Frailty & the Incidence and Course of COVID-19 among 500,000 Older Adults in the UK BIOBANK

Principal Investigators: Fuller-Thomson Esme R; Davison, Karen M, University of Toronto

In the absence of any available vaccine or cure for COVID-19, it is of utmost importance to develop improved screening techniques to correctly identify those most likely to develop severe illness and die from the disease. Many determinants, including genetic predisposition, nutrition, social, economic, health behaviours, chronic comorbid health conditions, and environmental factors, contribute to communicable diseases1 such as COVID-19. However, there is limited understanding of the relative importance of the individual and synergistic contributions of these determinants in relation to COVID-19. The majority of these factors are also associated with frailty. Older adults, particularly those living with frailty, are at high risk of hospitalization and death due to COVID-19. In addition to older age, the Centers for Disease Control and Prevention (CDC) have identified several other factors associated with higher risk of severe illness from COVID-19 including disabilities, a medical history of Chronic Obstructive Pulmonary Disease (COPD), asthma, heart conditions, diabetes, chronic kidney disease, liver disease, HIV/AIDS, obesity, and prolonged use of medications such as corticosteroids. Other characteristics that have been proposed as potential, but not yet established, risk factors include type A blood, low vitamin D blood levels, Black race, and some genetic variants (e.g., genes coding for receptors of the cell surface protein angiotensin-converting enzyme 2 (ACE2) may increase access of the coronavirus to airway cells)  Very little research attention has been paid to the potential risks associated with socio-demographic characteristics such as poverty and lack of social support, nutrient intake and other health behaviours, as well as environmental risk factors such as air pollution, neighborhood deprivation, and lack of neighborhood green space. We hypothesize that there is a wide range of interacting factors associated with the incidence and progression of COVID-19 among older adults living with frailty and that these may differ from risk factors among those living without frailty. Studies to date have been limited by small samples and retrospective data collection as opposed to drawing upon methodologically stronger, large, prospective studies. Without robust data, health professionals are unable to quickly and accurately identify the most vulnerable individuals for screening and targeted intervention. Our proposed innovative analyses will also search for and identify novel protective factors that improve disease prognosis in mid-age and older adults who are frail.

We propose to use the UK Biobank (UKB), a prospective cohort study of unprecedented depth and quality that started in 2006 with 500,000 British middle-age and older adults (currently aged 50-83), to examine how frailty, genetic predisposition, socio-demographic characteristics, health-related determinants, and environmental factors contribute to the incidence and prognosis of COVID-19. The UK government has invested more than $370 million CAD in gathering extensive information on half a million participants’ health and life course trajectories over the past 14 years. The secondary analyses we are proposing will leverage that investment to provide a cost-effective, comprehensive, prospective analysis to identify causal, risk, and protective factors associated with the incidence and prognosis of COVID-19 among frail older adults and their non-frail peers.