Sustained Lung Inflammation Post‐SARS‐CoV‐2 Infection in Mice Is Associated with Increased Pulmonary T Cells

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 × 10 2 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.