ABSTRACT
Introduction During the COVID-19 pandemic, pre-existing dementia was associated with a 3x increase in risk of hospitalisation and (25.6%) of COVID-19 related deaths had dementia. However, it is unclear whether people living with dementia are at higher risk of COVID-19 due to dementia or whether there may be a biologically plausible link between dementia and COVID-19. The ApoE e4 allele is highly associated with dementia. We aimed to test the COVID-19 risk associated with dementia and the association between ApoE e4e4 allele and COVID-19 with the aim of clarifying biological vulnerability. Methods UK Biobank (England) participants baseline (2006 to 2010), plus secondary care data to 2017. Separate analysis tested dementia and ApoE genotype association with COVID-19 status (16th March-31st May 2020) or mortality (to March 31, 2020, plus incomplete deaths from April, 2020) in logistic models, adjusted for demographics and technical covariates. Results In 269,070 participants aged 65+, including 507(0.2%) hospitalized COVID-19 patients, those with pre-existing dementia were at increased risk of being hospitalized for COVID-19 (OR = 3.50 95% CI 1.93 to 6.34) and also for COVID-19 and death (OR = 7.30 95% CI 3.28–16.21). In 375,689 European-ancestry UKB participants, ApoE e4e4 homozygotes were more likely to be COVID-19 test positives (reaching genome-wide significance: OR = 2.24, 95% CI:1.72–2.93, p = 3.24 × 10–9) and of mortality with test-confirmed COVID-19 (OR = 4.29, 95% CI: 2.38–7.72, p = 1.22 × 10–6), compared to e3e3s homozygotes. The associations were little changed in subsets of participants who were free of diseases associated with ApoE e4 and COVID-19 severity. Conclusion Dementia was found to be disproportionally common in older adults who develop severe COVID-19. We have shown a plausible genetic pathway of increased COVID-19 risk with dementia, therefore suggesting that the positive association between dementia and COVID-19 is not just the result of high cases of COVID-19 in care homes.
ABSTRACT
Background Older adults are at increased risk of COVID-19, resulting in public health shielding measures for all adults over 70 in the UK. Frailty has been proposed for risk stratification in COVID-19 with limited evidence. Cardiovascular risk factors hypertension, diabetes and raised BMI have been associated with increased COVID-19 risk. We sought to test if non-frail older adults with low cardiovascular risk had reduced COVID-19, to inform targeted shielding policies. Methods Fried and Rockwood frailty were ascertained at UK Biobank baseline (2006-2010) and electronic frailty index(eFI) in primary care data to 2017*. A cardiovascular disease risk score(CRS) consisting of smoking status, LDL-cholesterol, blood pressure, BMI, fasting glucose and physical activity was estimated at baseline. Frailty (baseline and eFI;eFI alone) and CRS were tested in logistic models against COVID-19 status and COVID-19 mortality to 14th June 2020 adjusted for demographics and technical covariates. Results N=269,164 UKB participants aged ≥65 at baseline (≥75years in 2020). 13.9% of COVID-19 positive were non-frail with low baseline CRS versus 41.8% frail with moderate/high CRS. Being non-frail and having low CRS were independently associated with reduced COVID-19. The composite of non-frail with low CRS compared to frail with moderate/high CRS had significantly reduced COVID-19 risk (composite non-frail with low CRS HR 0.61;95% CI 0.45-0.84;p=0.0023;eFI non-frail with low CRS HR 0.16;95%CI 0.07-0.36;p value=9.9x10-6) and COVID-19 mortality (composite non-frail HR 0.28;95% CI 0.10-0.82;pvalue=0.02;eFI non-frail 0.07;95% CI 0.02-0.28;pvalue=0.00014). Conclusion These results show that the COVID-19 risk in non-frail older adults with low cardiovascular risk was up to 84% lower than in those who were frail with cardiovascular risk factors. This could contribute to future work on stratification of shielding risk in older adults in future COVID-19 surges. *Planned data updates prior to the conference should enable updates to 2020.
ABSTRACT
Introduction: During the COVID-19 pandemic, pre-existing dementia was associated with a 3x increase in risk of hospitalisation and (25.6%) of COVID-19 related deaths had dementia. However, it is unclear whether people living with dementia are at higher risk of COVID-19 due to dementia or whether there may be a biologically plausible link between dementia and COVID-19. The ApoE e4 allele is highly associated with dementia. We aimed to test the COVID-19 risk associated with dementia and the association between ApoE e4e4 allele and COVID-19 with the aim of clarifying biological vulnerability. Methods: UK Biobank (England) participants baseline (2006 to 2010), plus secondary care data to 2017. Separate analysis tested dementia and ApoE genotype association with COVID-19 status (16th March-31st May 2020) or mortality (to March 31, 2020, plus incomplete deaths from April, 2020) in logistic models, adjusted for demographics and technical covariates. Results: In 269,070 participants aged 65+, including 507(0.2%) hospitalized COVID- 19 patients, those with pre-existing dementia were at increased risk of being hospitalized for COVID-19 (OR=3.50 95% CI 1.93 to 6.34) and also for COVID-19 and death (OR=7.30 95% CI 3.28–16.21). In 375,689 European-ancestry UKB participants, ApoE e4e4 homozygotes were more likely to be COVID-19 test positives (reaching genome-wide significance: OR=2.24, 95% CI:1.72–2.93, p=3.24×10–9) and of mortality with testconfirmed COVID-19 (OR=4.29, 95% CI: 2.38–7.72, p=1.22×10–6), compared to e3e3s homozygotes.The associations were little changed in subsets of participants who were free of diseases associated with ApoE e4 and COVID-19 severity. Conclusion: Dementia was found to be disproportionally common in older adults who develop severe COVID-19. We have shown a plausible genetic pathway of increased COVID-19 risk with dementia, therefore suggesting that the positive association between dementia and COVID-19 is not just the result of high cases of COVID-19 in care homes.