Risk of Severe Coronavirus Disease 2019 Disease in Individuals With Down Syndrome: A Matched Cohort Study From a Large, Integrated Health Care System

Our matched cohort study from the pre-COVID-19 vaccination period showed that COVID-19 infection risk was lower in persons with Down syndrome compared with persons without Down syndrome, but the risk of severe COVID-19 disease was higher. Background Down syndrome (DS) is associated with an increased risk of infections attributed to immune defects. Whether individuals with DS are at an increased risk of severe coronavirus disease 2019 (COVID-19) remains unclear. Methods In a matched cohort study, we evaluated the risk of COVID-19 infection and severe COVID-19 disease in individuals with DS and their matched counterparts in a pre-COVID-19 vaccination period at Kaiser Permanente Southern California. Multivariable Cox proportion hazard regression was used to investigate associations between DS and risk of COVID-19 infection and severe COVID-19 disease. Results Our cohort included 2541 individuals with DS and 10 164 without DS matched on age, sex, and race/ethnicity (51.6% female, 53.3% Hispanic, median age 25 years [interquartile range, 14-38]). Although the rate of COVID-19 infection in individuals with DS was 32% lower than their matched counterparts (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], .56-.83), the rate of severe COVID-19 disease was 6-fold higher (aHR, 6.14; 95% CI, 1.87-20.16). Conclusions Although the risk of COVID-19 infection is lower, the risk of severe disease is higher in individuals with DS compared with their matched counterparts. Better infection monitoring, early treatment, and promotion of vaccine for COVID-19 are warranted for DS populations.