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

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• dc.contributor.author De Toma, Ilario
• dc.contributor.author Dierssen, Mara
• dc.date.accessioned 2021-03-24T09:12:15Z
• dc.date.available 2021-03-24T09:12:15Z
• dc.date.issued 2021
• dc.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.
• dc.description.sponsorship Funding: the lab of MD is supported by the CRG Severo Ochoa excellence grant (SEV-2016-0571); the CIBER of Rare Diseases; and Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (Grups consolidats 2017 SGR 926). We also acknowledge the support of the Spanish Ministry of Science and Innovation and Universities (MSIU) to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme/Generalitat de Catalunya
• dc.format.mimetype application/pdf
• dc.identifier.citation Toma ID, Dierssen M. Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19. Sci Rep. 2021 Jan 21;11(1):1930. DOI: 10.1038/s41598-021-81451-w
• dc.identifier.doi http://dx.doi.org/10.1038/s41598-021-81451-w
• dc.identifier.issn 2045-2322
• dc.identifier.uri http://hdl.handle.net/10230/46922
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Scientific Reports. 2021 Jan 21;11(1):1930
• dc.rights © Ilario De Toma & Mara Dierssen 2021. 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
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.other Down, Síndrome de
• dc.subject.other COVID-19 (Malaltia)
• dc.title Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion