Risk of neuropsychiatric and related conditions associated with SARS-CoV-2 infection: a difference-in-differences analysis
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
- Dimitri Christakis (ORCID: https://orcid.org/0000-0003-0726-7253)
- Christopher B. Forrest (ORCID: https://orcid.org/0000-0003-1252-068X)
- W. Schuyler Jones (ORCID: https://orcid.org/0000-0002-7288-9596)
- Jiayi Tong (ORCID: https://orcid.org/0000-0002-1213-6699)
- Dazheng Zhang (ORCID: https://orcid.org/0000-0002-1431-0785)
- Jonathan Platt (ORCID: https://orcid.org/0000-0002-5475-0494)
- Hayden T. Schwenk (ORCID: https://orcid.org/0000-0002-8164-8655)
- Ravi R. Jhaveri (ORCID: https://orcid.org/0000-0001-9921-0419)
- David A. Williams (ORCID: https://orcid.org/0000-0002-5052-4895)
- Abu Saleh Mohammad Mosa (ORCID: https://orcid.org/0000-0002-8956-1466)
- Lu Li (ORCID: https://orcid.org/0000-0002-2891-6067)
- Nathan J. Blum (ORCID: https://orcid.org/0000-0002-1259-4331)
- Mady Hornig (ORCID: https://orcid.org/0000-0001-7572-3092)
- Bradley Taylor (ORCID: https://orcid.org/0000-0002-6414-4172)
- Kathleen Pajer (ORCID: https://orcid.org/0000-0002-3699-9966)
- Josephine Elia (ORCID: https://orcid.org/0000-0002-5037-1622)
- Levon Utidjian
- Kelly J. Kelleher (ORCID: https://orcid.org/0000-0002-4420-8044)
- Michael J. Becich (ORCID: https://orcid.org/0000-0001-5998-8074)
- Saul Blecker (ORCID: https://orcid.org/0000-0003-4460-1046)
- Leyna Aragon (ORCID: https://orcid.org/0009-0001-9429-0218)
- Yong Chen (ORCID: https://orcid.org/0000-0003-0835-0788)
- Susan Kim (ORCID: https://orcid.org/0000-0003-2159-8059)
- Yuqing Lei (ORCID: https://orcid.org/0009-0003-8867-202X)
- Ting Zhou (ORCID: https://orcid.org/0000-0003-3199-4354)
- Jiajie Chen (ORCID: https://orcid.org/0009-0008-7402-6883)
- Amber Brown Keebler (ORCID: https://orcid.org/0000-0002-7246-2859)
- Yiwen Lu
- Raghuram Prasad
- Maxwell M. Hornig-Rohan (ORCID: https://orcid.org/0009-0005-0985-0225)
Institutions
- University of Iowa (US)
- Lurie Children's Hospital (US)
- Seattle Children's Hospital (US)
- Northwell Health (US)
- Nationwide Children's Hospital (US)
- Feinstein Institute for Medical Research (US)
- Children's Hospital of Philadelphia (US)
- Johns Hopkins University (US)
- University of New Mexico (US)
- University of Pittsburgh (US)
- Medical College of Wisconsin (US)
- University of the Philippines Mindanao (PH)
- University of Michigan (US)
- Children's Hospital of Eastern Ontario (CA)
- University of the Arts (US)
- University of Alabama at Birmingham (US)
- Clinical Research Institute (US)
- Nemours Children's Health System (US)
- Penn Center for AIDS Research (US)
- Applied Mathematics (United States) (US)
- UCSF Benioff Children's Hospital (US)
- Stanford Medicine (US)
- Duke University Health System (US)
- Patient Advocate Foundation (US)
- New York University (US)
- University of Nebraska Medical Center (US)
- University of Missouri (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-07-24
- DOI
- https://doi.org/10.1038/s41467-025-61961-1
- Citations
- 4
- Primary Topic
- Long-Term Effects of COVID-19
- Type
- article
- Field-Weighted Citation Impact
- 5.56
Funders
- National Institutes of Health