New-onset neurodegenerative diseases as long-term sequelae of SARS-CoV-2 infection: A systematic review and meta-analysis

The association between SARS-CoV-2 infection with increased risk for new-onset neurodegenerative diseases remains unclear. Therefore, this meta-analysis aims to elucidate whether new-onset neurodegenerative diseases are long-term sequelae of SARS-CoV-2 infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched for articles published up to January 10, 2023. A systematic review and meta-analysis were performed to calculate the pooled effect size, expressed as hazard ratios (HR) with corresponding 95% confidence interval (CI) of each outcome. Twelve studies involving 33 146 809 individuals (2 688 417 post-COVID-19 cases and 30 458 392 controls) were included in the present meta-analysis. The pooled analyses compared with control groups showed a significant association between SARS-CoV-2 infection and increased risk for new-onset Alzheimer's disease (HR = 1.50, 95% CI 1.22–1.85, I² = 97%), dementia (HR = 1.66, 95% CI 1.42–1.94, I² = 91%), and Parkinson's disease (HR = 1.44, 95% CI 1.06–1.95, I² = 86%) among COVID-19 survivors. SARS-CoV-2 infection may be associated with a higher risk for new-onset neurodegenerative diseases in recovered COVID-19 patients. Future studies are warranted to determine the biological mechanisms underlying the neurodegenerative consequences of COVID-19 as long-term sequelae of SARS-CoV-2 infection.