GEOTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE286940GEOGSEfalseGlucagon-like peptide-1 receptor agonist prevents pulmonary post-acute sequelae of COVID-19 associated with type 2 diabetesPost-acute sequelae of COVID-19 (PASC) posts a major health burden after SARS-CoV-2 infection. 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. These findings demonstrated that SARS-CoV-2-induced proinflammatory macrophages are detrimental factors in T2D-mediated PASC, which can be prevented by GLP-1RA.2026/06/01GSE286940GSM8734585GSM8734584GSM8734583GSM8734582GSM873458124247286940Mus musculus