Journal Article

Risk of neuropsychiatric and related conditions associated with SARS-CoV-2 infection: a difference-in-differences analysis

Lei, Yuqing, Utidjian, Levon H., Jones, W. Schuyler, Hornig, Mady, Keebler, Amber Brown, Lu, Yiwen, Zhou, Ting, Becich, Michael J., Kelleher, Kelly, Elia, Josephine, Blecker, Saul, Christakis, Dimitri A., Mosa, Abu Saleh Mohammad, Taylor, Bradley W., Chen, Yong, Williams, David A., Zhang, Dazheng, Jhaveri, Ravi, Schwenk, Hayden T., Hornig-Rohan, Maxwell M., Pajer, Kathleen, Kim, Susan, Aragon, Leyna V., Platt, Jonathan, Li, Lu, Prasad, Raghuram, Chen, Jiajie, Forrest, Christopher B., Tong, Jiayi, Blum, Nathan J.

2025

Overview

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. The COVID-19 pandemic has raised concerns about increased neuropsychiatric conditions in children and youths, with potential links to SARS-CoV-2 infection. Here, the authors analyze EHR data from 25 institutions, showing that COVID-19 positive children and youths have a modestly increased risk of developing neuropsychiatric conditions, such as anxiety, depression, and ADHD, compared to those who tested negative.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/326/596/4130 / 692/308/174 / 692/617 / 692/699/476 / Adolescent / Age / Anxiety / Anxiety - epidemiology / Attention Deficit Disorder with Hyperactivity - epidemiology / Attention deficit hyperactivity disorder / Autism / Autistic Disorder - epidemiology / Body mass index / Child / Child, Preschool / Children / COVID-19 / COVID-19 - complications / COVID-19 - epidemiology / COVID-19 - psychology / Depression - epidemiology / Electronic health records / Female / Gender dysphoria / Health risks / Humanities and Social Sciences / Humans / Infections / Male / Mental depression / Mental Disorders - epidemiology / multidisciplinary / Obsessive-Compulsive Disorder - epidemiology / Pandemics / Pediatrics / Psychosis / Retrospective Studies / Risk Factors / SARS-CoV-2 - isolation & purification / Science / Science (multidisciplinary) / Serology / Severe acute respiratory syndrome coronavirus 2 / Sexual disorders / Suicidal ideation / Viral diseases / Young Adult