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Authors: Bao et al.

Link to paper:

Journal/ Pre-Print: bioRxiv

Key Words: ACE2, mouse model, transgenic mice, pathology, (5 max)


1. Transgenic mice expressing human ACE2 can be infected with SARS-CoV-2 virus, with significantly increased viral load in lung tissue peaking at 3 days post infection (dpi) and increased anti-spike IgG 21 dpi

2. SARS-CoV-2 infection in ACE2+ mice caused pneumonia, alveolar lesions, increased collagen deposition, detachment of bronchiolar epithelium and infiltration of CD3+ T cells, CD19+ B cells and MAC2+ macrophages, peaking at 5 dpi and becoming milder by 7 dpi

3. This study shows that SARS-CoV-2 meets the requirements of Koch’s postulate to formally identify it as the causative pathogen of COVID-19.


Transgenic mice expressing hACE2 can be infected with SARS-CoV-2. qRT-PCR detected increased viral load in lung tissue, peaking at 3 days post infection (dpi) and increased serum anti-spike IgG at 21 dpi. Lung histopathology indicates alveolar lesions, pneumonia, collagen deposition and infiltration of CD3+ T cells, CD19+ B cells and MAC2+ macrophages, peaking at 5 dpi. hACE2 and SARS-2-S colocalised on alveolar epithelial cells and viral antigens were detected in alveolar macrophages. This study shows SARS-CoV-2 fulfils Koch’s postulate and presents transgenic ACE2+ mice as a potentially effective in vivo model for SARS-CoV-2 infection.


Understand the virology and/or cell biology of SARS-CoV2/COVID19. This study confirms in an in vivo mouse model that ACE2 is required for SARS-2-CoV infection, and it is the necessary attachment receptor.

Others: Provides biological model to facilitate SARS-2-CoV-2/COVID19 research. This transgenic mouse model seems to reliably model human COVID19 and has potential to be used to test vaccines and treatments.


In vivo mouse study


Novelty: The study is the first to formally show that SARS-CoV-2 fulfils Koch’s postulate and is therefore the causative pathogen of COVID-19. It also presents transgenic hACE2+ mice as a novel in vivo model for COVID-19 research.

Standing in the field: The findings are supported by extensive research identifying hACE2 as the attachment receptor for SARS-CoV-2.

Appropriate statistics: Yes, simple statistics (t-test and ANOVA) were used.

Viral model used: Authentic SARS-CoV-2 was used

Translatability: Study does not focus on translatable research.

Main limitations: Although hACE2 was identified as the required attachment receptor, the study did not validate whether the same cellular proteases are used for S protein priming in mice as in humans (TMPRSS2 and CatB/L). If this is not the case it could significantly hinder this model for use in testing treatments for COVID19