Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning.
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 re...
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Public Library of Science (PLoS)
2023-11-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011589&type=printable |
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| author | Gavin R Meehan Vanessa Herder Jay Allan Xinyi Huang Karen Kerr Diogo Correa Mendonca Georgios Ilia Derek W Wright Kyriaki Nomikou Quan Gu Sergi Molina Arias Florian Hansmann Alexandros Hardas Charalampos Attipa Giuditta De Lorenzo Vanessa Cowton Nicole Upfold Natasha Palmalux Jonathan C Brown Wendy S Barclay Ana Da Silva Filipe Wilhelm Furnon Arvind H Patel Massimo Palmarini |
| author_facet | Gavin R Meehan Vanessa Herder Jay Allan Xinyi Huang Karen Kerr Diogo Correa Mendonca Georgios Ilia Derek W Wright Kyriaki Nomikou Quan Gu Sergi Molina Arias Florian Hansmann Alexandros Hardas Charalampos Attipa Giuditta De Lorenzo Vanessa Cowton Nicole Upfold Natasha Palmalux Jonathan C Brown Wendy S Barclay Ana Da Silva Filipe Wilhelm Furnon Arvind H Patel Massimo Palmarini |
| author_sort | Gavin R Meehan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a36ebe930d79496085f27eaa475ecb69 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2023-11-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Pathogens |
| spelling | doaj-art-a36ebe930d79496085f27eaa475ecb692025-08-20T02:31:38ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-11-011911e101158910.1371/journal.ppat.1011589Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning.Gavin R MeehanVanessa HerderJay AllanXinyi HuangKaren KerrDiogo Correa MendoncaGeorgios IliaDerek W WrightKyriaki NomikouQuan GuSergi Molina AriasFlorian HansmannAlexandros HardasCharalampos AttipaGiuditta De LorenzoVanessa CowtonNicole UpfoldNatasha PalmaluxJonathan C BrownWendy S BarclayAna Da Silva FilipeWilhelm FurnonArvind H PatelMassimo PalmariniSevere 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011589&type=printable |
| spellingShingle | Gavin R Meehan Vanessa Herder Jay Allan Xinyi Huang Karen Kerr Diogo Correa Mendonca Georgios Ilia Derek W Wright Kyriaki Nomikou Quan Gu Sergi Molina Arias Florian Hansmann Alexandros Hardas Charalampos Attipa Giuditta De Lorenzo Vanessa Cowton Nicole Upfold Natasha Palmalux Jonathan C Brown Wendy S Barclay Ana Da Silva Filipe Wilhelm Furnon Arvind H Patel Massimo Palmarini Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning. PLoS Pathogens |
| title | Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning. |
| title_full | Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning. |
| title_fullStr | Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning. |
| title_full_unstemmed | Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning. |
| title_short | Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning. |
| title_sort | phenotyping the virulence of sars cov 2 variants in hamsters by digital pathology and machine learning |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011589&type=printable |
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