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A virus-free cellular model recapitulates several features of severe COVID-19
As for all newly-emergent pathogens, SARS-CoV-2 presents with a relative paucity of clinical information and experimental models, a situation hampering both the development of new effective treatments and the prediction of future outbreaks. Here, we find that a simple virus-free model, based on publ...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410838/ https://www.ncbi.nlm.nih.gov/pubmed/34471195 http://dx.doi.org/10.1038/s41598-021-96875-7 |
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author | Lavorgna, Giovanni Cavalli, Giulio Dagna, Lorenzo Gregori, Silvia Larcher, Alessandro Landoni, Giovanni Ciceri, Fabio Montorsi, Francesco Salonia, Andrea |
author_facet | Lavorgna, Giovanni Cavalli, Giulio Dagna, Lorenzo Gregori, Silvia Larcher, Alessandro Landoni, Giovanni Ciceri, Fabio Montorsi, Francesco Salonia, Andrea |
author_sort | Lavorgna, Giovanni |
collection | PubMed |
description | As for all newly-emergent pathogens, SARS-CoV-2 presents with a relative paucity of clinical information and experimental models, a situation hampering both the development of new effective treatments and the prediction of future outbreaks. Here, we find that a simple virus-free model, based on publicly available transcriptional data from human cell lines, is surprisingly able to recapitulate several features of the clinically relevant infections. By segregating cell lines (n = 1305) from the CCLE project on the base of their sole angiotensin-converting enzyme 2 (ACE2) mRNA content, we found that overexpressing cells present with molecular features resembling those of at-risk patients, including senescence, impairment of antibody production, epigenetic regulation, DNA repair and apoptosis, neutralization of the interferon response, proneness to an overemphasized innate immune activity, hyperinflammation by IL-1, diabetes, hypercoagulation and hypogonadism. Likewise, several pathways were found to display a differential expression between sexes, with males being in the least advantageous position, thus suggesting that the model could reproduce even the sex-related disparities observed in the clinical outcome of patients with COVID-19. Overall, besides validating a new disease model, our data suggest that, in patients with severe COVID-19, a baseline ground could be already present and, as a consequence, the viral infection might simply exacerbate a variety of latent (or inherent) pre-existing conditions, representing therefore a tipping point at which they become clinically significant. |
format | Online Article Text |
id | pubmed-8410838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84108382021-09-03 A virus-free cellular model recapitulates several features of severe COVID-19 Lavorgna, Giovanni Cavalli, Giulio Dagna, Lorenzo Gregori, Silvia Larcher, Alessandro Landoni, Giovanni Ciceri, Fabio Montorsi, Francesco Salonia, Andrea Sci Rep Article As for all newly-emergent pathogens, SARS-CoV-2 presents with a relative paucity of clinical information and experimental models, a situation hampering both the development of new effective treatments and the prediction of future outbreaks. Here, we find that a simple virus-free model, based on publicly available transcriptional data from human cell lines, is surprisingly able to recapitulate several features of the clinically relevant infections. By segregating cell lines (n = 1305) from the CCLE project on the base of their sole angiotensin-converting enzyme 2 (ACE2) mRNA content, we found that overexpressing cells present with molecular features resembling those of at-risk patients, including senescence, impairment of antibody production, epigenetic regulation, DNA repair and apoptosis, neutralization of the interferon response, proneness to an overemphasized innate immune activity, hyperinflammation by IL-1, diabetes, hypercoagulation and hypogonadism. Likewise, several pathways were found to display a differential expression between sexes, with males being in the least advantageous position, thus suggesting that the model could reproduce even the sex-related disparities observed in the clinical outcome of patients with COVID-19. Overall, besides validating a new disease model, our data suggest that, in patients with severe COVID-19, a baseline ground could be already present and, as a consequence, the viral infection might simply exacerbate a variety of latent (or inherent) pre-existing conditions, representing therefore a tipping point at which they become clinically significant. Nature Publishing Group UK 2021-09-01 /pmc/articles/PMC8410838/ /pubmed/34471195 http://dx.doi.org/10.1038/s41598-021-96875-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Lavorgna, Giovanni Cavalli, Giulio Dagna, Lorenzo Gregori, Silvia Larcher, Alessandro Landoni, Giovanni Ciceri, Fabio Montorsi, Francesco Salonia, Andrea A virus-free cellular model recapitulates several features of severe COVID-19 |
title | A virus-free cellular model recapitulates several features of severe COVID-19 |
title_full | A virus-free cellular model recapitulates several features of severe COVID-19 |
title_fullStr | A virus-free cellular model recapitulates several features of severe COVID-19 |
title_full_unstemmed | A virus-free cellular model recapitulates several features of severe COVID-19 |
title_short | A virus-free cellular model recapitulates several features of severe COVID-19 |
title_sort | virus-free cellular model recapitulates several features of severe covid-19 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410838/ https://www.ncbi.nlm.nih.gov/pubmed/34471195 http://dx.doi.org/10.1038/s41598-021-96875-7 |
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