Document Type

Article

Publication Date

8-1-2025

Keywords

JMG, Animals, COVID-19, SARS-CoV-2, Mice, Lung, Mice, Inbred C57BL, CD8-Positive T-Lymphocytes, Disease Models, Animal, Mice, Transgenic, CD4-Positive T-Lymphocytes, Angiotensin-Converting Enzyme 2, Pneumonia, Humans

JAX Source

Eur J Immunol. 2025;55(8):e70043.

ISSN

1521-4141

PMID

40851359

DOI

https://doi.org/10.1002/eji.70043

Abstract

Many SARS-CoV-2 patients experience chronic pulmonary symptoms and long-term inflammation despite viral clearance. While these clinical manifestations have been linked to the dysregulation of the adaptive immune response, the underlying immunopathology remains poorly understood due to a lack of suitable animal models. To investigate long-term pulmonary consequences of SARS-CoV-2 infection, we used a genetic cross of 129 mice and C57BL/6 (B6)-K18-hACE2 transgene mice, a model previously shown to survive infection. 129xB6-K18-hACE2 mice or littermate controls were infected with a low dose (5 × 102 PFU) of ancestral SARS-CoV-2. Complete viral clearance and full recovery from weight loss occurred by day 8 post-infection. However, prolonged inflammation in the lung and airways persisted up to day 28 post-infection and was associated with the presence of CD4+ and CD8+ T cells, particularly CD8+ effector T cells. This model may therefore prove valuable for further understanding of drivers of long-term lung inflammation and for testing therapeutic strategies and clinically relevant interventions that can target long-term pulmonary inflammation following SARS-CoV-2 infection.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Share

COinS