The Silent Impact: COVID-19's Neurological Legacy in Adolescents

Long-term neurological impacts of COVID-19 on adolescents reveal enduring challenges that demand urgent understanding and response, particularly in the context of post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID.

These neurological disturbances aren't merely stress-related for some adolescents and can persist, though trajectories vary and many improve over time; ongoing monitoring and support remain important.

COVID-19 infections can be associated with persistent inflammation and immune dysregulation, which are foundational to understanding the pandemic's impact on adolescent brains. Recent observations suggest that some adolescents post-COVID-19 exhibit biological changes that in some measures resemble those seen after early-life stress, based on observational studies, including patterns in cortisol regulation and inflammatory markers. Consistent biological changes akin to early-life stress illustrate these profound effects.

This intersection of neuroimmune pathways and inflammation likely contributes to prolonged neurological disturbances, manifesting as fatigue, cognitive impairments, and mood disorders. For many adolescents, pandemic-related stress has been associated in some studies with elevated cortisol and related cognitive or autonomic effects, though findings vary. Researchers report that these elevated levels are associated with neurodevelopmental and mental health challenges in adolescents, though causality is not established.

These changes do not occur in isolation but rather impact systemic health, altering adolescents’ physical and mental capacities, academic achievements, and social engagements—for example, some report reduced participation in sports and difficulty concentrating in class, with periods of increased fatigue at school.

Systemic implications require interdisciplinary strategies to tackle multifaceted post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID, in adolescents. Not all adolescents experience these outcomes equally, highlighting a diverse array of responses that reveal gaps in therapeutic strategies and the need for individualized, symptom-directed care.

Clinicians increasingly describe a spectrum of presentations in adolescents with PASC, ranging from headaches, difficulty concentrating, sleep disturbance, and orthostatic intolerance to mood symptoms and exercise intolerance. Courses vary: some adolescents recover within weeks to months, while others experience waxing-and-waning symptoms that disrupt school and social life. Clear communication with families about expected variability and warning signs helps set realistic goals and supports shared decision-making.

From a mechanistic standpoint, neuroimmune signaling and hypothalamic–pituitary–adrenal (HPA) axis dynamics are central to several proposed pathways. Peripheral inflammation may alter autonomic balance and fatigue perception, while sleep disruption and reduced activity during illness can perpetuate a cycle of deconditioning and cognitive inefficiency. These interacting pathways reinforce the need for gradual, individualized return-to-activity plans.

Functional impacts are often most visible in the classroom and on the field. Students may need shortened school days, rest breaks, or modified PE expectations during recovery. Athletic participation can be paced to symptoms, emphasizing hydration, orthostatic strategies, and stepwise conditioning rather than rapid return to high-intensity play. Collaboration with school nurses, counselors, and coaches can reduce setbacks and stigma.

Disparities and access barriers shape who is recognized and supported. Adolescents from underserved communities may face delayed evaluation, limited specialty access, or challenges obtaining school accommodations. Attention to language access, transportation, and mental health resources is critical to equitable care. Peer support and family education can buffer isolation and improve adherence to recovery plans.

Evaluation typically focuses on careful history, basic examination, and targeted testing guided by red flags. Many adolescents benefit from symptom clusters being addressed in parallel: sleep hygiene and cognitive load management; hydration and salt intake for orthostatic symptoms; paced activity for fatigue; and timely referral for mood or anxiety concerns. When available, interdisciplinary clinics can coordinate rehabilitation, autonomic assessment, and school reintegration plans.

Ongoing studies are working to identify clinical phenotypes, biomarkers of risk and recovery, and to test rehabilitation and mental health interventions tailored to adolescents. Multisite collaborations aim to harmonize outcome measures and follow youth longitudinally to understand who improves spontaneously, who benefits most from specific supports, and which strategies are scalable in schools and primary care.

Key takeaways:

• Post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) in adolescents spans neurological, cognitive, and mood symptoms linked to neuroimmune and HPA-axis changes, with courses that often improve but can persist.
• Presentation and impact are heterogeneous; equitable, individualized, symptom-directed care and school accommodations are central while definitive treatments remain limited.
• Assessment should prioritize exclusion of alternative diagnoses, functional impact, and mental health needs, with interdisciplinary follow-up when available.
• Research is rapidly evolving to define phenotypes, biomarkers of risk and recovery, and to test targeted rehabilitation and mental health interventions.