signs of clinical disease, it did not prevent anosmia. Thus, K18-hACE2 mice provide a useful model for studying the pathological basis of both mild and lethal COVID-19 and for assessing therapeutic interventions.

Date: 2021
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DOI: 10.1038/s41586-020-2943-z

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