Risk of neuropsychiatric and related conditions associated with SARS-CoV-2 infection: A difference-in-differences analysis
Lu, Y; Tong, J; Zhang, D; et al., Nature Communications
Published
July 2025
Journal
Nature Communications
Abstract
The COVID-19 pandemic has been associated with increased neuropsychiatric conditions in children and youths, with evidence suggesting that SARS-CoV-2 infection may contribute additional risks beyond pandemic stressors. This study aims to assess the full spectrum of neuropsychiatric conditions in COVID-19 positive children (ages 5-12) and youths (ages 12-20) compared to a matched COVID-19 negative cohort, accounting for factors influencing infection risk. Using EHR data from 25 institutions in the RECOVER program, we conduct a retrospective analysis of 326,074 COVID-19 positive and 887,314 negative participants matched for risk factors and stratified by age. Neuropsychiatric outcomes are examined 28 to 179 days post-infection or negative test between March 2020 and December 2022. SARS-CoV-2 positivity is confirmed via PCR, serology, or antigen tests, while negativity requires negative test results and no related diagnoses. Risk differences reveal higher frequencies of neuropsychiatric conditions in the COVID-19 positive cohort. Children face increased risks for anxiety, OCD, ADHD, autism, and other conditions, while youths exhibit elevated risks for anxiety, suicidality, depression, and related symptoms. These findings highlight SARS-CoV-2 infection as a potential contributor to neuropsychiatric risks, emphasizing the importance of research into tailored treatments and preventive strategies for affected individuals.
Authors
Yiwen Lu, Jiayi Tong, Dazheng Zhang, Jiajie Chen, Lu Li, Yuqing Lei, Ting Zhou, Leyna V Aragon, Michael J Becich, Saul Blecker, Nathan J Blum, Dimitri A Christakis, Mady Hornig, Maxwell M Hornig-Rohan, Ravi Jhaveri, W Schuyler Jones, Amber Brown Keebler, Kelly Kelleher, Susan Kim, Abu Saleh Mohammad Mosa, Kathleen Pajer, Jonathan Platt, Hayden T Schwenk, Bradley W Taylor, Levon H Utidjian, David A Williams, Raghuram Prasad, Josephine Elia, Christopher B Forrest, Yong Chen
Keywords
Humans; COVID-19/psychology/epidemiology/complications; Child; Adolescent; Male; Female; SARS-CoV-2/isolation & purification; Child, Preschool; Retrospective Studies; Risk Factors; Young Adult; Anxiety/epidemiology; Mental Disorders/epidemiology; Depression/epidemiology; Autistic Disorder/epidemiology; Attention Deficit Disorder with Hyperactivity/epidemiology; Obsessive-Compulsive Disorder/epidemiology