Approved Research

Is there an association between genetic risk factors for neurodegenerative disorders and COVID-19 susceptibility?

Lay summary

Understanding the biological mechanisms of COVID-19 is an urgent goal due to its severe consequences for society, leading to thousands of deaths worldwide (> 400K registered deaths) and to severe health system and economic problems. Thus, it is crucial to  disentangle molecular mechanisms, risk factors, transmission rates and every other aspect related to this disease, to avoid or mitigate the devastating effects of this pandemic. Our proposal aims to investigate the genetic variants in the population that are associated with the severity of COVID-19 manifestation. Once such associations are found, they could point to risk factors or genotypes more likely to be involved with the vulnerability of individuals to COVID-19 infection.

COVID-19 has emerged in the worldwide population with a wide spectrum of symptoms, ranging from asymptomatic individuals, to mildly affected patients, to patients exhibiting severe conditions requiring intensive care. Several studies have shown preexistent comorbidities as risk factors for COVID-19, such as hypertension, type II diabetes, cardiovascular and respiratory diseases, among others. Recently, studies have reported that COVID-19-positive patients were more likely to have dementia compared to patients from other disease groups. Likewise, genetic association of an APOE variant to severity of COVID-19 phenotype was observed. APOE gene is well known to be involved with Alzheimer's disease, suggesting that neurological impairments could be correlated to COVID-19 phenotype and a risk factor for virus infection. Moreover, poor neurological conditions have been observed in about 20-30% COVID-19 infected patients. Despite the small sample sizes of those studies, the literature shows that other viral infections can cause a neuroinflammatory process that lead to blood-brain barrier breakdown and triggers early manifestations of neurodegeneration processes. Unraveling the genetic factors that are associated with COVID-19 susceptibility could thus help in the identification of additional risk factors and prevent or limit the pathological neurodegeneration.

Our proposal is to study the possible association of known SNP variants related to neurodegeneration risk factors with COVID-19 phenotype in the UK Biobank. Quality control of genotypes will be evaluated. A logistic regression model comparing the genotype to COVID-19 phenotype will be performed with appropriate adjusted variables. These results can increase our understanding of the molecular bases of COVID-19 infection vulnerability and risk factors, which may help in the management of the current and future outbreaks. Moreover, results may support the proposal of early interventions to limit  brain pathology in surviving patients.