Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment.
Cell
; 182(3): 734-743.e5, 2020 08 06.
Article
in En
| MEDLINE
| ID: mdl-32643603
ABSTRACT
COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells, and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly IC and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis and to evaluate new therapies and vaccines.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Vaccination
/
Coronavirus Infections
/
Disease Models, Animal
/
Pandemics
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Betacoronavirus
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Year:
2020
Type:
Article