Journal article
COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice
Nature (London), Vol.589(7843), pp.603-607
01/2021
DOI: 10.1038/s41586-020-2943-z
PMCID: PMC7855185
PMID: 33166988
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 symptoms
. 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 lethal
, most experimental infections provide insights into mild disease
. Here, using K18-hACE2 transgenic mice that were 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. 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.
Details
- Title: Subtitle
- COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice
- Creators
- Jian Zheng - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USALok-Yin Roy Wong - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USAKun Li - Department of Pediatrics, University of Iowa, Iowa City, IA, USAAbhishek Kumar Verma - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USAMiguel E Ortiz - Department of Pediatrics, University of Iowa, Iowa City, IA, USAChristine Wohlford-Lenane - Department of Pediatrics, University of Iowa, Iowa City, IA, USAMariah R Leidinger - Department of Pathology, University of Iowa, Iowa City, IA, USAC Michael Knudson - Department of Pathology, University of Iowa, Iowa City, IA, USADavid K Meyerholz - Department of Pathology, University of Iowa, Iowa City, IA, USAPaul B McCray Jr - Department of Pediatrics, University of Iowa, Iowa City, IA, USA. paul-mccray@uiowa.eduStanley Perlman - Department of Pediatrics, University of Iowa, Iowa City, IA, USA. stanley-perlman@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.589(7843), pp.603-607
- Publisher
- England
- DOI
- 10.1038/s41586-020-2943-z
- PMID
- 33166988
- PMCID
- PMC7855185
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Grant note
- P30 ES005605 / NIEHS NIH HHS R01 AI129269 / NIAID NIH HHS P01 AI060699 / NIAID NIH HHS P30 DK054759 / NIDDK NIH HHS
- Language
- English
- Date published
- 01/2021
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; The University of Iowa Institute for Vision Research; Pathology; Iowa Neuroscience Institute; Radiation Oncology; Infectious Disease (Pediatrics); Internal Medicine
- Record Identifier
- 9984070429702771
Metrics
48 Record Views