Does SARS-CoV-2 Infection Increase Risk of Neuropsychiatric and Related Conditions? Findings from Difference-in-Differences Analyses

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 aimed 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 conducted a retrospective analysis of 326,074 COVID-19 positive and 887,314 negative participants matched for risk factors and stratified by age. Neuropsychiatric outcomes were examined 28 to 179 days post-infection or negative test between March 2020 and December 2022. SARS-CoV-2 positivity was confirmed via PCR, serology, or antigen tests, while negativity required negative test results and no related diagnoses. Risk differences revealed higher frequencies of neuropsychiatric conditions in the COVID-19 positive cohort. Children faced increased risks for anxiety, OCD, ADHD, autism, and other conditions, while youths exhibited 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.

Figure 1

Selection of participants for both COVID-19-positive and COVID-19-negative patients, stratified by age (children and youths).

Figure 2

Risk Difference of post-acute COVID-19 neuropsychiatric and related conditions compared with the COVID-19-negative cohort in children (age 5~11). Outcomes consisted of multiple cluster level conditions in adverse childhood experiences, anxiety disorders, disruptive behavior disorders, eating and feeding disorders, elimination disorders, gender dysphoria/sexual dysfunction, intentional self-harm/suicidality, mood disorders, neurocognitive disorders, neurodevelopmental disorders, personality disorders, psychotic disorders, sleep-wake disorders, standalone symptoms, substance use and dependence, and tic disorders. The composite outcome (any neuropsychiatric and related conditions) refers to occurrence of any neuropsychiatric and related outcome listed.

Figure 3

Risk Difference of post-acute COVID-19 neuropsychiatric and related conditions compared with the COVID-19-negative cohort in youths (age 12~20). Outcomes consisted of multiple cluster level conditions in adverse childhood experiences, anxiety disorders, disruptive behavior disorders, eating and feeding disorders, elimination disorders, gender dysphoria/sexual dysfunction, intentional self-harm/suicidality, mood disorders, neurocognitive disorders, neurodevelopmental disorders, personality disorders, psychotic disorders, sleep-wake disorders, standalone symptoms, substance use and dependence, and tic disorders. The composite outcome (any neuropsychiatric and related conditions) refers to occurrence of any neuropsychiatric and related outcome listed.