Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning Article Swipe
Gavin R. Meehan
,
Vanessa Herder
,
Jay Allan
,
Xinyi Huang
,
Karen Kerr
,
Diogo Corrêa Mendonça
,
Georgios Ilia
,
Derek Wright
,
Kyriaki Nomikou
,
Quan Gu
,
Sergi Molina Arias
,
Florian Hansmann
,
Alexandros Hardas
,
Charalampos Attipa
,
Giuditta De Lorenzo
,
Vanessa M. Cowton
,
Nicole Upfold
,
Natasha Palmalux
,
Jonathan C. Brown
,
William Barclay
,
Ana da Silva Filipe
,
Wilhelm Furnon
,
Arvind H. Patel
,
Massimo Palmarini
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1371/journal.ppat.1011589
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1371/journal.ppat.1011589
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.
Related Topics
Concepts
Virulence
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Coronavirus disease 2019 (COVID-19)
Virology
2019-20 coronavirus outbreak
Digital pathology
Biology
Computational biology
Medicine
Pathology
Genetics
Infectious disease (medical specialty)
Disease
Gene
Outbreak
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.ppat.1011589
- OA Status
- gold
- Cited By
- 14
- References
- 70
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4388451568
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4388451568Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1371/journal.ppat.1011589Digital Object Identifier
- Title
-
Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learningWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-11-07Full publication date if available
- Authors
-
Gavin R. Meehan, Vanessa Herder, Jay Allan, Xinyi Huang, Karen Kerr, Diogo Corrêa Mendonça, Georgios Ilia, Derek Wright, Kyriaki Nomikou, Quan Gu, Sergi Molina Arias, Florian Hansmann, Alexandros Hardas, Charalampos Attipa, Giuditta De Lorenzo, Vanessa M. Cowton, Nicole Upfold, Natasha Palmalux, Jonathan C. Brown, William Barclay, Ana da Silva Filipe, Wilhelm Furnon, Arvind H. Patel, Massimo PalmariniList of authors in order
- Landing page
-
https://doi.org/10.1371/journal.ppat.1011589Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1371/journal.ppat.1011589Direct OA link when available
- Concepts
-
Virulence, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Coronavirus disease 2019 (COVID-19), Virology, 2019-20 coronavirus outbreak, Digital pathology, Biology, Computational biology, Medicine, Pathology, Genetics, Infectious disease (medical specialty), Disease, Gene, OutbreakTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
14Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 5, 2024: 8, 2023: 1Per-year citation counts (last 5 years)
- References (count)
-
70Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| corresponding_author_ids | https://openalex.org/A5088242299, https://openalex.org/A5054763169, https://openalex.org/A5060555512, https://openalex.org/A5055039109, https://openalex.org/A5045414798, https://openalex.org/A5108922457, https://openalex.org/A5053416521, https://openalex.org/A5023605284, https://openalex.org/A5065310780, https://openalex.org/A5015454385, https://openalex.org/A5053053781, https://openalex.org/A5101503199, https://openalex.org/A5033093938, https://openalex.org/A5092133885, https://openalex.org/A5027473390, https://openalex.org/A5030451410, https://openalex.org/A5037075762, https://openalex.org/A5030782374, https://openalex.org/A5038353299, https://openalex.org/A5078811003, https://openalex.org/A5067177545, https://openalex.org/A5043030283, https://openalex.org/A5087878254, https://openalex.org/A5025801962 |
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| corresponding_institution_ids | https://openalex.org/I133836048, https://openalex.org/I4210146449, https://openalex.org/I47508984, https://openalex.org/I926574661, https://openalex.org/I98677209 |
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