Absence of COVID-19-associated changes in plasma coagulation proteins and pulmonary thrombosis in the ferret model

Iris C. Kreft, Roy R.A. Winiarczyk, Dutch Covid-19 and Thrombosis Coalition (DCTC), Fric J. Tanis, Carmen van der Zwaan, Katharina S. Schmitz, Arie J. Hoogendijk, Rik L. de Swart, Anne Moscona, Matteo Porotto, Daniela C.F. Salvatori, Rory D. de Vries, Moniek P.M. de Maat, Maartje van den Biggelaar, Bart J.M. van Vlijmen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)6-11
Number of pages6
JournalThrombosis Research
Early online date20 Dec 2021
Publication statusPublished - 1 Feb 2022

Bibliographical note

Funding Information:
The Dutch Covid-19 and Thrombosis Coalition (DCTC) is supported by grants from the Dutch Thrombosis Foundation and The Netherlands Organization for Health Research and Development (ZON-MW) . Ferret studies were supported by funding from the National Institutes of Health ( AI146980 , AI121349 , NS091263 , AI114736 ), and a Harrington Discovery Institute COVID-19 award. We thank Erna Peters, Reshma Lalai (LUMC), Mart Lamers, Anna Mykytyn, Sander Herfst, Elwin Verveer, Danny Noack, Barry Rockx and Marion Koopmans (Erasmus MC) for their contributions to this study. We thank Prof. Dr. C. Drosten who kindly provided SARS-CoV-2 isolate BetaCoV/Munich/BavPat1/2020.

Publisher Copyright:
© 2021


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