Vascular changes represent a characteristic feature of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection leading to a breakdown of the vascular barrier and subsequent edema formation. The aim of this study was to provide a detailed characterization of the vascular alterations during SARS-CoV-2 infection and to evaluate the impaired vascular integrity. Groups of ten golden Syrian hamsters were infected intranasally with SARS-CoV-2 or phosphate-buffered saline (mock infection). Necropsies were performed at 1, 3, 6, and 14 days post-infection (dpi). Lung samples were investigated using hematoxylin and eosin, alcian blue, immunohistochemistry targeting aquaporin 1, CD3, CD204, CD31, laminin, myeloperoxidase, SARS-CoV-2 nucleoprotein, and transmission electron microscopy. SARS-CoV-2 infected animals showed endothelial hypertrophy, endothelialitis, and vasculitis. Inflammation mainly consisted of macrophages and lower numbers of T-lymphocytes and neutrophils/heterophils infiltrating the vascular walls as well as the perivascular region at 3 and 6 dpi. Affected vessels showed edema formation in association with loss of aquaporin 1 on endothelial cells. In addition, an ultrastructural investigation revealed disruption of the endothelium. Summarized, the presented findings indicate that loss of aquaporin 1 entails the loss of intercellular junctions resulting in paracellular leakage of edema as a key pathogenic mechanism in SARS-CoV-2 triggered pulmonary lesions.
【저자키워드】 COVID-19, SARS-CoV-2, Endothelium, Vasculitis, hamster, Vasculopathy, aquaporin 1, perivascular edema, 【초록키워드】 Macrophage, immunohistochemistry, SARS-COV-2 infection, Infection, endothelial cells, edema, group, characteristic, transmission electron microscopy, mechanism, association, Coronavirus-2, myeloperoxidase, T-lymphocyte, endothelial, acute respiratory syndrome, Hematoxylin and eosin, phosphate-buffered saline, Vascular, alteration, necropsy, pulmonary lesions, pathogenic, SARS-CoV-2 nucleoprotein, CD31, CD3, vessel, junction, resulting, performed, were infected, evaluate, intranasally, subsequent, addition, investigated, triggered, infiltrating, days post-infection, perivascular, intercellular, Vascular change, 【제목키워드】 leakage, Loss, aquaporin, Increased,