Recruitment of pulmonary intravascular macrophages in SARS-CoV-2 infected hamsters.

The mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe lung inflammation and mortality remain unclear. While the role of alveolar macrophages in COVID-19 is known, data on pulmonary intravascular macrophages (PIMs) is lacking. PIMs are key inflammatory cells present in species like cattle and pigs. Though constitutively absent in humans and rodents, their recruitment in rodents triggers exaggerated inflammation. We investigated the recruitment of PIMs and other immune cells, using immunofluorescence, hematoxylin and eosin (H&E) staining, and immunogold labeling in a hamster model of SARS-CoV-2 infection. Syrian golden hamsters were divided into 6 groups: uninfected control, unvaccinated-infected at 2-, 5-, and 14-days post infection (dpi) and vaccinated-infected at 5- and 14-dpi. Lung tissues were analyzed for neutrophils (myeloperoxidase), monocytes/macrophages (CCR2, CX3CR1), macrophages (IBA-1), and T cells (CD3). Septal macrophages increased at 2-, 5-, and 14-dpi in infected animals vs. control. CX3CR1 + cells decreased at 14-dpi in unvaccinated animals, but CX3CR1/CCR2 double positive cells were higher at 5-dpi, indicating a pro-inflammatory macrophage phenotype. PIMs were confirmed by transmission electron microscopy. These are the first data showing recruitment of pro-inflammatory PIMs in SARS-CoV-2 infected lungs.