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.
Highlights
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
To get insight into the interplay between genes consistently deregulated in DS and SARS-cov[2] infection and pathogenesis we built a DS-SARS-CoV-2 network
Half of the nodes in the DS-SARS-CoV-2 network (55/114 nodes) contained proteins involved in host Covid-19 related pathways, while the other half (59/114 nodes) contained host proteins known to interact with viral proteins
Summary
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 develop more severe complications during other viral respiratory infections such as influenza[2] and respiratory syncytial virus (RSV)[3], including pneumonia, hospitalization, intubation and greater mortality due to secondary bacterial infections Another risk factor is that immune response is substantially impaired in DS4. We reasoned that the levels of proteins interacting with or regulated by HSA21 genes (HSA21 interactors) are more likely to be deregulated in cases of trisomy 21 We analyzed their overlap with molecular pathways involved in COVID-19 and the host proteins interacting with viral proteins from SARS-CoV-2 and created a DS-SARS-CoV-2 network
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