Absence of COVID-19-associated changes in plasma coagulation proteins and pulmonary thrombosis in the ferret model. Issue 210 (February 2022)

• Record Type: Journal Article
• Authors: Kreft, Iris C.; Winiarczyk, Roy R.A.; Tanis, Fric J.; van der Zwaan, Carmen; Schmitz, Katharina S.; Hoogendijk, Arie J.; de Swart, Rik L.; Moscona, Anne; Porotto, Matteo; Salvatori, Daniela C.F.; de Vries, Rory D.; de Maat, Moniek P.M.; van den Biggelaar, Maartje; van Vlijmen, Bart J.M.
• Is Part Of: Thrombosis research. Issue 210(2022)
• Page Start: 6
• Page End: 11
• Publication Date: 2022-02
• Subjects: COVID-19 -- Ferrets -- Mass spectrometry -- Proteomics -- Thrombosis; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2021.12.015
• Languages: English
• ISSNs: 0049-3848

Abstract

Summary: Background: Many patients who are diagnosed with coronavirus disease 2019 (COVID-19) suffer from venous thromboembolic complications despite the use of stringent anticoagulant prophylaxis. Studies on the exact mechanism(s) underlying thrombosis in COVID-19 are limited as animal models commonly used to study venous thrombosis pathophysiology ( i.e. rats and mice) are naturally not susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Ferrets are susceptible to SARS-CoV-2 infection, successfully used to study virus transmission, and have been previously used to study activation of coagulation and thrombosis during influenza virus infection. Objectives: This study aimed to explore the use of (heat-inactivated) plasma and lung material from SARS-CoV-2-inoculated ferrets studying COVID-19-associated changes in coagulation and thrombosis. Material and methods: Histology and longitudinal plasma profiling using mass spectrometry-based proteomics approach was performed. Results: Lungs of ferrets inoculated intranasally with SARS-CoV-2 demonstrated alveolar septa that were mildly expanded by macrophages, and diffuse interstitial histiocytic pneumonia. However, no macroscopical or microscopical evidence of vascular thrombosis in the lungs of SARS-CoV-2-inoculated ferrets was found. Longitudinal plasma profiling revealed minor differences in plasma protein profiles in SARS-CoV-2-inoculated ferrets up to 2 weeks post-infection. The majority of plasma coagulation factors were stable and demonstrated a low coefficient of variation. Conclusions: We conclude that while ferrets are an essential and well-suited animal model to study SARS-CoV-2 transmission, their use to study SARS-CoV-2-related changes relevant to thrombotic disease is limited. Highlights: COVID-19-associated changes in lung and plasma in coagulation and thrombosis were studied in a ferret model. Lung tissue from SARS-CoV-2-inoculated ferrets showed no evidence of (microvascular) thrombosis. Mass spectrometry analysis showed that plasma coagulation proteins were stable. The value of ferrets to study COVID-19-associated changes in coagulation and thrombosis is limited.