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: Collectively, 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 and exposures, which could have implications for disease management. The present study is designed to identify differences in clinical presentation, severity, and treatment of COVID-19 between India and a set of high-income countries (HIC).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 versus HIC. De-identified survey data collected from April 2020 to August 2021, were analyzed.Findings: COVID-19 patients with DS from India were on average nine years younger than those from HIC. Comorbidities associated with higher risk for severe COVID-19 were more frequent among the patients from India than from HIC. Hospitalizations were more frequent among patients from India as were COVID-related medical complications. Treatment strategies differed between India and HIC, with more frequent use of antibiotic in India. Average severity score was recorded 3.31 for Indian DS in contrast to 2.3 for European and 2.04 for US cases.Interpretation: 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 to individuals with DS from low-income countries.Funding Information: PH is supported by University Grant Commission, India (UGC/21/06/2015 (i)EU-V). SG is supported by Government of West Bengal (DST, WB) Grant no. SG/WBDST/S&T 1000114/2016 and UGC-UPEII, DST-PURSE programs (Grant no. UGC/859/UPE-2 BIO). AH is supported by the HERCULES Center (NIEHS P30ES019776) and the LuMind IDSC Foundation. The REDCap survey and database management system at Emory University was supported by Library Information Technology Services grant support (UL1 TR000424). ACSC is supported by the Alana USA Foundation, Awakening Angels Foundation, and the Infectious Diseases Society of America (IDSA). MD is supported by the Centre for Genomic Regulation Severo Ochoa excellence grant, the CIBER of Rare Diseases, DURSI 2017SGR595, and acknowledges the Spanish Ministry of Science, Innovation and Universities (MSIU) to the EMBL partnership, the Centro de Excelencia Severo Ochoa and CERCA (GenCat). AS is supported by the MRC (MR/ S011277/1; MR/S005145/1; MR/R024901/1), Lumind IDSC, The LeJeune Foundation and the European Commission (H2020 SC1 Gene overdosage and comorbidities during the early lifetime in Down syndrome GO-DS21- 848077). ML was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at UCL Great Ormond Street Institute of Child Health/Great Ormond Street Hospital NHS Foundation Trust). DRdeA was partially supported by Spanish Fondo de Investigacion Sanitaria-Instituto Carlos III (FIS-ISCIII), grant no. PI19/00634; BAC has research support from Various Grateful Families of Patients. The Research Programme on Biomedical Informatics (GRIB) is a member of the Spanish National Bioinformatics Institute (INB), funded by ISCIII and EDER (PT17/0009/ 0014). The DCEXS is a ‘Unidad de Excelencia Marí a de Maeztu’, funded by the AEI (CEX2018-000782-M). The GRIB is also supported by the Agencia de G d ’AjutsUniversitarisi de Recerca (AGAUR), Generalitat de Catalunya (2017 SGR 00519). This study was also supported by the Fondo de InvestigacionesSanitario (FIS), Instituto de Salud Carlos III (PI18/00335 to MCI, PI14/ 01126 and PI17/01019 to JF), partly jointly funded by Fondo Europeo de Desarrollo Regional, Union Europea, Una manera de hacer Europa; the Jerome Lejeune Foundation (No.1319 Cycle 2019B to MCI); the National Institutes of Health (NIA grants 1R01AG056850 - 01A1; R21AG056974 and R01AG061566 to JF); Departament de Salut de la Generalitat de Catalunya, PlaEstrategic de RecercaiInnovaci o enSalut (SLT006/17/00119 to JF); and Fundacio La Marat o de TV3 (20141210 to JF).Declaration of Interests: We declare no competing interests.Ethics Approval Statement: Each institution that participated in this global study and disseminated the survey through families and clinicians obtained IRB/ethics approval (appendix p 2). The study was performed following the Declaration of Helsinki. All participants who completed the questionnaires provided informed consent.