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...

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Autores principales:	Giovanni Lavorgna, Giulio Cavalli, Lorenzo Dagna, Silvia Gregori, Alessandro Larcher, Giovanni Landoni, Fabio Ciceri, Francesco Montorsi, Andrea Salonia
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c7ea18b3b3a340c1a5a5c94cae73ab75
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spelling	oai:doaj.org-article:c7ea18b3b3a340c1a5a5c94cae73ab752021-12-02T15:28:57ZA virus-free cellular model recapitulates several features of severe COVID-1910.1038/s41598-021-96875-72045-2322https://doaj.org/article/c7ea18b3b3a340c1a5a5c94cae73ab752021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96875-7https://doaj.org/toc/2045-2322Abstract 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.Giovanni LavorgnaGiulio CavalliLorenzo DagnaSilvia GregoriAlessandro LarcherGiovanni LandoniFabio CiceriFrancesco MontorsiAndrea SaloniaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	virus-free cellular model recapitulates several features of severe covid-19
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c7ea18b3b3a340c1a5a5c94cae73ab75
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A virus-free cellular model recapitulates several features of severe COVID-19

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