Long-term Neurological and Psychological Outcomes in Children and Adolescents with MIS-C


Multisystem inflammatory syndrome in children (MIS-C) has emerged as a concerning condition associated with SARS-CoV-2 infection, primarily affecting children and adolescents.

As our understanding of this condition continues to evolve, it has become increasingly important to investigate its long-term effects on the neurological and psychological well-being of affected individuals. In this cohort study, we delve into the outcomes experienced by children and adolescents with MIS-C six to twelve months after hospitalization, comparing them with both a sibling control group and a community control group.

This comprehensive analysis aims to shed light on the potential neurological and psychological sequelae that may affect executive functioning, internalizing symptoms, quality of life, and fatigue in this population.

Study Design

The strength of this study lies in its meticulous approach to assessing cognitive and psychological health outcomes in children and adolescents post-MIS-C. Unlike previous research, this study directly evaluates cognition and relies on parent-reported psychological health assessments.

Furthermore, it utilizes a contemporaneously assessed control group, predominantly consisting of siblings, who share a similar genetic and sociodemographic background as the MIS-C cases. This design not only improves the specificity of the findings but also allows us to distinguish between adverse psychological consequences associated with the COVID-19 pandemic, such as disruptions in education and lifestyle changes, and those specifically related to MIS-C.

Comparative Findings

When comparing the MIS-C group to the control groups, several noteworthy trends emerge. While the cognitive assessments reveal comparable scores between the groups, the MIS-C cohort exhibits a higher prevalence of neurological abnormalities, worsened working memory performance, and increased behavioral symptoms, with a particular emphasis on somatization and depression.

The quality of life, especially in terms of psychosocial health, appears to be significantly lower in the MIS-C group. Fatigue is also more commonly reported among individuals with MIS-C. It is essential to emphasize that abnormal neurological examination findings at follow-up do not appear to be associated with adverse psychological outcomes.

These findings underscore the complexity of MIS-C as a condition, highlighting the potential for both neurological and psychological impacts in the long term. Notably, these outcomes extend beyond the acute phase of the illness, indicating that children and adolescents may continue to experience significant challenges in the months following hospitalization.

Comparison with Previous Studies

To provide context for these findings, it is crucial to compare them with earlier research in this area.

Two prior clinic-based studies directly assessed neurological outcomes in children following MIS-C, with Penner et al. reporting a 39% rate of abnormal neurological examination findings six months post-hospitalization, compared to 25% in this study.

Several factors may account for this discrepancy, such as variations in SARS-CoV-2 variants, earlier recognition of MIS-C, relaxation of pandemic restrictions, or advancements in treatment.

A Dutch study of children hospitalized in the ICU for MIS-C found normal intelligence but increased emotional problems and lower quality of life than population norms four months after hospitalization, aligning with the findings of this study. These consistent patterns suggest that even with easing pandemic restrictions, children with MIS-C may face enduring challenges in terms of psychological well-being and quality of life.

Potential Physiological Mechanisms

Understanding the potential physiological mechanisms behind the observed outcomes is critical. MIS-C is characterized by severe inflammation and hematologic abnormalities, which may promote thrombosis, hemorrhage, and other neurological insults.

Hemodynamic compromise is associated with an increased risk of cerebral ischemia or stroke, while the use of steroids in treatment may have adverse behavioral effects. Surprisingly, many hospitalization-related variables, such as the length of stay, shock, CPR, ECMO, inflammation, or steroids, were not found to be significantly associated with neurobehavioral outcomes in this study.

However, lower left ventricular ejection fraction (LVEF) and ICU admission did show a significant association with worse executive functioning, suggesting potential links between the hyperinflammatory process and brain and heart function. Further research is needed to confirm these preliminary findings and delve into the underlying mechanisms.

Complexities of Post-ICU Syndrome

The study also touches upon the concept of Post-Intensive Care Unit Syndrome in Pediatrics, a multifaceted constellation of cognitive, physical, and mental health impairments that may occur after ICU admission. This syndrome underscores the interconnectedness of various domains, such as cognition, family dynamics, and psychological health, in medically complex populations like children with MIS-C. This interconnectedness highlights the need for a holistic approach to assessment and intervention for these patients.

Overlap with Post-acute Sequelae of COVID-19

Intriguingly, the psychological profile observed in the MIS-C cases in this study exhibits significant overlap with reported post-acute sequelae of COVID-19. Symptoms such as “brain fog,” depression, and poor sleep have been associated with post-COVID-19 conditions. While the pathophysiological processes are not yet fully understood, potential mechanisms include neuroinflammation, deconditioning, autonomic disturbances, and posttraumatic stress. The similarities between the psychological profiles of MIS-C cases and post-COVID-19 individuals suggest the possibility of common underlying mechanisms, warranting further exploration.


This cohort study sheds light on the long-term neurological and psychological outcomes in children and adolescents following MIS-C, providing critical insights into the challenges faced by this population. While cognitive assessments reveal comparability with control groups, the MIS-C cohort exhibits a higher prevalence of neurological abnormalities, worsened working memory performance, and increased behavioral symptoms. Quality of life, especially psychosocial health, is notably lower in the MIS-C group, and fatigue is more common.

These findings emphasize the importance of ongoing monitoring and support for children and adolescents who have experienced MIS-C. Additionally, they underscore the need for further research into the physiological mechanisms underlying these outcomes, as well as their potential overlap with post-acute sequelae of COVID-19. By comprehensively understanding the long-term effects of MIS-C, we can better tailor interventions and support systems to improve the overall well-being of affected individuals.

in deep …

Multisystem Inflammatory Syndrome in Children (MIS-C): A Comprehensive Overview

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but serious medical condition that emerged during the COVID-19 pandemic. This condition primarily affects children and adolescents and is characterized by severe inflammation in various organ systems.

MIS-C has raised significant concerns among healthcare professionals and parents due to its potentially life-threatening nature. In this comprehensive article, we will delve into the various aspects of MIS-C, including its clinical presentation, diagnostic criteria, underlying causes, treatment options, and long-term implications.

Clinical Presentation


MIS-C can present with a wide range of symptoms, making it challenging to diagnose. Common symptoms include:

  • Fever: Persistent high fever is a hallmark of MIS-C.
  • Gastrointestinal Symptoms: Abdominal pain, vomiting, and diarrhea.
  • Cardiovascular Symptoms: Chest pain, rapid heartbeat, and low blood pressure.
  • Skin Rash: Skin may become red, swollen, or develop a rash.
  • Conjunctivitis: Redness and inflammation of the eyes.
  • Neurological Symptoms: Headache, confusion, and irritability.
  • Respiratory Symptoms: Shortness of breath and cough.

Organ Involvement

MIS-C can affect multiple organ systems, including the heart, lungs, gastrointestinal tract, skin, and nervous system. Cardiac involvement is particularly concerning and can lead to conditions like myocarditis.

Diagnostic Criteria

Diagnosing MIS-C involves a combination of clinical evaluation and laboratory tests. The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have established criteria for diagnosis, which include:

  • Age less than 21 years.
  • Fever for at least 24 hours.
  • Laboratory evidence of inflammation (elevated C-reactive protein, erythrocyte sedimentation rate, or procalcitonin).
  • Evidence of organ dysfunction, such as cardiac, renal, respiratory, or gastrointestinal involvement.
  • No alternative plausible diagnosis.

Underlying Causes

MIS-C is believed to be an immune response triggered by a previous SARS-CoV-2 infection, even if the initial COVID-19 infection was asymptomatic. Several theories regarding the underlying causes of MIS-C include:

  • Immune Dysregulation: It is thought that the body’s immune response goes into overdrive, leading to widespread inflammation.
  • Molecular Mimicry: Some experts suggest that the virus may trigger an autoimmune response by mimicking human proteins, leading to immune system confusion.
  • Genetic Factors: Genetic predisposition may play a role in why some children develop MIS-C while others do not.

Treatment Options

The management of MIS-C typically involves a multidisciplinary approach that includes pediatricians, infectious disease specialists, and cardiologists. Treatment strategies may include:

  • Intravenous Immunoglobulin (IVIG): IVIG is a common treatment to reduce inflammation and modulate the immune response.
  • Corticosteroids: Steroids like dexamethasone can be used to manage severe inflammation.
  • Supportive Care: Patients may require intensive care for cardiac or respiratory support.
  • Anticoagulants: In some cases, anticoagulants may be prescribed to prevent blood clots.
  • Monitoring: Continuous monitoring of vital signs and organ function is crucial.

Long-term Implications

MIS-C is associated with significant morbidity and mortality, but many children recover with prompt treatment. However, there are potential long-term implications to consider:

  • Cardiac Issues: Some children may develop long-lasting heart problems, including cardiomyopathy and arrhythmias.
  • Neurological Complications: Persistent neurological symptoms or cognitive impairments can occur.
  • Psychological Impact: The experience of severe illness can have psychological effects on children.

Prevention and Future Research

Preventing MIS-C primarily involves preventing COVID-19 infections in children. Vaccination against COVID-19 has shown promise in reducing the risk of both the initial infection and MIS-C. Continued research is essential to better understand the pathogenesis of MIS-C and to develop targeted treatments.


Multisystem Inflammatory Syndrome in Children is a complex and potentially life-threatening condition associated with COVID-19. While it remains rare, healthcare professionals and parents should be vigilant about its symptoms and seek prompt medical attention when necessary. Advances in research and healthcare practices will continue to improve our understanding and management of this challenging syndrome, ultimately ensuring the well-being of our children during the COVID-19 pandemic and beyond.

reference link : https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2807432


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