question: Background: Down Syndrome (DS) is one of the most impacted population to the COVID-19 pandemic.Methods: The markers for demographic profile, clinical symptoms, comorbidities, and the clinical of severe acute respiratory syndrome (SARS)evolution of first year of COVID-19 pandemic in Brazil was obtained from a Brazilian open-access database. The data were compared between (i) individuals with DS and positive for COVID-19 [G1;1,619 (0.4%)] and individuals with SARS due to other etiologic agents [G2;1,431 (0.4%)];(ii) G1 individuals versus individuals with COVID-19, but without DS or comorbidities [G3;222,181 (64.8%)].Findings: Individuals from G1 when compared to G2 were older (≥25 yo), presented more symptoms related to severe illness and comorbidities, needed more frequently intensive care unit (ICU) treatment as well as noninvasive mechanical ventilation (MV), and presented a nearly 3-fold-increased risk for mortality. Individuals from G1 when compared to G3 were younger (<24 yo), more prone to nosocomial infection, presented increased chance for symptoms related to a more severe illness;needed frequently hospitalization, ICU treatment, or invasive and noninvasive MV, presented almost a 4-fold-increased risk for mortality. Also, the high mortality rate in G1 was associated with oldest age (≥25 yo), presence of symptoms and sign related to a more severe clinical condition or obesity. The need for hospitalization in G1 was associated to a low mortality rate. On the other hand, individuals who needed ICU treatment and MV presented high mortality rate.Interpretation: Individuals with DS are most affected by COVID-19 and demonstrated particularities regarding comorbidities, clinical signs and symptoms, needed MV regularly, and high mortality rate.Funding: MNB received a grant from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo – Acronym for São Paulo Research Foundation;#2021/05810-7).Declaration of Interest: None to declare.