K18-hACE2 mice develop respiratory disease resembling severe COVID-19.

BioRxiv : the Preprint Server for Biology
C. K. YindaVincent J Munster

Abstract

SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 [hACE2]) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 10 4 TCID 50 or 10 5 TCID 50 , the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 10 5 TCID 50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that re...Continue Reading

Citations

Oct 20, 2020·Emerging Microbes & Infections·Raveen RathnasingheMelissa B Uccellini
May 7, 2021·Scientific Reports·C Joaquín CáceresDaniel R Perez

Methods Mentioned

BETA
transgenic
ELISA
enzyme-linked immunosorbent assay

Related Concepts

Related Feeds

American Thoracic Society: Clinical Problems

This feed has been developed in conjunction with the American Thoracic Society for the benefit of its Clinical Problems Assembly. It highlights new and impactful papers on clinical therapeutics, diagnoses, and practices pertaining to respiratory disease.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

American Thoracic Society: Allergy, Immunology & Inflammation

This feed has been developed in conjunction with the American Thoracic Society for the benefit of its Allergy, Immunology, and Inflammation Assembly. It highlights new and impactful papers on allergy, asthma, genetics, and the pathogenesis of lung diseases.