Vascular Inflammation Is Associated with Loss of Aquaporin 1 Expression on Endothelial Cells and Increased Fluid Leakage in SARS-CoV-2 Infected Golden Syrian Hamsters

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.

Modeling SARS-CoV-2: Comparative Pathology in Rhesus Macaque and Golden Syrian Hamster Models

“… 35 This finding indicates that vascular lesions in hamsters are not the direct consequence of viral infection of endothelial cells but likely represent the consequence of immune-mediated effects from infiltrating immune cells. Allnoch et al 36 recently showed that the circumferential loss of aquaporin 1 is associated with disruption of vascular endothelium in hamsters and may contribute to the loss of intercellular junctions, leading to perivascular edema and other vascular changes in SARS-CoV-2 infection.…”

Cellular tropism of SARS-CoV-2 in the respiratory tract of Syrian hamsters and B6.Cg-Tg(K18-ACE2)2Prlmn/J transgenic mice

“… 11 , 50 A recent ultrastructural examination of the endothelium of the hamster lungs supports this hypothesis as it showed there was damage to the endothelium without the presence of virus. 1 …”

The Upper Respiratory Tract of Felids Is Highly Susceptible to SARS-CoV-2 Infection

“…In addition, immunohistochemistry was performed on formalin-fixed, paraffin-embedded (FFPE) samples using the avidin–biotin–peroxidase complex (ABC; Vector Laboratories, Burlingame, CA, USA) method as previously described [ 49 , 50 ]. Primary antibodies targeting caspase-3, CD204 (PCLS), α-tubulin, and ki67 and secondary antibodies are listed in Supplementary Material Table S2 .…”