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Cognitive Disorders are a Risk Factor for Severe COVID-19

Alzheimer’s disease, dementia, and genetic variations in areas key to viral infection are risk factors for severe COVID-19 a new study suggests.

Cognitive disorders, such as Alzheimer’s disease and dementia, are associated with a greater risk of severe coronavirus disease 2019 (COVID-19), an analysis by investigators at the University of Georgia found.

“Special care is needed to protect these individuals from contracting the virus,” the study’s senior author Kaixiong (Calvin) Ye, PhD, assistant professor in the Institute of Bioinformatics and Department of Genetics at the University of Georgia, told Contagion®.

The observational cohort study, published in Brain Behavior and Immunity, used data from the UK Biobank, which was established in 2006 to study genetic and nongenetic determinants of diseases and includes data on about 1,000 diseases. Investigators analyzed data on 389,620 hospitalized patients in England, including 1,091 who tested positive for COVID-19.

“I would say there were two major surprises in our study,” Ye said. “1) We expect individuals with pre-existing conditions, such as obesity and type 2 diabetes, are at a higher risk of severe COVID-19. We did observe these two conditions in our sample of hospitalized COVID-19 patients. However, cognitive disorders turn out to be an even stronger risk factor. For comparison, in our data, having type 2 diabetes increases the odds of hospitalized COVID-19 by 25%, while having Alzheimer’s disease increases the odds by 130%.

“2) We also found other less well-known pre-existing conditions that increase the risk of severe COVID-19, such as varicose veins and bone fracture. These risk factors are identified for the first time in our study. Together with cognitive disorders, they suggest that individuals who have impaired self-care ability are at an increased risk. This is likely because they have more interactions with care providers and more likely to contract the virus.”

Results of the study concluded Alzheimer’s disease was the most significant risk factor (odds ratio = 2.29, 95% confidence interval: 1.25–4.16), followed by dementia (OR = 2.16, 95% CI: 1.36–3.42) and the overall category of delirium, dementia, amnestic and other cognitive disorders (OR = 1.90, 95% CI:1.24–2.90).

Investigators also focused on two genes — angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 — which play a role in the entry of SAR-CoV-2 into human cells and found that genetic variations were associated with severe COVID-19. Previously, genetic variants around TMPRSS2 were found to be associated with conditions including prostate cancer and heart failure.

“We still don't know the exact mechanism that makes patients with cognitive disorders more likely to have severe COVID-19,” Ye said. “It could be because of their increased chance of exposure to the virus. But it is also possible that cognitive disorders exacerbate the progress of COVID-19 after virus infection. Additional comparisons among severe COVID-19 patient, mild/asymptomatic COVID-19 patients, and non-COVID-19 patients will provide us more insights.”

Understanding genetic and nongenetic risk factors for COVID-19 can help target responses to the pandemic and prevention efforts. A recent study looked at developing a risk score model to predict mortality in COVID-19 patients, using demographic, clinical and outcome data and factoring in comorbidities including dementia and chronic neurological conditions.

While Ye’s study looked at cognitive disorders as a risk factor for COVID-19, other research has examined psychiatric manifestations of the disease, including deterioration of dementia.