key: cord-0779522-eom5h6mh
authors: Clift, Ashley Kieran; Coupland, Carol A.C.; Keogh, Ruth H.; Hemingway, Harry; Hippisley-Cox, Julia
title: COVID-19 Mortality Risk in Down Syndrome: Results From a Cohort Study Of 8 Million Adults
date: 2020-10-21
journal: Ann Intern Med
DOI: 10.7326/m20-4986
sha: 72a63066c59f4b0913fc5f4a09734d34a4cc4e65
doc_id: 779522
cord_uid: eom5h6mh

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Adjusted for age and sex, the HR for COVID-19 -related death in adults with versus without Down syndrome was 24.94 (95% CI, 17.08 to 36.44). After adjustment for age, sex, ethnicity, BMI, dementia diagnosis, care home residency, congenital heart disease, and a range of other comorbid conditions and treatments (Table) , the HR for COVID-19 -related death was 10.39 (CI, 7.08 to 15.23); for hospitalization, it was 4.94 (CI, 3.63 to 6.73) (Figure) . There was no evidence of interactions between Down syndrome and age, sex, or BMI. The HR for death was not affected by further adjustment for smoking status and alcohol intake (HR, 10.12 [CI, 6.90 to 14.84]). For those with learning disabilities other than Down syndrome, the adjusted HR for COVID-19 -related death was 1.27 (CI, 1.16 to 1.40).

Discussion: We estimated a 4-fold increased risk for COVID-19 -related hospitalization and a 10-fold increased risk for COVID-19 -related death in persons with Down syndrome, a group that is currently not strategically protected. This was ‡ Persons on the shielded list were advised to follow strict self-isolation measures to reduce exposure to COVID-19 and were eligible for a support package that included food parcel and medicine deliveries. For the Down syndrome group, 8.07% were on the nationally maintained list of patients who were advised to shield, which will be because of a combination of small proportions of persons with Down syndrome having recorded diagnoses of conditions conferring "clinical vulnerability" and nonrecognition of Down syndrome as a risk factor for adverse outcomes.

Adjusted HR (95% CI) for the association between Down syndrome and death from COVID-19. after adjustment for cardiovascular and pulmonary diseases and care home residence, which our results suggest explained some but not all of the increased risk. These estimated adjusted associations do not have a direct causal interpretation because some adjusted variables may lie on causal pathways, but they can inform policy and motivate further investigation. Participation in day care programs or immunologic deficits could be implicated, for example. Down syndrome is the most common genetic cause of intellectual disability, with multiorgan manifestations (3). Predisposition to pneumonias and acute respiratory distress syndrome in children, airway anomalies, pulmonary hypoplasia, and inhibited pulmonary angiogenesis have been reported (4, 5) .

We are unaware of the effects of Down syndrome on COVID-19 outcomes being reported elsewhere yet during this pandemic. Novel evidence that specific conditions may confer elevated risk should be used by public health organizations, policymakers, and health care workers to strategically protect vulnerable individuals.

Development of a COVID-19 risk prediction model. Nuffield Department of Primary Care Health Sciences. 2020. Accessed at www

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