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Methods Mol Biol ; 2410: 177-192, 2022.
Article in English | MEDLINE | ID: covidwho-1575553


The SARS-CoV-2 pandemic has impacted the health of humanity after the outbreak in Hubei, China in late December 2019. Ever since, it has taken unprecedented proportions and rapidity causing over a million fatal cases. Recently, a robust Syrian golden hamster model recapitulating COVID-19 was developed in search for effective therapeutics and vaccine candidates. However, overt clinical disease symptoms were largely absent despite high levels of virus replication and associated pathology in the respiratory tract. Therefore, we used micro-computed tomography (µCT) to longitudinally visualize lung pathology and to preclinically assess candidate vaccines. µCT proved to be crucial to quantify and noninvasively monitor disease progression, to evaluate candidate vaccine efficacy, and to improve screening efforts by allowing longitudinal data without harming live animals. Here, we give a comprehensive guide on how to use low-dose high-resolution µCT to follow-up SARS-CoV-2-induced disease and test the efficacy of COVID-19 vaccine candidates in hamsters. Our approach can likewise be applied for the preclinical assessment of antiviral and anti-inflammatory drug treatments in vivo.

COVID-19 Vaccines , COVID-19 , Animals , COVID-19/prevention & control , Cricetinae , X-Ray Microtomography
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295942


These proceedings contain the presented papers at the 16th International Meeting on Fully Three-Dimensional Image Reconstruction in Radiology and Nuclear Medicine 2021, which was to be held in Leuven, Belgium, but had to be transformed in a virtual meeting because of the covid-19 pandemic. Fully3D is one of the major forums for presentation of new results in the field of 3D image reconstruction, primarily with applications in x-ray computer tomography, PET and SPECT. Over the life-time of the meeting the focus has shifted to reflect recent developments in the field. Many of the major developments in fully 3D PET and SPECT imaging were first presented at Fully3D, as were the key results for analytic reconstruction methods in cone beam x-ray CT. Similarly, in the 2021 meeting a broad range of topics has been presented. As expected, deep learning methods are being used increasingly: they are used as post-processing tools or incorporated in the reconstruction, often aiming at improved noise and/or artifact suppression.

Nat Commun ; 11(1): 5838, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-933686


Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.

Betacoronavirus/physiology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Disease Models, Animal , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , STAT2 Transcription Factor/metabolism , Signal Transduction , Animals , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/metabolism , Cricetinae , Immunity, Innate , Interferon Type I/genetics , Interferon Type I/metabolism , Lung/pathology , Lung/virology , Mice , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/metabolism , SARS-CoV-2 , STAT2 Transcription Factor/genetics , Virus Replication