Meehan, G. R. et al. (2023) Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning. PLoS Pathogens, 19(11), e1011589. (doi: 10.1371/journal.ppat.1011589) (PMID:37934791) (PMCID:PMC10656012)
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Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to evolve throughout the coronavirus disease-19 (COVID-19) pandemic, giving rise to multiple variants of concern (VOCs) with different biological properties. As the pandemic progresses, it will be essential to test in near real time the potential of any new emerging variant to cause severe disease. BA.1 (Omicron) was shown to be attenuated compared to the previous VOCs like Delta, but it is possible that newly emerging variants may regain a virulent phenotype. Hamsters have been proven to be an exceedingly good model for SARS-CoV-2 pathogenesis. Here, we aimed to develop robust quantitative pipelines to assess the virulence of SARS-CoV-2 variants in hamsters. We used various approaches including RNAseq, RNA in situ hybridization, immunohistochemistry, and digital pathology, including software assisted whole section imaging and downstream automatic analyses enhanced by machine learning, to develop methods to assess and quantify virus-induced pulmonary lesions in an unbiased manner. Initially, we used Delta and Omicron to develop our experimental pipelines. We then assessed the virulence of recent Omicron sub-lineages including BA.5, XBB, BQ.1.18, BA.2, BA.2.75 and EG.5.1. We show that in experimentally infected hamsters, accurate quantification of alveolar epithelial hyperplasia and macrophage infiltrates represent robust markers for assessing the extent of virus-induced pulmonary pathology, and hence virus virulence. In addition, using these pipelines, we could reveal how some Omicron sub-lineages (e.g., BA.2.75 and EG.5.1) have regained virulence compared to the original BA.1. Finally, to maximise the utility of the digital pathology pipelines reported in our study, we developed an online repository containing representative whole organ histopathology sections that can be visualised at variable magnifications (https://covid-atlas.cvr.gla.ac.uk). Overall, this pipeline can provide unbiased and invaluable data for rapidly assessing newly emerging variants and their potential to cause severe disease.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | De Lorenzo, Dr Giuditta and Furnon, Dr Wilhelm and Wright, Mr Derek and Kerr, Ms Karen and Ilia, Mr George and Correa Mendonca, Dr Diogo and Nomikou, Dr Kyriaki and Palmarini, Professor Massimo and Upfold, Dr Nicole and Attipa, Dr Charalampos and Palmalux, Natasha and Meehan, Dr Gavin and Herder, Dr Vanessa and Gu, Dr Quan and Cowton, Dr Vanessa and Da Silva Filipe, Dr Ana and Patel, Professor Arvind and Huang, Ms Xinyi and Allan, Mr Jay and Molina Arias, Mr Sergi |
Creator Roles: | Meehan, G.Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data curation, Writing – original draft, Visualization, Supervision, Project administration Herder, V.Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data curation, Writing – original draft, Visualization, Supervision, Project administration Allan, J.Methodology, Formal analysis, Investigation Huang, X.Formal analysis, Investigation Kerr, K.Investigation Correa Mendonca, D.Investigation Ilia, G.Methodology, Formal analysis, Investigation Wright, D.Validation Nomikou, K.Methodology, Formal analysis, Investigation Gu, Q.Methodology, Software, Formal analysis, Investigation, Data curation Molina Arias, S.Investigation Attipa, C.Formal analysis De Lorenzo, G.Resources Cowton, V.Resources Upfold, N.Formal analysis, Investigation Palmalux, N.Methodology, Formal analysis, Investigation, Data curation Da Silva Filipe, A.Methodology, Supervision Furnon, W.Methodology, Formal analysis Patel, A.Conceptualization, Writing – original draft, Supervision, Project administration, Funding acquisition Palmarini, M.Conceptualization, Writing – review and editing, Visualization, Supervision, Project administration, Funding acquisition |
Authors: | Meehan, G. R., Herder, V., Allan, J., Huang, X., Kerr, K., Correa Mendonca, D., Ilia, G., Wright, D. W., Nomikou, K., Gu, Q., Molina Arias, S., Hansmann, F., Hardas, A., Attipa, C., De Lorenzo, G., Cowton, V., Upfold, N., Palmalux, N., Brown, J. C., Barclay, W. S., Da Silva Filipe, A., Furnon, W., Patel, A. H., and Palmarini, M. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
Journal Name: | PLoS Pathogens |
Publisher: | Public Library of Science |
ISSN: | 1553-7366 |
ISSN (Online): | 1553-7374 |
Copyright Holders: | Copyright: © 2023 Meehan et al. |
First Published: | First published in PLoS Pathogens 19(11): e1011589 |
Publisher Policy: | Reproduced under a Creative Commons licence |
Data DOI: | 10.5525/gla.researchdata.1513 |
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