Absence of COVID-19-associated changes in plasma coagulation proteins and pulmonary thrombosis in the ferret model.
COVID-19
Ferrets
Mass spectrometry
Proteomics
Thrombosis
Journal
Thrombosis research
ISSN: 1879-2472
Titre abrégé: Thromb Res
Pays: United States
ID NLM: 0326377
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
04
10
2021
revised:
29
11
2021
accepted:
16
12
2021
pubmed:
27
12
2021
medline:
10
2
2022
entrez:
26
12
2021
Statut:
ppublish
Résumé
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. 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. Histology and longitudinal plasma profiling using mass spectrometry-based proteomics approach was performed. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 34954402
pii: S0049-3848(21)00574-0
doi: 10.1016/j.thromres.2021.12.015
pmc: PMC8690567
pii:
doi:
Substances chimiques
Blood Proteins
0
Types de publication
Journal Article
Comment
Langues
eng
Sous-ensembles de citation
IM
Pagination
6-11Subventions
Organisme : NIAID NIH HHS
ID : R01 AI121349
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS091263
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI146980
Pays : United States
Commentaires et corrections
Type : CommentOn
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
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