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

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.

Fig. 1

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

Fig. 2. Risk difference of post-acute COVID-19 neuropsychiatric and related conditions in children aged 5–11, compared to the COVID-19-negative cohort.

Outcomes include cluster-level conditions across 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 refers to the occurrence of any listed neuropsychiatric or related condition. The sample size was 141,349 for the COVID-19 positive group and 441,790 for the COVID-19 negative group. Risk differences and 95% confidence intervals are shown. Red lines indicate statistically significant differences (p < 0.05), while gray lines indicate non-significant findings. P-values were calculated using two-sided t-tests; no adjustments were made for multiple comparisons.

Fig. 3. Risk difference of post-acute COVID-19 neuropsychiatric and related conditions in youths aged 12 to 20, compared to the COVID-19-negative cohort.

Outcomes include cluster-level conditions across 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 refers to the occurrence of any listed neuropsychiatric or related condition. The sample size was 184,725 for the COVID-19 positive group and 445,524 for the COVID-19 negative group. Risk differences and 95% confidence intervals are shown. Red lines indicate statistically significant differences (p < 0.05), while gray lines indicate non-significant findings. P values were calculated using two-sided t tests; no adjustments were made for multiple comparisons.