Differences in clinical presentation, severity, and treatment of COVID-19 among individuals with Down syndrome from India and high-income countries: Data from the Trisomy 21 Research Society survey.

Background: People with Down syndrome (DS) are one of the highest risk groups for mortality associated with COVID-19, but outcomes may differ across countries due to different co-morbidity profiles, exposures, and societal practices, which could have implications for disease management. This study is designed to identify differences in clinical presentation, severity, and treatment of COVID-19 between India and several high-income countries (HICs). Methods: We used data from an international survey to examine the differences in disease manifestation and management for COVID-19 patients with DS from India vs HIC. De-identified survey data collected from April 2020 to August 2021 were analysed. Results: COVID-19 patients with DS from India were on average nine years younger than those from HICs. Comorbidities associated with a higher risk for severe COVID-19 were more frequent among the patients from India than from HICs. Hospitalizations were more frequent among patients from India as were COVID-19-related medical complications. Treatment strategies differed between India and HICs, with more frequent use of antibiotics in India. The average severity score of 3.31 was recorded for Indian DS in contrast to 2.3 for European and 2.04 for US cases. Conclusions: Presentation and outcomes of COVID-19 among individuals with DS were more severe for patients from India than for those from HIC. Global efforts should especially target vaccination campaigns and other risk-reducing interventions for individuals with DS from low-income countries.

COVID-19 Vaccination of Individuals with Down Syndrome-Data from the Trisomy 21 Research Society Survey on Safety, Efficacy, and Factors Associated with the Decision to Be Vaccinated.

Individuals with Down syndrome (DS) are among the groups with the highest risk for severe COVID-19. Better understanding of the efficacy and risks of COVID-19 vaccines for individuals with DS may help improve uptake of vaccination. The T21RS COVID-19 Initiative launched an international survey to obtain information on safety and efficacy of COVID-19 vaccines for individuals with DS. De-identified survey data collected between March and December 2021 were analyzed. Of 2172 individuals with DS, 1973 (91%) had received at least one vaccine dose (57% BNT162b2), 107 (5%) were unvaccinated by choice, and 92 (4%) were unvaccinated for other reasons. Most participants had either no side effects (54%) or mild ones such as pain at the injection site (29%), fatigue (12%), and fever (7%). Severe side effects occurred in <0.5% of participants. About 1% of the vaccinated individuals with DS contracted COVID-19 after vaccination, and all recovered. Individuals with DS who were unvaccinated by choice were more likely to be younger, previously recovered from COVID-19, and also unvaccinated against other recommended vaccines. COVID-19 vaccines have been shown to be safe for individuals with DS and effective in terms of resulting in minimal breakthrough infections and milder disease outcomes among fully vaccinated individuals with DS.

Ableism at the Bedside: People with Intellectual Disabilities and COVID-19.

People with intellectual and developmental disabilities have a higher risk of mortality from COVID-19 than the general population. Providers may assume that this is due to the burden of comorbidities for this population; however, the disparity in mortality persists even when controlling for comorbidities. We review the current policies and practices that may be contributing to this higher level of mortality. We contend that pervasive ableism among medical providers leads to a variation in the medical care options that are provided to people with intellectual disabilities and their families. Due to this bias, poor outcomes for people with intellectual disabilities may become a self-fulfilling prophecy. We make recommendations to address the modifiable factors that are contributing to the higher level of mortality for people with intellectual disabilities who are infected with COVID-19, provide strategies to combat ableism within the medical field, and discuss the unique role of the primary care physician as an advocate.

COVID-19 in Children with Down Syndrome: Data from the Trisomy 21 Research Society Survey.

Adults with Down Syndrome (DS) are at higher risk for severe outcomes of coronavirus disease 2019 (COVID-19) than the general population, but evidence is required to understand the risks for children with DS, which is necessary to inform COVID-19 shielding advice and vaccination priorities. We aimed to determine the epidemiological and clinical characteristics of COVID-19 in children with DS. Using data from an international survey obtained from a range of countries and control data from the United States, we compared the prevalence of symptoms and medical complications and risk factors for severe outcomes between DS and non-DS paediatric populations with COVID-19. Hospitalised COVID-19 patients <18 years with DS had a higher incidence of respiratory symptoms, fever, and several medical complications from COVID-19 than control patients without DS <18 years. Older age, obesity, and epilepsy were significant risk factors for hospitalisation among paediatric COVID-19 patients with DS, and age and thyroid disorder were significant risk factors for acute respiratory distress syndrome. Mortality rates were low in all paediatric COVID-19 patients (with and without DS), contrasting with previous findings in adults with DS (who exhibit higher mortality than those without DS). Children with DS are at increased risk for more severe presentations of COVID-19. Efforts should be made to ensure the comprehensive and early detection of COVID-19 in this population and to identify children with DS who present comorbidities that pose a risk for a severe course of COVID-19. Our results emphasize the importance of vaccinating children with DS as soon as they become eligible.

Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer's Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study.

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer's disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid ß peptides (Aß1-40, Aß1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.

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

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.

Pneumonia and respiratory infections in Down syndrome: A scoping review of the literature.

Pneumonia and respiratory infections impact infants and children with Down syndrome; pneumonia is a leading cause of mortality in adults with Down syndrome. We aimed to review the literature to evaluate gaps and address key questions. A series of key questions were formulated a priori to inform the search strategy and review process; addressed prevalence, severity, etiology, risk factors, preventive methods, screening, and financial costs, potential benefits or harms of screening. Using the National Library of Medicine database, PubMed, detailed literature searches on pneumonia and respiratory infections in Down syndrome were performed. Previously identified review articles were also assessed. The quality of available evidence was then evaluated and knowledge gaps were identified. Forty-two relevant original articles were identified which addressed at least one key question. Study details including research design, internal validity, external validity, and relevant results are presented. Pneumonia and respiratory infections are more prevalent and more severe in individuals with Down syndrome compared to healthy controls through literature review, yet there are gaps in the literature regarding the etiology of pneumonia, the infectious organism, risk factors for infection, and to guide options for prevention and screening. There is urgent need for additional research studies in Down syndrome, especially in the time of the current COVID-19 pandemic.