Vasculitis and Neutrophil Extracellular Traps in Lungs of Golden Syrian Hamsters With SARS-CoV-2

Abstract

Neutrophil extracellular traps (NETs) have been identified as one pathogenetic trigger in severe COVID-19 cases and therefore well-described animal models to understand the influence of NETs in COVID-19 pathogenesis are needed. SARS-CoV-2 infection causes infection and interstitial pneumonia of varying severity in humans and COVID-19 models. Pulmonary as well as peripheral vascular lesions represent a severe, sometimes fatal, disease complication of unknown pathogenesis in COVID-19 patients. Furthermore, neutrophil extracellular traps (NETs), which are known to contribute to vessel inflammation or endothelial damage, have also been shown as potential driver of COVID-19 in humans. Though most studies in animal models describe the pulmonary lesions characterized by interstitial inflammation, type II pneumocyte hyperplasia, edema, fibrin formation and infiltration of macrophages and neutrophils, detailed pathological description of vascular lesions or NETs in COVID-19 animal models are lacking so far. Here we report different types of pulmonary vascular lesions in the golden Syrian hamster model of COVID-19. Vascular lesions included endothelialitis and vasculitis at 3 and 6 days post infection (dpi), and were almost nearly resolved at 14 dpi. Importantly, virus antigen was present in pulmonary lesions, but lacking in vascular alterations. In good correlation to these data, NETs were detected in the lungs of infected animals at 3 and 6 dpi. Hence, the Syrian hamster seems to represent a useful model to further investigate the role of vascular lesions and NETs in COVID-19 pathogenesis.

Abnormal Blood Coagulation and Kidney Damage in Aged Hamsters Infected with Severe Acute Respiratory Syndrome Coronavirus 2

“…Furthermore, the absence of viral antigens in the vascular endothelium at any time point suggests that virus infection or replication is not the direct cause of vasculitis or intravascular blood clotting in the lungs of infected hamsters. This notion is supported by a previous report showing the involvement of not the virus itself but neutrophil extracellular traps (NETs) in vasculitis in the lung using the hamster COVID-19 model [25]. Recently, our group reported a critical role of LOX-1 in thrombin generation and lung thrombosis in a severe influenza mouse model [17].…”

Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents

“…Detection of SARS-CoV-2 nucleocapsid protein was performed on formalin-fixed, paraffin-embedded hamster lung tissue using a monoclonal mouse antibody (Sino Biological, 40143-MM0) and the Dako EnVision+ polymer system (Dako Agilent Pathology Solutions) as described ( 52 ). Evaluation was performed semiquantitatively for the alveoli and the airway epithelium (0 = no antigen; 1 = minimal, single foci, less than 1% of tissue affected, 2 = mild, 2-25%, 3 = moderate, 26-50%, 4 = severe, 51-75%, 5 = subtotal, >75%).…”

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 .…”