SARS-CoV-2 susceptibility and COVID-19 illness course and outcome in people with pre-existing neurodegenerative disorders: Systematic review with frequentist and Bayesian meta-analyses

Background People with neurodegenerative disease and mild cognitive impairment (MCI) may have an elevated risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may be disproportionally affected by coronavirus disease 2019 (COVID-19) once infected. Aims To review all eligible studies and quantify the strength of associations between various pre-existing neurodegenerative disorders and both SARS-CoV-2 susceptibility and COVID-19 illness course and outcome. Method Pre-registered systematic review with frequentist and Bayesian meta-analyses. Systematic searches were executed in PubMed, Web of Science and preprint servers. The final search date was 9 January 2023. Odds ratios (ORs) were used as measures of effect. Results In total, 136 primary studies (total sample size n = 97 643 494), reporting on 268 effect-size estimates, met the inclusion criteria. The odds for a positive SARS-CoV-2 test result were increased for people with pre-existing dementia (OR = 1.83, 95% CI 1.16-2.87), Alzheimer's disease (OR = 2.86, 95% CI 1.44-5.66) and Parkinson's disease (OR = 1.65, 95% CI 1.34-2.04). People with pre-existing dementia were more likely to experience a relatively severe COVID-19 course, once infected (OR = 1.43, 95% CI 1.00-2.03). People with pre-existing dementia or Alzheimer's disease were at increased risk for COVID-19-related hospital admission (pooled OR range: 1.60-3.72). Intensive care unit admission rates were relatively low for people with dementia (OR = 0.54, 95% CI 0.40-0.74). All neurodegenerative disorders, including MCI, were at higher risk for COVID-19-related mortality (pooled OR range: 1.56-2.27). Conclusions Our findings confirm that, in general, people with neurodegenerative disease and MCI are at a disproportionally high risk of contracting COVID-19 and have a poor outcome once infected.