COVID-19 Hospitalization is More Frequent and Severe in Down Syndrome and Affects Patients a Decade Younger.

Background Individuals with rare disorders, like Down syndrome (DS) are historically understudied. Currently, it is not known how COVID-19 pandemic affects individuals with DS. Herein, we report an analysis of individuals with DS who were hospitalized with COVID-19 in the Mount Sinai Health System in New York City, USA. Methods In this retrospective, single-center study of 4,615 patients hospitalized with COVID-19, we analyzed all patients with DS admitted in the Mount Sinai Health System. Hospitalization rates, clinical and outcomes were assessed. Findings Contrary to an expected number of one, we identified six patients with DS. We found that patients with DS are at an 8.9-fold higher risk of hospitalization with COVID-19 when compared to non-DS patients. Hospitalized DS individuals are on average 10 years younger than non-DS patients with COVID-19. Moreover, type 2 diabetes mellitus appears to be an important driver of this susceptibility to COVID-19. Finally, patients with DS have more severe outcomes than controls, and are more likely to progress to sepsis in particular. Interpretation We demonstrate that individuals with DS represent a higher risk population for COVID-19 compared to the general population and conclude that particular care should be taken for both the prevention and treatment of COVID-19 in these patients. Funding National Institute of Allergy and Infectious Diseases. Evidence before this study We searched PubMed and Google Scholar on May 26, 2020, for articles describing the features of patients in Down syndrome infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the search terms “SARS-CoV-2” or “COVID-19” and “Down syndrome” or “Trisomy 21.” We found only one case report describing a cluster of 4 cases of COVID-19 in a healthcare facility for patients with mental retardation. Added value of this study We compared the hospitalization rates of DS patients to over 4,500 individuals without DS, and we assessed comorbidities and outcomes of individuals with DS compared to age, race, and sex-matched controls hospitalized with COVID-19. To the best of our knowledge, we provide the first evidence that patients with DS with are at higher risk of hospitalization with COVID-19 and more severe disease progression than non-DS patients. Implications of all the available evidence We demonstrate that individuals with DS are a high-risk population for COVID-19 and suggest appropriate measures should be taken for both the prevention and treatment of COVID-19 in these patients. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement NIAID R01 0255 C811 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: HS#: 18-00627 GCO#1: 16-0275(0002) Icahn School of Medicine at Mount Sinai GCO#2: 19-0581(0001) National Institutes of Health All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The authors confirm that the data supporting the findings of this study are available within the article or its supplementary materials.