Corona virus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared to be a pandemic on 11th of March, 2020 by the World Health Organization. Many countries affected by COVID-19 epidemic have found their health care services overwhelmed in the past few months due to need for hospitalization in people with severe disease. The last few months of the COVID-19 epidemic have led to a large number of publications. We identify three broad areas that remain unexplored and are the focus of the current project. 1) Research on identification of risk factors for severe COVID-19 (hospitalization or death) being based on a limited set of risk factor assessed at hospitalization, primarily in univariate analyses. 2) COVID-19 is primarily a respiratory disease; it can wreak havoc on the kidneys, liver, heart, brain, and perhaps other organ systems in the body. Much of this impact is difficult to ascertain for the lack of previous functional status of persons. 3) Although ADRD is the most common comorbidity in COVID-19 deaths the intersection between these two diseases is unclear.
We aim to add to current knowledge by adding a longitudinal component to study risk factors for COVID-19 and its consequences on ageing. The three aims of this project address crucial gaps in the literature.
Aim 1 will construct a risk score for adverse COVID-19 (hospitalization or mortality) using a wide array of risk factors. Further analyses will examine whether these are different in those with ADRD/cognitive impairment.
Aim 2 will quantify the impact of COVID-19 and its severity on lung, cardiovascular, kidney, physical and cognitive function in the proposed Whitehall COVID-19 sub-study on 2000 participants, and assess whether these changes are magnified in persons with ADRD/cognitive impairment.
Aim 3 will compare severe COVID-19 (hospitalization and mortality) in those with and without ADRD/cognitive impairment. The role of APOE genotype and risk factors (social behavioral, biologic) to explain these differences will be examined. A further component of this aim is to examine the role of COVID-19 (hospitalization and mortality) in transitions to ADRD in those with cognitive impairment and those free of cognitive impairment before the epidemic

Public Health Relevance

Age is the primary risk factor for severe COVID-19 and Alzheimer?s disease and related dementias (ADRD) the most common comorbidity in COVID-19 deaths in older deaths. Our urgent competitive revision aims to examine the intersection of ADRD and COVID-19 using the Whitehall study where risk factors (social, behavioral, biologic, and health-related), functioning (cardiovascular, cognitive, motor), and cognitive status (cognitive impairment and ADRD) have been perfectly characterized since 1985 using repeat clinical assessments. We aim to construct a multifactorial risk algorithm for severe COVID-19, and assess its performance in those with ADRD/cognitive impairment; examine change in functioning due to COVID-19 (in survivors post-hospitalization), and examine whether COVID-19 accelerates progression to clinical ADRD. This project is a good fit with the parent grants on ADRD and functioning.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Karraker, Amelia Wilkes
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University College London
United Kingdom
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