COVID-19 Treatments and Pathogenesis Including Anosmia in K18-hACE2 mice

Zheng, Jian; Wong, Lok-Yin Roy; Li, Kun; Verma, Abhishek Kumar; Ortiz, Miguel; Wohlford-Lenane, Christine; Leidinger, Mariah R.; Knudson, C. Michael; Meyerholz, David K.; McCray, Paul B.; Perlman, Stanley

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(1). 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. While COVID-19 severity ranges from asymptomatic to lethal(2), most experimental infections provide insights into mild disease(3). Here, using K18-hACE2 mice that we originally developed for SARS studies(4), 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 protected against lethal disease. Mice developed anosmia at early times after infection. Notably, while pretreatment 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.