Risk of Severe COVID-19 Disease in Individuals with Down syndrome: a Matched Cohort Study from a Large, Integrated Health Care System

ABSTRACT

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 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 2,541 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]), with pulmonary disease as the most common comorbidity (13.1%) followed by diabetes (5.4%). While the rate of COVID-19 infection in individuals with DS was 32% lower than their matched counterparts (adjusted hazard ratio [aHR] 0.68, 95% CI 0.56-0.83), the rate of severe COVID-19 disease was 6-fold higher (aHR 6.14, 95% CI 1.87-20.16) (Table 1). The Kaplan-Meier plot demonstrated similar cumulative incidence for those with and without DS at the beginning of the pandemic, followed by a rate increase in July 2020 (at 4 months of follow-up), and in November 2020 (at 8 months of follow-up) (Figure 1), after which the cumulative incidence for those with DS was consistently higher. Figure 2 demonstrated consistently higher cumulative incidence estimates of COVID-19 hospitalization for those with DS than those without. (Table Presented) Conclusion. Although the risk of COVID-19 infection is lower, the risk of severe disease is higher in individuals with DS compared to their matched counterparts. Better infection monitoring, early treatment, and promotion of vaccine for COVID-19 are warranted for DS populations.