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

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 and Yong Chen ()
Additional contact information
Yiwen Lu: University of Pennsylvania
Jiayi Tong: University of Pennsylvania
Dazheng Zhang: University of Pennsylvania
Jiajie Chen: University of Pennsylvania
Lu Li: University of Pennsylvania
Yuqing Lei: University of Pennsylvania
Ting Zhou: University of Pennsylvania
Leyna V. Aragon: or Community Advocate Representative
Michael J. Becich: University of Pittsburgh School of Medicine
Saul Blecker: NYU Grossman School of Medicine
Nathan J. Blum: Children’s Hospital of Philadelphia
Dimitri A. Christakis: Seattle Children’s Research Institute
Mady Hornig: or Community Advocate Representative
Maxwell M. Hornig-Rohan: or Community Advocate Representative
Ravi Jhaveri: Ann & Robert H. Lurie Children’s Hospital of Chicago
W. Schuyler Jones: Duke University Health System
Amber Brown Keebler: University of Nebraska Medical Center
Kelly Kelleher: The Ohio State University College of Medicine
Susan Kim: Benioff Children’s Hospital
Abu Saleh Mohammad Mosa: University of Missouri School of Medicine
Kathleen Pajer: Ottawa
Jonathan Platt: The University of Iowa College of Public Health
Hayden T. Schwenk: Division of Pediatric Infectious Diseases
Bradley W. Taylor: The Medical College of Wisconsin
Levon H. Utidjian: Children’s Hospital of Philadelphia
David A. Williams: University of Michigan
Raghuram Prasad: the University of Pennsylvania
Josephine Elia: Sydney Kimmel School of Medicine
Christopher B. Forrest: Children’s Hospital of Philadelphia
Yong Chen: University of Pennsylvania

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-61961-1

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