Howe de la Torre, S., Parlatini, V., & Cortese, S. (2023). Long-term central nervous system (CNS) consequences of COVID-19 in children. Expert Review of Neurotherapeutics, 23(8), 703–720. https://doi.org/10.1080/14737175.2023.2239500
- Neurological and neuropsychiatric symptoms are commonly reported in children and adolescents with long COVID, including headache, fatigue, cognitive difficulties, mood changes, and sleep problems
- Reported prevalence varies widely due to study heterogeneity, small sample sizes, and limited long-term follow-up
- Beyond mood and sleep issues, many neuropsychiatric conditions remain underexamined in pediatric long COVID
- Persistent symptoms may significantly affect daily functioning and well-being
Pediatric Long COVID: Neurological and Neuropsychiatric Symptoms
Children and adolescents typically experience mild or asymptomatic acute COVID-19. However, a significant subset develop persistent symptoms, commonly termed long COVID or post-COVID condition. Definitions in pediatrics are inconsistent. Some frameworks differentiate ongoing symptoms lasting 4 to 12 weeks from post-COVID syndrome beyond 12 weeks, while others use long COVID as a general term. This variability matters because symptoms are diverse, may fluctuate, and are often misattributed to stress, disrupted schooling, or normal adolescent development. The research base is also highly heterogeneous in study design, follow-up duration, and case definitions.
Three consistent findings emerge from the literature. First, neurological and mental health symptoms are frequently reported after pediatric SARS-CoV-2 infection. Second, prevalence estimates vary widely due to non-comparable study designs. Third, underlying mechanisms likely differ by symptom type and timing, so no single explanation accounts for all cases. A central clinical challenge is distinguishing infection-related effects from pandemic-related psychosocial stressors, such as isolation, disrupted routines, and anxiety, which can result in overlapping symptom profiles.
Key takeaways at a glance
- Pediatric long COVID may involve neurological symptoms such as headache, cognitive difficulties or brain fog, fatigue, changes in smell or taste, and dizziness.
- Neuropsychiatric symptoms, including sleep disturbances and mood or anxiety symptoms, are also reported.
- Less common presentations include obsessive-compulsive symptoms, tics, eating changes, and rare cases of psychosis or mania.
- Reported prevalence varies widely due to differences in definitions, sampling methods, confirmation of infection, severity of acute illness, and length of follow-up.
- Multiple mechanisms may contribute, including immune and inflammatory signaling, changes in blood-brain barrier permeability, autonomic dysfunction, and altered brain metabolism. Pandemic-related stressors likely contribute more to certain neuropsychiatric presentations.
- Most symptoms improve over time, but some children experience persistent symptoms for months, resulting in significant functional impairment.
Defining Pediatric Long COVID and the Challenges of Inconsistent Criteria
No universally accepted definition of pediatric long COVID exists. Some research definitions require at least one persistent physical symptom lasting more than 12 weeks after confirmed infection, not attributable to another diagnosis. Clinical guidelines often use broader criteria, including symptoms persisting from 4 weeks onward. This lack of standardization leads to conflicting prevalence estimates and complicates comparison of studies or translation of findings to clinical practice. Understanding how long COVID is defined in each study is essential before applying its conclusions.
How SARS-CoV-2 may affect the nervous system
Neurological and neuropsychiatric symptoms likely arise through multiple pathways that vary by individual and symptom cluster. Proposed contributors include systemic inflammation and immune activation after infection, changes in blood-brain barrier permeability, effects on brain immune cells, autonomic nervous system dysfunction, and altered brain energy metabolism. In children who had severe illness or required intensive care, persistent symptoms may overlap with post-intensive care syndromes rather than classic long COVID after mild infection. Similar symptoms may reflect different underlying processes, highlighting the importance of careful clinical history and contextual assessment.
Neurological symptoms reported in pediatric long COVID
Several neurological symptoms are consistently reported across studies, although prevalence estimates vary widely. Cognitive symptoms, including brain fog, attention problems, and memory difficulties, are common, especially among older children and adolescents. However, some controlled studies show similar rates in uninfected peers, emphasizing the importance of considering the broader pandemic context.
Headache is frequently reported, but prevalence estimates decrease when only controlled studies are considered. Most children experience symptom improvement over time, although some report prolonged symptoms. Fatigue is among the most common complaints, yet it is difficult to define and measure. Fatigue is likely multifactorial, with contributions from inflammation, sleep disruption, deconditioning, and psychological stress.
Smell and taste disturbances are recognized features of COVID-19 but are less common and less persistent in children than in adults. Dizziness is reported at low pooled prevalence in meta-analyses, although self-report studies sometimes describe higher rates. Seizures and encephalitis or encephalopathy are rare but significant, usually occurring during the acute phase or with multisystem inflammatory syndromes, with potential long-term consequences for survivors.
Neuropsychiatric symptoms associated with pediatric long COVID
Neuropsychiatric symptoms are frequently reported in pediatric long COVID cohorts, although establishing causation is challenging. Sleep disturbances and mood or anxiety symptoms are among the most common, especially in adolescents. Some studies show these symptoms improve over time, while others report persistence in some patients.
Reports of obsessive-compulsive symptoms, tics, eating changes, and other psychiatric presentations exist, but much of the literature is based on small studies or case reports. Many of these symptoms increased in children during the pandemic regardless of infection status. Careful interpretation and inclusion of appropriate control groups are essential when evaluating these findings.
Why prevalence estimates vary so widely
The pediatric long COVID literature is challenging to synthesize due to substantial differences in case definitions, participant recruitment, inclusion of control groups, follow-up duration, and symptom measurement. Studies in specialty clinics are especially susceptible to selection bias, while community-based studies often report lower prevalence estimates.
Practical clinical implications
Persistent neurological and mental health symptoms should be taken seriously, especially when they interfere with daily functioning, school attendance, or quality of life. Comprehensive assessment is essential, including consideration of alternative diagnoses and contributing factors. Clinical history helps differentiate post-infectious or immune-mediated patterns from deconditioning, autonomic dysfunction, or primary psychiatric conditions.
Red flags, including seizures, encephalopathy, severe functional decline, or significant psychiatric risk, warrant early referral. Psychoeducation for families and schools is essential, as symptoms may be genuine and impairing even when routine testing does not reveal abnormalities.
From a systems and research perspective, larger pediatric cohorts, extended follow-up, better-controlled study designs, and clearer identification of risk and protective factors are needed. Elucidating underlying mechanisms is essential to move from observation to targeted interventions.
Article highlights
- Children and adolescents usually have mild acute COVID-19 but can develop persistent symptoms.
- Long COVID in youth can involve neurological and neuropsychiatric symptoms, including headache, fatigue, cognitive difficulties, smell or taste changes, dizziness, mood symptoms, and sleep problems.
- Reported prevalence and duration vary widely due to differences in study design, definitions, and follow-up.
- Infection-related mechanisms may contribute more strongly to neurological symptoms, while pandemic-related factors may contribute more to some neuropsychiatric symptoms.
- More robust pediatric research is needed to clarify mechanisms, disease course, and clinically useful screening and treatment approaches.
Gabriella True
