A virus-free cellular model recapitulates several features of severe COVID-19
Abstract 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, base...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-96875-7 |
| _version_ | 1818683786556080128 |
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| author | Giovanni Lavorgna Giulio Cavalli Lorenzo Dagna Silvia Gregori Alessandro Larcher Giovanni Landoni Fabio Ciceri Francesco Montorsi Andrea Salonia |
| author_facet | Giovanni Lavorgna Giulio Cavalli Lorenzo Dagna Silvia Gregori Alessandro Larcher Giovanni Landoni Fabio Ciceri Francesco Montorsi Andrea Salonia |
| author_sort | Giovanni Lavorgna |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-17T10:40:16Z |
| format | Article |
| id | doaj.art-c7ea18b3b3a340c1a5a5c94cae73ab75 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T10:40:16Z |
| publishDate | 2021-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c7ea18b3b3a340c1a5a5c94cae73ab752022-12-21T21:52:17ZengNature PortfolioScientific Reports2045-23222021-09-0111111310.1038/s41598-021-96875-7A virus-free cellular model recapitulates several features of severe COVID-19Giovanni Lavorgna0Giulio Cavalli1Lorenzo Dagna2Silvia Gregori3Alessandro Larcher4Giovanni Landoni5Fabio Ciceri6Francesco Montorsi7Andrea Salonia8Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San RaffaeleUniversity Vita-Salute San RaffaeleUniversity Vita-Salute San RaffaeleSan Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San RaffaeleDivision of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San RaffaeleUniversity Vita-Salute San RaffaeleUniversity Vita-Salute San RaffaeleDivision of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San RaffaeleDivision of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San RaffaeleAbstract 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.https://doi.org/10.1038/s41598-021-96875-7 |
| spellingShingle | Giovanni Lavorgna Giulio Cavalli Lorenzo Dagna Silvia Gregori Alessandro Larcher Giovanni Landoni Fabio Ciceri Francesco Montorsi Andrea Salonia A virus-free cellular model recapitulates several features of severe COVID-19 Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-021-96875-7 |
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