Multisystem inflammatory syndrome in children (MIS-C) is a severe complication associated with SARS-CoV-2 infection that frequently affects the cardiovascular system. Although acute cardiac abnormalities usually resolve, the long-term cardiovascular consequences of MIS-C remain uncertain. Previous follow-up of this cohort 2 years after MIS-C identified signs of subclinical cardiovascular abnormalities compared with healthy controls.

This cross-sectional study aims to evaluate cardiovascular health in individuals 5 years after MIS-C. Participants with a history of MIS-C will be compared with age- and sex-matched healthy controls using cardiovascular imaging, vascular assessments, cardiopulmonary exercise testing, and biomarkers of endothelial injury.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe hyperinflammatory condition associated with SARS-CoV-2 infection. Cardiovascular involvement is common during the acute phase of the disease and may include myocardial dysfunction, arrhythmias, hypotension, and coronary artery abnormalities. Although most patients experience rapid clinical recovery following immunomodulatory treatment, the long-term cardiovascular consequences of MIS-C remain incompletely understood.

The investigators previously evaluated cardiovascular health approximately 2 years after MIS-C and found evidence of subclinical cardiovascular abnormalities, including higher blood pressure values, increased concentrations of biomarkers associated with endothelial injury, and increased carotid intima-media thickness compared with healthy controls. These findings suggested that vascular changes may persist beyond the acute phase of the disease.

The aim of the present study is to assess cardiovascular health 5 years after MIS-C and to determine whether cardiovascular abnormalities remain detectable in long-term follow-up.

This is a cross-sectional study with a healthy control group. The MIS-C group will consist of individuals who were hospitalized with MIS-C at the Department of Pediatrics of the Medical University of Warsaw Children's Clinical Hospital between October 2020 and February 2021. Healthy controls will be recruited from primary care clinics and matched to the MIS-C group by age and sex.

All participants will undergo a comprehensive cardiovascular evaluation including:

• laboratory testing (complete blood count, fasting glucose, HbA1c, lipid profile);
• assessment of endothelial injury biomarkers, including galectin-3, soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble intercellular adhesion molecule-1 (sICAM-1);
• arterial stiffness assessment using pulse wave analysis and pulse wave velocity measurements;
• carotid intima-media thickness (cIMT) ultrasound;
• transthoracic echocardiography;
• cardiopulmonary exercise testing on a cycle ergometer.

The primary outcome is aortic (central) systolic blood pressure. Secondary outcomes include peripheral blood pressure, vascular stiffness parameters, carotid intima-media thickness, echocardiographic parameters, cardiopulmonary exercise test results, and concentrations of galectin-3, sICAM-1, and sVCAM-1. Outcomes will be compared between participants with a history of MIS-C and healthy controls to determine whether subclinical cardiovascular abnormalities persist 5 years after MIS-C.

The study is expected to provide important information regarding the long-term cardiovascular health of post-MIS-C patients and may help identify individuals who could benefit from ongoing cardiovascular surveillance.

Inclusion Criteria:

• For the MIS-C group: History of MIS-C diagnosed according to World Health Organization (WHO) criteria
• For all participants: Written informed consent from a parent or legal guardian and, where applicable, assent/consent from participants aged 16 years or older /

Exclusion Criteria:

MIS-C group:

1. Known heart disease, including congenital heart disease.
2. Significant chronic disease affecting growth, development, or daily functioning.

Control group:

1. Elimination diet.
2. Competitive athletic training.
3. Known heart disease, including congenital heart disease.
4. Significant chronic disease affecting growth, development, or daily functioning.

Study Population

MIS-C group: Individuals hospitalized at the Children's Clinical Hospital of the Medical University of Warsaw with a diagnosis of multisystem inflammatory syndrome in children (MIS-C) between October 2020 and February 2021.

Control group: Healthy age- and sex-matched individuals recruited from primary care clinics in Warsaw.