Does COVID-19 increase the risk of neuropsychiatric sequelae? Evidence from a mendelian randomization approach

Abstract

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.