tetano
Editor, Senior Moderator
Nature
. 2020 Nov 9.
doi: 10.1038/s41586-020-2943-z. Online ahead of print.
COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice
Jian Zheng[SUP] 1 [/SUP], Lok-Yin Roy Wong[SUP] 1 [/SUP], Kun Li[SUP] 2 [/SUP], Abhishek Kumar Verma[SUP] 1 [/SUP], Miguel Ortiz[SUP] 2 [/SUP], Christine Wohlford-Lenane[SUP] 2 [/SUP], Mariah R Leidinger[SUP] 3 [/SUP], C Michael Knudson[SUP] 3 [/SUP], David K Meyerholz[SUP] 3 [/SUP], Paul B McCray Jr[SUP] 4 5 [/SUP], Stanley Perlman[SUP] 6 7 [/SUP]
Affiliations
Abstract
The ongoing COVID-19 pandemic is associated with substantial morbidity and mortality. Although 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[SUP]1[/SUP]. Studies in animals experimentally infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, provide opportunities to study aspects of the disease not easily investigated in human patients. Although COVID-19 severity ranges from asymptomatic to lethal[SUP]2[/SUP], most experimental infections provide insights into mild disease[SUP]3[/SUP]. Here, using K18-hACE2 mice that we originally developed for SARS studies[SUP]4[/SUP], 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 times after infection. Notably, although pre-treatment with convalescent plasma prevented notable 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.
. 2020 Nov 9.
doi: 10.1038/s41586-020-2943-z. Online ahead of print.
COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice
Jian Zheng[SUP] 1 [/SUP], Lok-Yin Roy Wong[SUP] 1 [/SUP], Kun Li[SUP] 2 [/SUP], Abhishek Kumar Verma[SUP] 1 [/SUP], Miguel Ortiz[SUP] 2 [/SUP], Christine Wohlford-Lenane[SUP] 2 [/SUP], Mariah R Leidinger[SUP] 3 [/SUP], C Michael Knudson[SUP] 3 [/SUP], David K Meyerholz[SUP] 3 [/SUP], Paul B McCray Jr[SUP] 4 5 [/SUP], Stanley Perlman[SUP] 6 7 [/SUP]
Affiliations
- PMID: 33166988
- DOI: 10.1038/s41586-020-2943-z
Abstract
The ongoing COVID-19 pandemic is associated with substantial morbidity and mortality. Although 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[SUP]1[/SUP]. Studies in animals experimentally infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, provide opportunities to study aspects of the disease not easily investigated in human patients. Although COVID-19 severity ranges from asymptomatic to lethal[SUP]2[/SUP], most experimental infections provide insights into mild disease[SUP]3[/SUP]. Here, using K18-hACE2 mice that we originally developed for SARS studies[SUP]4[/SUP], 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 times after infection. Notably, although pre-treatment with convalescent plasma prevented notable 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.