Prolonged immune activation in post-acute sequelae of SARS-CoV-2: neutrophil dynamics and therapeutic insights

To comprehensively understand the mechanisms driving PASC, we utilized a Phodopus roborovskii hamster model to investigate the long-term effects of SARS-CoV-2 infection compared to Influenza A virus (IAV), showing impaired weight recovery, severe lung pathology, and significant neutrophil accumulation. At 30 dpi, single cell RNA sequencing of BALF, lung, and spleen revealed unique PASC gene signatures, with increased neutrophils and reduced macrophages indicating disrupted myeloid differentiation. Inhibition of neutrophil-driven inflammation reduced PASC symptoms. We utilized a Phodopus roborovskii hamster model to investigate the long-term effects of SARS-CoV-2 infection compared to Influenza A virus (IAV), showing impaired weight recovery, severe lung pathology, and significant neutrophil accumulation. We performed single-cell RNA sequencing on BALF, lung, spleen at 30dpi and histopathological examinations. Our analysis provide critical insights into PASC mechanisms.