Medical vulnerability of individuals with Down syndrome to severe COVID-19–data from the Trisomy 21 Research Society and the UK ISARIC4C survey

Abstract

Background Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. Methods The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers on patients with COVID-19 and DS. Data collected between April and October 2020 (N=1046) were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS. Findings The mean age of COVID-19 patients with DS in the T21RS survey was 29 years (SD = 18). Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Joint/muscle pain and vomiting or nausea were less frequent ( p < 0.01), whereas altered consciousness/confusion were more frequent ( p < 0.01). Risk factors for hospitalization and mortality were similar to the general population with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher in patients with DS (T21RS DS versus non-DS patients: risk ratio (RR) = 3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus non-DS patients: RR = 2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality. Interpretation Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of medical complications and mortality, especially from age 40. Funding Down Syndrome Affiliates in Action, DSMIG-USA, GiGi's Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, The Matthew Foundation, NDSS, National Task Group on Intellectual Disabilities and Dementia Practices.

Immune Dysregulation and the Increased Risk of Complications and Mortality Following Respiratory Tract Infections in Adults With Down Syndrome

“…Altered consciousness or confusion were more common in hospitalized individuals with DS compared with hospitalized individuals without DS. However, joint pain, muscle aches, and vomiting/nausea were less frequent in DS (9). 60% of DS cases from the T21RS survey, reported by clinicians, developed medical complications due to COVID-19, which correlated with higher mortality rates.…”

“…The SARS-CoV-2 outbreak, which causes coronavirus disease 2019 (COVID-19), is particularly life-threatening to individuals with DS due to preexisting co-morbidities, health and housing conditions, immune dysfunction, and premature aging (9,50). A study conducted during the pandemic using multivariate logistic regression on the 'Leumit Healthcare Services' database in Israel reported a significant association between DS and the likelihood of being tested positive for SARS-CoV-2 (adjusted odds ratio 1.64).…”

“…Keywords: Down syndrome, immune dysregulation, hospitalization, respiratory tract infections, interferon, COVID-19 OVERVIEW Individuals with Down syndrome (DS) exhibit a higher risk of developing severe responses to infectious diseases compared to the general population (1)(2)(3)(4)(5)(6)(7)(8)(9). Chromosome 21 (Chr21), which is triplicated in DS, harbors several essential immune-related genes, such as four out of the six subunits of IFN receptors (10), b-2 integrin (ITGB2) (11), ubiquitin associated and SH3 domain containing A (UBASH3A) (12), autoimmune regulator (AIRE) (13), and more (Figures 1, 2).…”

“…At the individual level, the immune dysregulation observed in DS is associated with blunted response to vaccines (21,25) and increased risk of infections, more prominently in the respiratory tract (8,9). Moreover, the risk of respiratory infections may be exacerbated by unique anatomical airway features of individuals with DS (26) (Figure 1).…”

Equitable Vaccine Access within an Age-Based Framework

“…2 plots the COVID-19 mortality risk ratios from the present analysis and for published data on Down syndrome, intellectual or developmental disability, and organ transplant. Early in the pandemic, Down syndrome was reported to be associated with a 10-fold elevation in COVID-19 mortality ( 6 ), though an analysis of two more recent datasets has found elevation of 2.9- and 3.5-fold, respectively ( 7 ). Intellectual or developmental disability (a broader characteristic than Down syndrome) has been reported to be associated with an elevation in COVID-19 mortality of 5.9-( 8 ) to 7.8-fold ( 9 ).…”