Published online Mar 19, 2022. doi: 10.5498/wjp.v12.i3.536
Peer-review started: November 12, 2021
First decision: December 12, 2021
Revised: January 3, 2022
Accepted: February 23, 2022
Article in press: February 23, 2022
Published online: March 19, 2022
Processing time: 125 Days and 22.1 Hours
Observational studies based on electronic health records (EHR) report an increased risk of neurological/neuropsychiatric sequelae for patients who have had coronavirus disease 2019 (COVID-19). However, these studies may suffer from biases such as unmeasured confounding, residual reverse causality, or lack of precision in EHR-based diagnoses. To rule out these biases, we tested causal links between COVID-19 and different potential neurological/neuropsychiatric sequelae through a two-sample Mendelian randomization analysis of summary statistics from large Genome-Wide Association Scans of susceptibility to COVID-19 and different neurological and neuropsychiatric disorders, including major depression, anxiety, schizophrenia, stroke, Parkinson’s and Alzheimer’s diseases. We found robust evidence suggesting that COVID-19 – notably the hospitalized and most severe forms – carries an increased risk of neuropsychiatric sequelae, particularly Alzheimer’s disease, and to a lesser extent anxiety disorder. In line with a large longitudinal EHR-based study, this evidence was stronger for more severe COVID-19 forms. These results call for a targeted screening strategy to tackle the post-COVID neuropsychiatric pandemic.
Core Tip: Inspired by suggestive findings of an increased incident risk of neurological and neuropsychiatric sequelae in people who have had coronavirus disease 2019 (COVID-19), we carried out a two-sample Mendelian randomization analysis to further investigate causality links and build evidence free of biases such as unmeasured confounding, residual reverse causality or lack of precision in electronic health record-based diagnoses. This analysis – typically applied to genetic associations from large genomic studies on the diseases of interest – indicated that the most severe forms of COVID-19 increased the risk of Alzheimer’s disease and anxiety, further supporting the findings of large observational studies.