ApoE e4e4 Genotype and Mortality With COVID-19 in UK Biobank

Kuo, Chia‐Ling; Pilling, Luke C.; Atkins, Janice L.; Masoli, Jane; Delgado, João; Kuchel, George A.; Melzer, David

doi:10.1093/gerona/glaa169

Cited by 91 publications

(75 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…ApoE2 and ApoE4 alleles are known to increase lipid levels and ApoE4 is further recognized as the strongest known genetic risk factor for Alzheimer’s disease ( 31 , 32 ). Recent analyses have also shown that homozygosity for ApoE4 was associated with significantly higher risk of SARS-CoV-2 infection as well as mortality from COVID-19, even after exclusion of subjects with potential confounding comorbidities, such as dementia, hypertension, type 2 diabetes, or CAD ( 33 , 34 ). Based on these observations, we evaluated whether previously reported associations between E4/E4 genotype and SARS-CoV-2-related outcomes could be due to effects on HDL cholesterol levels.…”

Section: Resultsmentioning

confidence: 99%

Association of serum HDL-cholesterol and apolipoprotein A1 levels with risk of severe SARS-CoV-2 infection

Hilser

Han

Biswas

et al. 2021

Journal of Lipid Research

View full text Add to dashboard Cite

Individuals with features of metabolic syndrome are particularly susceptible to SARS-CoV-2, a novel coronavirus associated with the severe respiratory disease COVID-19. Despite considerable attention dedicated to COVID-19, the link between metabolic syndrome and SARS-CoV-2 infection remains unclear. Using data from the UK Biobank, we investigated the relationship between severity of COVID-19 and metabolic syndrome-related serum biomarkers measured prior to SARS-CoV-2 infection. Logistic regression analyses were used to test biomarker levels and biomarker-associated genetic variants with SARS-CoV-2-related outcomes. Among SARS-CoV-2-positive cases and negative controls, a 10mg/dL increase in serum high-density lipoprotein (HDL) cholesterol or apolipoprotein A1 (ApoA1) levels was associated with ∼10% reduced risk of SARS-CoV-2 infection, after adjustment for age, sex, obesity, hypertension, type 2 diabetes, and coronary artery disease. Evaluation of known genetic variants for HDL cholesterol revealed that individuals homozygous for ApoE4 alleles had ∼2-3-fold higher risk of SARS-CoV-2 infection or mortality from COVID-19 compared to ApoE3 homozygotes, even after adjustment for HDL cholesterol levels. However, cumulative effects of all evaluated HDL cholesterol-raising alleles and Mendelian randomization analyses did not reveal association of genetically higher HDL cholesterol levels with decreased risk of SARS-CoV-2 infection. These results implicate serum HDL cholesterol and ApoA1 levels measured prior to SAR-CoV-2 exposure as clinical risk factors for severe COVID-19 infection but do not provide evidence that genetically elevated HDL cholesterol levels are associated with SAR-CoV-2 infection.

show abstract

Section: Resultsmentioning

confidence: 99%

Association of serum HDL-cholesterol and apolipoprotein A1 levels with risk of severe SARS-CoV-2 infection

Hilser

Han

Biswas

et al. 2021

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…The APOE-ε4 gene allele, the strongest genetic risk factor for AD, has been found to be linked to increased risk of infection and mortality due to COVID-19, although the biological mechanisms involved in this association remain to be known (Kuo et al, 2020). However, ACE2 expression has been reported to be reduced in mid-frontal brain tissue in AD patients, particularly in those carrying an APOE ε4 allele, and this reduction was negatively correlated with Aβ and phosphorylated tau pathology (Kehoe et al, 2016).…”

Section: Mechanisms Involved In Cognitive and Neuropsychiatric Manifementioning

confidence: 99%

Cognitive and Neuropsychiatric Manifestations of COVID-19 and Effects on Elderly Individuals With Dementia

Alonso‐Lana

Marquié

Ruiz

et al. 2020

Front. Aging Neurosci.

147

View full text Add to dashboard Cite

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide and has had unprecedented effects in healthcare systems, economies and society. COVID-19 clinical presentation primarily affects the respiratory system causing bilateral pneumonia, but it is increasingly being recognized as a systemic disease, with neurologic manifestations reported in patients with mild symptoms but, most frequently, in those in a severe condition. Elderly individuals are at high risk of developing severe forms of COVID-19 due to factors associated with aging and a higher prevalence of medical comorbidities and, therefore, they are more vulnerable to possible lasting neuropsychiatric and cognitive impairments. Several reports have described insomnia, depressed mood, anxiety, post-traumatic stress disorder and cognitive impairment in a proportion of patients after discharge from the hospital. The potential mechanisms underlying these symptoms are not fully understood but are probably multifactorial, involving direct neurotrophic effect of SARS-CoV-2, consequences of long intensive care unit stays, the use of mechanical ventilation and sedative drugs, brain hypoxia, systemic inflammation, secondary effects of medications used to treat COVID-19 and dysfunction of peripheral organs. Chronic diseases such as dementia are a particular concern not only because they are associated with higher rates of hospitalization and mortality but also because COVID-19 further exacerbates the vulnerability of those with cognitive impairment. In patients with dementia, COVID-19 frequently has an atypical presentation with mental status changes complicating the early identification of cases. COVID-19 has had a dramatical impact in long-term care facilities, where rates of infection and mortality have been very high. Community measures implemented to slow the spread of the virus have forced to social distancing and cancelation of cognitive stimulation programs, which may have contributed to generate loneliness, behavioral symptoms and worsening of cognition in patients with dementia. COVID-19 has impacted the functioning of Memory Clinics, research programs and clinical trials in the Alzheimer's field, triggering the

show abstract

“…The authors found that individuals homozygous for APOE ε 4 were more likely to test positive for COVID-19, and thus severe disease, compared the group homozygous for APOE ε 3 ( 9 ). Given the urgency for genetic determinants associated with COVID-19 severity, Kuo et al continued their investigation with the addition of more test results and mortality data ( 10 ). The study confirmed their initial findings, additionally reaching genome-wide significance for the association of APOE ε 4 ε 4 genotype with COVID-19 test positivity.…”

mentioning

confidence: 99%

“…Importantly, however, the less restrictive temporal parameters established in the follow-up study significantly undermine this premise. Nevertheless, the mortality data presented (calculated by quantifying deaths after confirmed positive) suggests increased disease severity in these subjects ( 10 ). Moreover, they reported that APOE ε 4 ε 4 genotype was associated with a 4-fold increase in mortality after testing positive relative to APOE ε 3 ε 3 individuals.…”

mentioning

confidence: 99%

Commentary: APOE e4 Genotype Predicts Severe COVID-19 in the UK Biobank Community Cohort

2020

View full text Add to dashboard Cite

ApoE e4e4 Genotype and Mortality With COVID-19 in UK Biobank

Cited by 91 publications

References 6 publications

Association of serum HDL-cholesterol and apolipoprotein A1 levels with risk of severe SARS-CoV-2 infection

Association of serum HDL-cholesterol and apolipoprotein A1 levels with risk of severe SARS-CoV-2 infection

Cognitive and Neuropsychiatric Manifestations of COVID-19 and Effects on Elderly Individuals With Dementia

Commentary: APOE e4 Genotype Predicts Severe COVID-19 in the UK Biobank Community Cohort

Contact Info

Product

Resources

About