Cognitive disorders associated with hospitalization of COVID-19: Results from an observational cohort study

Highlights • An unbiased analysis of 974 diseases revealed new risk factors of severe COVID-19. • Delirium, dementia, amnestic, and other cognitive disorders increase its risk. • Genetic variants in SARS‑CoV‑2 infection genes are associated with severe COVID-19. • There is an urgent need for special dementia care during the pandemic.
Introduction Our understanding of risk factors for COVID‑19, including pre-existing medical conditions and genetic variations, is limited. To what extent the pre-existing clinical condition and genetic background have implications for COVID-19 still needs to be explored. Methods Our study included 389,620 participants of European descent from the UK Biobank, of whom 3,884 received the COVID-19 test and 1,091 were tested positive for COVID-19. We examined the association of COVID-19 status with an extensive list of 974 medical conditions and 30 blood biomarkers. Additionally, we tested the association of genetic variants in two key genes related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), with COVID-19 or any other phenotypes. Results The most significant risk factors for COVID-19 include Alzheimer’s disease (OR = 2.29, 95% CI: 1.25–4.16), 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). Evidence suggesting associations of genetic variants in SARS-CoV-2 infection-related genes with COVID-19 (rs7282236, OR = 1.33, 95% CI: 1.14–1.54, p = 2.31 × 10−4) and other phenotypes, such as an immune deficiency (p = 5.65 × 10−5) and prostate cancer (p = 1.1 × 10−5), was obtained. Conclusions Our unbiased and extensive search identified pre-existing Alzheimer’s disease and dementia as top risk factors for hospital admission due to COVID-19, highlighting the importance of providing special protective care for patients with cognitive disorders during this pandemic. We also obtained evidence suggesting a direct association of genetic variants with COVID-19.