Persistent Lung Inflammation and Fibrosis After Mouse-Adapted Omicron BA.1 Infection

As such, the development of animal models that provoke acute and chronic disease phenotypes are essential for understanding disease mechanisms and for development of interventional countermeasures. To address this, we infected aged BALB/c with mouse-adapted SARS-CoV-2 Omicron BA.1 virus (BA.1 MA) which resulted in significant weight loss, reduced lung function, and anosmia during acute disease phase.

We observed viral RNA in sustentacular cells in the upper nasal airways, club cells in lower bronchiolar airways, and alveolar type 2 epithelial cells (AT2 cells) in the alveolar parenchyma. Four months post-infection, post-acute lung pathology was observed that was characteristic of an organized pneumonia with inflammatory infiltrates, tertiary lymphoid structures, and fibrotic lesions. Highly multiplexed immunostaining and spatial transcriptomics indicate the molecular signature of the post-acute fibrotic lesion is consistent with idiopathic fibrosis.