Abstract
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.
Highlights
Characterization and quantification of pulmonary vascular alterations were performed in golden Syrian hamsters experimentally infected with SARS-CoV-2 (Figure 2)
The present study showed that SARS-CoV-2 infection leads to vascular alterations including endothelial hypertrophy, vasculitis, endothelialitis, and associated vascular leakage
Further analyses revealed that inflammatory vascular changes resulted in the formation of perivascular edema accompanied by the loss of aquaporin 1 (AQP1) water channels
Summary
A total of 30% of the SARS-CoV-2 infected patients suffer from a severe clinical course with alveolar and vascular damage resulting in the activation of coagulation pathways and a consecutive disseminated intravascular coagulation [2,4,5]. Alveolar damage represents a rather nonspecific feature of pulmonary disease and can be attributed to a variety of respiratory viruses such as Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and influenza A viruses. Examinations of lungs from patients who died from COVID-19 indicate that the recruitment of inflammatory cells either represents a direct result of viral infection or a solely immune-mediated feature, which may induce diffuse endothelial inflammation with dysfunction and apoptosis [2,5,8]
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