COVID-19 scientific review

Immune dysregulation and susceptibility to respiratory-track infections such as COVID-19 in individuals with Down syndrome

The risk of having more severe outcomes after a respiratory tract (lung) infection is much increased in older people, especially in those with chronic medical conditions such as hypertension, diabetes, cardiovascular disease, dementia, longstanding lung disease, and cancer. The recent SARS-CoV-2 outbreak, which causes COVID-19, has proven to be particularly devastating for individuals with Down syndrome at ages above 40. As of now, the SARS-CoV-2 virus infection has been confirmed in nearly 300 million people worldwide and is responsible for more than 5 million deaths (adapted from Our World in Data).

Individuals with Down syndrome are known to have problems in the various arms of the immune response. These have been shown to be associated with increased vulnerability to lung infections caused by the influenza virus, respiratory syncytial virus, SARS-CoV-2 (COVID-19), and bacterial pneumonias. To highlight the importance of this vulnerability during the pandemic and to inform how to protect people with Down syndrome, the T21RS COVID-19 initiative has published two pivotal scientific reviews, focusing on the dysregulation of the immune response in Down syndrome and its association with the increased risk of respiratory infections and the specific susceptibility to COVID-19 in DS (Download at the end of this page).

These reviews discussed the functional dysregulation of the different branches of the immune response that occur in Down syndrome. These include changes in the innate and adaptive immune responses, their underlying genetic mechanisms, and real-life implications, such as efficacy of vaccines in Down syndrome. Moreover, these publications summarize recent findings that point at a higher risk of testing positive to SARS-Cov-2 in individuals with Down syndrome, longer and more frequent hospital admissions, and increased risk of severe COVID-19 illness and mortality than observed in the general population.

  • Testing for SARS-Cov-2 positivity in symptomatic and asymptomatic at-risk individuals may be an efficient way to reduce excess deaths and the spreading of COVID-19. Nasopharyngeal swabs and sputum are typically used to detect viral genome using RT-qPCR with a sensitivity of around 500 RNA copies. These tests can potentially be widely used in individuals with Down syndrome. Just as in the general population, priority should be given to those who have any symptom related to COVID-19, such as fever, tiredness, dry cough, shortness of breath, aches and pains, sore throat, diarrhea, nausea, runny nose, loss of smell and/or taste. However, during the initial stages of the pandemic, there have been difficulties in developing sufficient testing capacity in many countries. In addition, the false negative rate of some tests may also be an issue.
  • At T21RS, we are concerned about the potential impact of SARS-CoV-2 infection in individuals with Down syndrome. Our concern for those with Down syndrome is based on their higher likelihood for having lung  infections and immune complications, including increased rates of periodontal disease, infectious, and autoimmune disease. The extent of immune dysregulation in Down syndrome can be substantial, including functional differences in a variety of immune cells (i.e., T- and B-cells, monocytes and neutrophils) that are important for both the immune response to infection, and could mean that people with Down syndrome have a weaker antibody responses to vaccination.

Scientific Reviews

List of authors

  • Tomer Illouz, Bar-Ilan University, Israel
  • Arya Biragyn, Laboratory of Molecular Biology and Immunology, NIA, NIH
  • Orly Weissberg, Bar-Ilan University, Israel
  • Alessandro Gorohovski, Bar-Ilan University, Israel
  • Milana Frenkel-Morgenstern, Bar-Ilan University, Israel
  • Eugene Merzon, Tel Aviv University, Israel
  • Ilan Green, Tel Aviv University, Israel
  • Florencia lulita, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  • Lisi Flores-Aguilar, McGill University, Canada
  • Maria del Mar Dierssen Sotos, Centre for Genomic Regulation (CRG), Spain
  • Ilario De Toma, Centre for Genomic Regulation (CRG), Spain
  • Hefziba Lifshitz, Bar-Ilan University, Israel
  • Ayelet Gur, Bar-Ilan University, Israel
  • Sigal Eden, Bar-Ilan University, Israel
  • Stylianos antonarakis, University of Geneva, Switzerland
  • Eugene Yu, Roswell Park Comprehensive Cancer Center, USA
  • Yann Herault, Institut de Génétique Biologie Moléculaire et Cellulaire, IGBMC, France
  • Marie-Claude Potier, Paris Brain Institute (ICM), France
  • Alexandra Botté, Paris Brain Institute (ICM), France
  • Randall Roper, University Indianapolis Benjamin Sredni, USA
  • Benjamin Sredni, Bar-Ilan University, Israel
  • Ronit Sarid, Bar-Ilan University, Israel
  • Jacqueline London, Université de Paris, France
  • William Mobley, University of California, San Diego, USA
  • Andre Strydom, King’s College London, UK
  • Eitan Okun, Bar-Ilan University, Israel