News – A study reveals the genetic factors that may reveal or protect people with Down syndrome from SARS-CoV-2 infection, as well as the prognosis of COVID-19.
Their findings, which are published in the journal Scientific Reports, previous studies showed a tenfold mortality risk of COVID-19 for people with Down syndrome, adding further evidence to augment existing calls for priority vaccination from the vulnerable group.
The researchers analyzed all publicly available Down syndrome transcription data to determine changes that may affect disease progression and SARS-CoV-2 progression.
TMPRSS2, a gene encoding for an enzyme essential for supporting SARS-CoV-2 uptake in human cells, had 60% higher expression levels in Down syndrome. The gene is located on chromosome 21, in which people with Down syndrome have three copies.
The researchers also found higher levels of sensitivity to CXCL10, a gene that stimulates inhibition of events that cause out-of-control inflammation where the body’s immune system attacks its own lung cells. This phenomenon, known as cytokine storm, is one of the leading causes of patient hospitalization and death. The authors suggest that this may make individuals with Down syndrome more prone to a late-onset problem such as lung fibrosis.
People with Down syndrome may be susceptible to bacterial infections after COVID-19. The researchers found that trisomic cells have a trisomic expression of the NLRP3 gene, which is essential for maintaining homeostasis against pathogenic diseases.
However, the researchers also found indications that people with Down syndrome have an overactivated interferon response, an important inherited immune system that shuts down viral reproduction within cells. Two of the genes involved in interferon response – IFNAR1 and IFNAR2 – are found on chromosome 21.
One limitation of the study is that the databases studied cannot be used to assess the risk of COVID-19 across different ages. A recent study from the International Trisomy Research Society 21 reveals a significantly higher risk of mortality for people with Down syndrome over the age of 40.
Another study recently published in the History of internal treatments People with Down syndrome called COVID-19 are reported to be five times more likely to go into hospital and ten times more likely to die.
“Previous studies have shown an association between Down syndrome and higher COVID-19 mortality. These studies have not revealed a direct causal explanation but may inform policy and encourage further study,” said Dr. Mara Dierssen , Group Director at Neurobiology Cellular & Laboratory Systems at the Center for Genomic Control (CRG) and author of the study.
“Overall, we believe that people with Down syndrome who are over 40 or who have severe comorbidities are medically vulnerable, both at the stage of infection and for the prognosis once the cytokine storms begin, ”says Dr. Dierssen, who is also President of the Trisomy 21 Research Society.“ It is for this reason that people with Down syndrome should be given immediate priority for vaccination. early opposition to COVID-19 worldwide. “
According to Ilario de Toma, postdoc at CRG and co – author of the study, “we need more research to study transcription changes within lung tissue at different stages of the disease, possibly stratified by age . “
The team will further validate their findings in future studies, starting new studies using mouse models for Down syndrome that will target some of the candidates found in this study. This may provide important insights to stimulate an immune response and increase the effectiveness of vaccines with Down syndrome in the future.
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