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
Lisa Allnoch,
Georg Beythien,
Eva Leitzen,
Kathrin Becker,
Franz-Josef Kaup,
Stephanie Stanelle-Bertram,
Berfin Schaumburg,
Nancy Mounogou Kouassi,
Sebastian Beck,
Martin Zickler,
Vanessa Herder,
Gülsah Gabriel,
Wolfgang Baumgärtner
Affiliations
Lisa Allnoch
Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Georg Beythien
Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Eva Leitzen
Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Kathrin Becker
Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Franz-Josef Kaup
Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Stephanie Stanelle-Bertram
Department for Viral Zoonoses-One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany
Berfin Schaumburg
Department for Viral Zoonoses-One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany
Nancy Mounogou Kouassi
Department for Viral Zoonoses-One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany
Sebastian Beck
Department for Viral Zoonoses-One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany
Martin Zickler
Department for Viral Zoonoses-One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany
Vanessa Herder
Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Gülsah Gabriel
Department for Viral Zoonoses-One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany
Wolfgang Baumgärtner
Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
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.
