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Newswise – Study reveals genetic factors that may expose or protect people with Down syndrome from infection with SARS-CoV-2, as well as the prognosis of COVID-19.
Their results, which are published in the journal Scientific reports, follow previous studies showing a tenfold risk of death from COVID-19 for people with Down syndrome, adding further evidence to strengthen existing calls for priority vaccination of the medically vulnerable group.
The researchers analyzed all publicly available Down syndrome transcriptomic data to discover alterations that could affect the infection and progression of SARS-CoV-2 disease.
TMPRSS2, a gene that codes for an enzyme essential to aid entry of SARS-CoV-2 into human cells, had 60% higher expression levels in Down syndrome. The gene is located on chromosome 21, of which people with Down syndrome have three copies.
Researchers also found higher expression levels for CXCL10, a gene that can trigger a cascade of events leading to uncontrolled inflammation where the body’s immune system attacks its own lung cells. This phenomenon, known as a cytokine storm, is one of the leading causes of hospitalization and death in patients. The authors hypothesize that this could lead people with Down syndrome to be more susceptible to late complications like pulmonary fibrosis.
People with Down syndrome may also be susceptible to subsequent bacterial infections after COVID-19. Researchers have found that cells with Down’s syndrome have lower expression of the NLRP3 gene, which is essential for maintaining homeostasis against pathogenic infections.
However, researchers have also found signs that people with Down syndrome have an overactivated response to interferon, an important innate defense that prevents viral replication in cells. Two of the genes linked to an interferon response – IFNAR1 and IFNAR2 – are found on chromosome 21.
One of the limitations of the study is that the data sets studied cannot be used to assess the risk of COVID-19 at different ages. A recent study by the International Trisomy 21 Research Society found an increased risk of death in people with Down syndrome over 40 years of age.
Another study recently published in the Annals of Internal Medicine reported that people with Down syndrome affected by COVID-19 in the UK are five times more likely to be hospitalized and ten times more likely to die.
“Previous studies have shown an association between Down syndrome and higher mortality from COVID-19. These studies have not shown a direct causal interpretation, but may inform policy and motivate further investigation, ”says Dr Mara Dierssen, group leader at Cellular & Systems Neurobiology laboratory at the Center for Genomic Regulation (CRG) and author of the study.
“Overall, we consider people with Down’s syndrome over the age of 40 or with significant comorbidities to be medically highly vulnerable, both in infection and prognosis once cytokine storms begin. Says Dr Dierssen, who is also the former president of the Trisomy 21 Research Society. “That is why people with Down syndrome should be an immediate priority for early vaccination against COVID-19 around the world.”
According to Ilario de Toma, post-doctoral fellow at CRG and co-author of the study, “we need more research to study the transcriptomic alterations in lung tissue during the different stages of infection, possibly stratified by age” .
The team will further validate their results in future studies, initiating new studies using mouse models for Down syndrome that target some of the candidates found in this study. This can provide important information for boosting the immune response and increasing the future effectiveness of vaccination for people with Down syndrome.
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