Glucagon-like peptide-1 receptor agonist prevents pulmonary fibrosis following acute COVID-19 infection associated with type 2 diabetes

Although type 2 diabetes (T2D) is associated with PASC, the mechanism of T2D-mediated PASC in lung remains elusive. Here we found that people with T2D (PWT2D) exhibited significantly upregulated fibrosis-related genes in monocytes, which correlated positively with pulmonary fibrosis-related biomarkers up to 3 months after acute SARS-CoV-2 infection.

Using db/db mice to model human T2D, we found consistently that SARS-CoV-2 infection resulted in upregulation of fibrosis-related genes in lung macrophages and persistent pulmonary fibrosis. Moreover, the macrophage-depletion demonstrated that proinflammatory macrophages in db/db mice were determinants for inducing the pulmonary fibrosis post-infection. Importantly, the anti-T2D glucagon-like peptide-1 receptor agonist (GLP-1RA) reprogramed macrophage responses to SARS-CoV-2 by normalizing fibrosis-related genes, significantly reducing the pulmonary fibrosis in a glucose-independent manner.