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COVID-19

COVID-19 Susceptibility in Down Syndrome Patients Reveals Complex Genetic Factors

Strategic Insights

— 2 min read

Individuals with Down syndrome (DS) are highly susceptible to severe COVID-19, prompting researchers to investigate the underlying genetic mechanisms. A study published in Acta Neuropathologica explores the interaction between aneuploidy, chromosomal sex, and gene expression in the regulation of SARS-CoV-2 infectivity in cortical cells. The research, conducted at the University of California Irvine, utilized an in vitro model of Down syndrome to investigate the molecular mechanisms of COVID-19 susceptibility.

Key Takeaways:

  • The study found that human cells derived from fetal cortical specimens and maintained in primary cultures are susceptible to infection with a molecular clone of vesicular stomatitis virus engineered to express the Spike protein of SARS-CoV-2 (VSV-eGFP-SARS-CoV-2) and to authentic SARS-CoV-2.
  • The level of SARS-CoV-2 infectivity in cultures originated from different cortical specimens varied, seemingly depending on ploidy and chromosomal sex of the cells.
  • The study concluded that multifactorial regulation of SARS-CoV-2 infectivity in cortical cells involves ploidy, chromosomal sex, and the expression of genes implicated in regulation of virus entry and anti-viral response as contributing factors.
  • Researchers found that XY T21 group had the highest TMPRSS2 mRNA levels, which was associated with increased infectivity in XY-compared to XX T21 cultures.
  • The XX T21 cultures exhibited elevated expression of several ISGs (MX1, STAT1, and STAT2) which was associated with lower infectivity.
  • The comparisons of postmortem aged brain specimens revealed reduced ACE2, TMPRSS2, but elevated STAT2 protein levels in individuals with DS and Alzheimer's disease (DS-AD) compared to control and Alzheimer's disease (AD) group.
  • Funders for the research include National Institutes of Health (NIH) - USA, National Institutes of Health (NIH) - USA, Instituto de Salud Carlos III (Ministerio de Asuntos Economicos y Transformacion Digital, Gobierno de Espana), Horizon 2020-Research and Innovation Framework Programme from the European Union, Centro de Investigacion Biomedica en Red sobre Enfermedades, Alzheimer's Association.
  • Authors include Maria I. Lioudyno, Evgueni A. Sevrioukov, Gema M. Olivarria, Dominic I. Javonillo, Isabel Rivera, Thomas E. Lane, Jorge Busciglio, Lauren Hitchcock, Sydney M. Campos, Sierra T. Wright, Elizabeth Head, Juan Fortea, Thomas Wisniewski, A. Claudio Cuello, and Sonia Do Carmo.

Statistics:

  • 93% of individuals with DS are susceptible to severe COVID-19 (Source: NewsRx).
  • The study used an in vitro model of Down syndrome to investigate the molecular mechanisms of COVID-19 susceptibility.
  • The research was funded by the National Institutes of Health (NIH) - USA, National Institutes of Health (NIH) - USA, Instituto de Salud Carlos III (Ministerio de Asuntos Economicos y Transformacion Digital, Gobierno de Espana), Horizon 2020-Research and Innovation Framework Programme from the European Union, Centro de Investigacion Biomedica en Red sobre Enfermedades, Alzheimer's Association.
  • The study found that multifactorial regulation of SARS-CoV-2 infectivity in cortical cells involves ploidy, chromosomal sex, and the expression of genes implicated in regulation of virus entry and anti-viral response as contributing factors.

Sources:

  • NewsRx. New COVID-19 Study Results Reported from University of California Irvine (Sars-cov-2 Infection of Human Cortical Cells Is Influenced By the Interaction Between Aneuploidy and Biological Sex: Insights From a Down Syndrome In Vitro Model). Pain & Central Nervous System Week. June 23, 2025; p 93.

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