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

Author

Listed:
  • Yiwen Lu

    (University of Pennsylvania
    University of Pennsylvania)

  • Jiayi Tong

    (University of Pennsylvania
    University of Pennsylvania
    Johns Hopkins Bloomberg School of Public Health)

  • Dazheng Zhang

    (University of Pennsylvania
    University of Pennsylvania)

  • Jiajie Chen

    (University of Pennsylvania
    University of Pennsylvania)

  • Lu Li

    (University of Pennsylvania
    University of Pennsylvania)

  • Yuqing Lei

    (University of Pennsylvania
    University of Pennsylvania)

  • Ting Zhou

    (University of Pennsylvania
    University of Pennsylvania)

  • Leyna V. Aragon

    (or Community Advocate Representative
    Health Sciences Center)

  • 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
    Northwell Health)

  • 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
    University of Alabama at Birmingham)

  • 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
    University of Pennsylvania
    University of Pennsylvania
    Leonard Davis Institute of Health Economics)

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.

Suggested Citation

  • 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 & Maxwe, 2025. "Risk of neuropsychiatric and related conditions associated with SARS-CoV-2 infection: a difference-in-differences analysis," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61961-1
    DOI: 10.1038/s41467-025-61961-1
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    References listed on IDEAS

    as
    1. Bingyu Zhang & Deepika Thacker & Ting Zhou & Dazheng Zhang & Yuqing Lei & Jiajie Chen & Elizabeth A. Chrischilles & Dimitri A. Christakis & Soledad Fernandez & Vidu Garg & Susan Kim & Abu S. M. Mosa &, 2025. "Cardiovascular post-acute sequelae of SARS-CoV-2 in children and adolescents: cohort study using electronic health records," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    2. Martin Roessler & Falko Tesch & Manuel Batram & Josephine Jacob & Friedrich Loser & Oliver Weidinger & Danny Wende & Annika Vivirito & Nicole Toepfner & Franz Ehm & Martin Seifert & Oliver Nagel & Chr, 2022. "Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany," PLOS Medicine, Public Library of Science, vol. 19(11), pages 1-22, November.
    3. Dazheng Zhang & Bingyu Zhang & Qiong Wu & Ting Zhou & Jiayi Tong & Yiwen Lu & Jiajie Chen & Huiyuan Wang & Deena J. Chisolm & Ravi Jhaveri & Rachel C. Kenney & Russell L. Rothman & Suchitra Rao & Davi, 2025. "Racial/ethnic differences in post-acute sequelae of SARS-CoV-2 in children and adolescents in the United States," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    4. Salima Meherali & Neelam Punjani & Samantha Louie-Poon & Komal Abdul Rahim & Jai K. Das & Rehana A. Salam & Zohra S. Lassi, 2021. "Mental Health of Children and Adolescents Amidst COVID-19 and Past Pandemics: A Rapid Systematic Review," IJERPH, MDPI, vol. 18(7), pages 1-16, March.
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