We analysed data for the period January 2020 to May 2021 and the cohort comprised 43,578 patients.
Pattern of Infection Rates During the Pandemic
As Fig. 1 shows, the excess of COVID-19 diagnoses in DS individuals was more prominent during the peak periods of the pandemic in April/May 2020 and November/December 2020. The excess rates in people with DS in the second wave of the pandemic occurred despite enhanced awareness of protective measures such as wearing masks and limiting social contacts, suggesting that either these measures were not sufficient to protect this high-risk group or otherwise were not consistently applied.
Table 1 shows the demographic characteristics and comorbidities of DS cases and general population controls according to COVID-19 diagnosis. As expected, a higher proportion of people with DS were diagnosed with COVID-19 compared to controls (7.4% vs 5.6%, p ≤ 0.001).
In the DS group, people diagnosed with COVID-19 had higher rates of anxiety disorders, other chronic inflammatory conditions/other autoimmune conditions, cerebrovascular accidents, dementia, depression, diabetes (both type 1 and type 2), epilepsy, hypothyroidism, obesity, sleep disorders, asthma, chronic liver disease, chronic kidney disease and chronic respiratory disease compared to people with DS without a COVID-19 diagnosis. For controls, those with a COVID-19 diagnosis had higher rates of congenital heart disease, anxiety disorders, other chronic inflammatory conditions/other autoimmune conditions, depression, diabetes (both type 1 and type 2), hypertension, hypothyroidism, obesity, other cardiovascular diseases, sleep disorders, smoking, asthma and chronic respiratory disease compared to those without COVID-19.
Unadjusted for comorbidities listed in Table 1, we found that DS cases had an increased likelihood of receiving a COVID-19 diagnosis compared to controls (Table 2). In a model adjusted for comorbidities, COVID-19 diagnosis was most strongly associated with dementia (OR = 2.75, 95% CI 2.03–3.72), chronic respiratory disease excluding asthma, epilepsy, hypertension, asthma, depression, anxiety disorders and other chronic inflammatory conditions/other autoimmune conditions explaining increased susceptibility of COVID-19 diagnosis. DS was not independently associated with COVID-19 after adjusting for comorbidities.
Interactions Between Comorbidities and Susceptibility to COVID-19 Diagnosis
Comorbidities from our previous models were chosen based on their clinical relevance; these included chronic respiratory disease, asthma and dementia. We found evidence that the association of DS with COVID-19 varied by chronic respiratory disease status. People with DS who had a chronic respiratory disease were more susceptible to being diagnosed with COVID-19, OR = 1.71 (95% CI 1.20–2.43), p = 0.003. Interactions with asthma (p = 0.28) and dementia (p = 0.36) diagnosis did not improve goodness of fit.
Risk Associated with Multimorbidity
As Table 3 shows, multimorbidity was associated with increased susceptibility to a COVID-19 diagnosis compared to having no comorbidities. Adjusting for multimorbidity, people with DS were still more likely to receive a COVID-19 diagnosis compared to controls.
Impact of Living Situation on Susceptibility to COVID-19
To examine the effect of living situation on the DS and chronic respiratory disease diagnosis interaction, we fitted a standard logistic regression on a sub-sample of 4528 patients (10.4% of total sample) who had data on their living situation. Living situation data was coded as per the OpenSAFELY study20 comparing those living in residential or care settings with those in other living situations (living with relatives etc.).
When adjusting for the impact of living in residential or care settings, the DS and chronic respiratory disease diagnosis interaction was not significant, OR = 1.83 (95% CI 0.86–4.28), p = 0.14. In this model, age groups 50–59 (OR = 4.32; 95% CI 1.30–26.80; p = 0.04); 60–59 (OR = 4.70; 95% CI 1.38–29.49; p = 0.04) and 70–79 (OR = 5.02; 95% CI 1.29–33.37; p = 0.04), epilepsy (OR = 1.46; 95% CI 1.14–1.84; p = 0.002) and living in residential or care settings (OR = 1.60; 95% CI 1.27–2.01; p < 0.0001) were associated with increased likelihood of a COVID-19 diagnosis.