This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Mara Dierssen
Center for Genomic Regulation
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0853-6865
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: SARS-CoV-2 has spread uncontrollably worldwide while we still ignore how particularly 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 suffer from 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.
Methods: In order to get insight into the interplay between DS genes and SARS-cov2 infection and pathogenesis we retrieved the genes belonging to the molecular pathways involved in COVID-19 and the host proteins interacting with viral proteins from SARS-CoV-2. We therefore analyzed the overlaps of these genes with HSA21 genes, HSA21 interactors and other genes consistently differentially expressed in DS (using public transcriptomic datasets) creating a DS-SARS-CoV-2 network.
Results: We detected COVID-19 protective and risk factors that might affect the susceptibility of individuals with DS both at the infection stage and in the progression to acute respiratory distress syndrome.
Conclusion: 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, even though the anti-viral interferon I signaling is upregulated in DS and this might increase the initial anti-viral response. 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.
Keywords
Down syndrome, COVID-19, SARS-CoV-2, coronavirus, interferon, TMPRSS2, network analysis, transcriptomics, meta-analysis, trisomy 21
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Mara Dierssen
Center for Genomic Regulation
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0853-6865
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 12 Jun, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: SARS-CoV-2 has spread uncontrollably worldwide while we still ignore how particularly 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 suffer from 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.
Methods: In order to get insight into the interplay between DS genes and SARS-cov2 infection and pathogenesis we retrieved the genes belonging to the molecular pathways involved in COVID-19 and the host proteins interacting with viral proteins from SARS-CoV-2. We therefore analyzed the overlaps of these genes with HSA21 genes, HSA21 interactors and other genes consistently differentially expressed in DS (using public transcriptomic datasets) creating a DS-SARS-CoV-2 network.
Results: We detected COVID-19 protective and risk factors that might affect the susceptibility of individuals with DS both at the infection stage and in the progression to acute respiratory distress syndrome.
Conclusion: 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, even though the anti-viral interferon I signaling is upregulated in DS and this might increase the initial anti-viral response. 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.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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