Abstract
BackgroundMany 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.ObjectivesThis 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 methodsHistology and longitudinal plasma profiling using mass spectrometry-based proteomics approach was performed.ResultsLungs 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.ConclusionsWe 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
Many patients who are diagnosed with COVID-19 suffer from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-induced thrombo(embolic) complications
Lung material and plasma from these SARS-CoV-2-inoculated donor ferrets were analysed for COVID-19-associated changes in coagulation and thrombosis using histology and mass spectrometry (MS)-based proteomics
Plasma and lung samples were collected from Influenza virus, SARS-CoV-2 and Aleutian Disease Virus seronegative young adult male ferrets (M. putorius furo) that were obtained from a commercial breeder (Triple F Farms, PA, USA), and were part of a recent study on intranasal fusion inhibitory lipopeptides in preventing direct-contact SARS-CoV-2 trans mission [8]
Summary
Many patients who are diagnosed with COVID-19 suffer from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-induced thrombo(embolic) complications. Klok et al [1] studied the incidence of venous thromboembolisms (VTE) among COVID-19 patients in intensive care units (ICU), showing that despite daily administration of antico agulants, over 30% of these COVID-19 patients developed thrombo(embolic) complications This was significantly higher compared to nonCOVID ICU patients, indicating that SARS-CoV-2 may induce a strong pro-thrombotic trigger [2]. Lung material and plasma from these SARS-CoV-2-inoculated donor ferrets were analysed for COVID-19-associated changes in coagulation and thrombosis using histology and mass spectrometry (MS)-based proteomics. The latter approach allows for the simultaneous identification and quantification of hundreds of plasma proteins, including hemostatic and inflammatory signatures in human [9], and was used for ferrets, a species for which very limited protein (immuno) assays are available. In contrast to activity- and immune-proteins assays, MS-based prote omics may be successfully used for (ferret)plasma that has been subjected to a heat-inactivation step necessary to abolish infectivity of the potentially hazardous plasma
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