Background: Individuals with Down syndrome are an at-risk population for severe COVID-19 outcomes, due to genetic predispositions and comorbidities. The current study focused on differences between persons with and without Down syndrome regarding age and severity of disease. Method: We used medical statistics to compare patients with and without Down syndrome who were admitted to Swiss hospitals (2020 and 2022) with a COVID-19 diagnosis. Differences in age, hospitalisation characteristics, mortality, and additional diagnoses were investigated. Results: Results revealed a lower median age and greater risk of intensive care unit admission and mortality among patients with Down syndrome. No differences were found in length of hospital stay. Conclusions: There is some evidence of increased vulnerability in people with Down syndrome compared to other patients, particularly in terms of mortality rates. However, compared to studies from other countries, the situation of people with Down syndrome does not appear to be particularly critical.