Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19

Abstract SARS-CoV-2 infection has spread uncontrollably worldwide while it remains unknown how vulnerable populations, such as Down syndrome (DS) individuals are affected by the COVID-19 pandemic. Individuals with DS have more risk of infections with respiratory complications and present signs of au...

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Autores principales:	Ilario De Toma, Mara Dierssen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5739e8dc50634c56958b11c527a644ef
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spelling	oai:doaj.org-article:5739e8dc50634c56958b11c527a644ef2021-12-02T10:49:11ZNetwork analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-1910.1038/s41598-021-81451-w2045-2322https://doaj.org/article/5739e8dc50634c56958b11c527a644ef2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81451-whttps://doaj.org/toc/2045-2322Abstract SARS-CoV-2 infection has spread uncontrollably worldwide while it remains unknown how vulnerable populations, such as Down syndrome (DS) individuals are affected by the COVID-19 pandemic. Individuals with DS have more risk of infections with respiratory complications and present signs of auto-inflammation. They also present with multiple comorbidities that are associated with poorer COVID-19 prognosis in the general population. All this might place DS individuals at higher risk of SARS-CoV-2 infection or poorer clinical outcomes. In order to get insight into the interplay between DS genes and SARS-cov2 infection and pathogenesis we identified the genes associated with the molecular pathways involved in COVID-19 and the host proteins interacting with viral proteins from SARS-CoV-2. We then analyzed the overlaps of these genes with HSA21 genes, HSA21 interactors and other genes consistently differentially expressed in DS (using public transcriptomic datasets) and created a DS-SARS-CoV-2 network. We detected COVID-19 protective and risk factors among HSA21 genes and interactors and/or DS deregulated genes that might affect the susceptibility of individuals with DS both at the infection stage and in the progression to acute respiratory distress syndrome. Our analysis suggests that at the infection stage DS individuals might be more susceptible to infection due to triplication of TMPRSS2, that primes the viral S protein for entry in the host cells. However, as the anti-viral interferon I signaling is also upregulated in DS, this might increase the initial anti-viral response, inhibiting viral genome release, viral replication and viral assembly. In the second pro-inflammatory immunopathogenic phase of the infection, the prognosis for DS patients might worsen due to upregulation of inflammatory genes that might favor the typical cytokine storm of COVID-19. We also detected strong downregulation of the NLRP3 gene, critical for maintenance of homeostasis against pathogenic infections, possibly leading to bacterial infection complications.Ilario De TomaMara DierssenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ilario De Toma Mara Dierssen Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19
description	Abstract SARS-CoV-2 infection has spread uncontrollably worldwide while it remains unknown how vulnerable populations, such as Down syndrome (DS) individuals are affected by the COVID-19 pandemic. Individuals with DS have more risk of infections with respiratory complications and present signs of auto-inflammation. They also present with multiple comorbidities that are associated with poorer COVID-19 prognosis in the general population. All this might place DS individuals at higher risk of SARS-CoV-2 infection or poorer clinical outcomes. In order to get insight into the interplay between DS genes and SARS-cov2 infection and pathogenesis we identified the genes associated with the molecular pathways involved in COVID-19 and the host proteins interacting with viral proteins from SARS-CoV-2. We then analyzed the overlaps of these genes with HSA21 genes, HSA21 interactors and other genes consistently differentially expressed in DS (using public transcriptomic datasets) and created a DS-SARS-CoV-2 network. We detected COVID-19 protective and risk factors among HSA21 genes and interactors and/or DS deregulated genes that might affect the susceptibility of individuals with DS both at the infection stage and in the progression to acute respiratory distress syndrome. Our analysis suggests that at the infection stage DS individuals might be more susceptible to infection due to triplication of TMPRSS2, that primes the viral S protein for entry in the host cells. However, as the anti-viral interferon I signaling is also upregulated in DS, this might increase the initial anti-viral response, inhibiting viral genome release, viral replication and viral assembly. In the second pro-inflammatory immunopathogenic phase of the infection, the prognosis for DS patients might worsen due to upregulation of inflammatory genes that might favor the typical cytokine storm of COVID-19. We also detected strong downregulation of the NLRP3 gene, critical for maintenance of homeostasis against pathogenic infections, possibly leading to bacterial infection complications.
format	article
author	Ilario De Toma Mara Dierssen
author_facet	Ilario De Toma Mara Dierssen
author_sort	Ilario De Toma
title	Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19
title_short	Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19
title_full	Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19
title_fullStr	Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19
title_full_unstemmed	Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19
title_sort	network analysis of down syndrome and sars-cov-2 identifies risk and protective factors for covid-19
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5739e8dc50634c56958b11c527a644ef
work_keys_str_mv	AT ilariodetoma networkanalysisofdownsyndromeandsarscov2identifiesriskandprotectivefactorsforcovid19 AT maradierssen networkanalysisofdownsyndromeandsarscov2identifiesriskandprotectivefactorsforcovid19
_version_	1718396590530494464

Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19

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