Quality of Life in Children Who Were Treated for Multisystem Inflammatory Syndrome in Children

The COVID-19 pandemic has led to high morbidity and mortality in adults. Still, in children, the clinical picture and course of the disease are generally milder, and the overall estimated mortality rate is approximately 0.08%. However, it has been observed that in children after recovering from COVID-19, regardless of the severity of the clinical picture, a severe condition may occur, characterized by an inadequate hyper-inflammatory immune response with possible repercussions on various organ systems. Ultimately, the condition was recognised as a specific clinical entity which was named Multisystem Inflammatory Syndrome in Children (MIS-C). Guidelines for diagnosing a case of MIS-C have evolved. According to the current guidelines of the American Academy of Paediatrics, the following criteria must be met: 1. An individual aged <21 years and in the absence of a more likely alternative diagnosis; 2. Subjective or documented fever (T >38.0°C); 3. Clinical course requiring hospitalisation or leading to death; 4. C-reactive protein (CRP) >3.0 mg/dL; 5. New-onset manifestations that include >2 of the following categories: a) Cardiac: coronary artery dilation/aneurysm, left ventricular ejection fraction <55%, or troponin elevated above normal; b) Shock; c) Mucocutaneous: rash, oral mucosal inflammation, conjunctivitis/conjunctival injection, or extremity findings (erythema, edema); d) Gastrointestinal: abdominal pain, vomiting, or diarrhea; e) Hematologic: platelet count <150,000/µL, absolute lymphocyte count <1000/µL. 5. Detection of SARS-CoV-2 nucleic acid/antigen up to 60 days before or during hospitalisation or in a postmortem specimen, OR detection of antibodies associated with the current illness, OR close contact with a confirmed/probable case of COVID-19 within 60 days before hospitalisation. The clinical picture is very diverse, and most often affects the gastrointestinal, respiratory, cardiocirculatory, and haematological systems, as well as the skin and mucous membranes; however, any organ or organ system can be affected.

The therapeutic approach is based on the use of organ-specific supportive and immunomodulatory therapy. Treatment guidelines recommend the use of intravenous immunoglobulins (2 g/kg), then corticosteroids (2-30 mg/kg/day methylprednisolone, depending on the severity of the disease) and finally biological therapy (most often anakinra, 2-10 mg/kg/day), with thromboprophylaxis with aspirin. Although these are mostly previously healthy children, it is described in research that even up to 80% of them required treatment in JILD, and in certain patients, it led to death. Since in a large part of these patients there is involvement of the heart, which includes ventricular dysfunction, enlargement or aneurysm of the coronary artery and arrhythmias, there is a need for longer-term follow-up due to the unclear prognosis and the risk of progression of cardiac manifestations, and in a smaller number of patients, the persistence of cardiac dysfunction has been described even six months after discharge from the hospital. Although less common, neurological manifestations are part of the clinical picture of MIS-C and carry a significant risk of chronic morbidity and mortality; Neurological sequelae and long-term neurodevelopmental outcomes are currently unknown and require further research. Longer-term follow-up of children with MIS-C is of interest. Even in cases of recovery, given the broad spectrum of the disease, its involvement of nearly all organ systems, and the variable clinical presentation, there is a need for regular and continuous follow-up and contact with medical care.

Aim and Purpose of the Research This scientific research hypothesises that children suffering from MIS-C have a worse quality of life compared to their peers, as measured by validated HRQoL questionnaires, 24 months after hospital discharge.

The second hypothesis is that the value of the PRISM III/IV and PIM-3 scores in children suffering from MIS-C correlates with the outcome and quality of life measured 24 months after hospital discharge.

Specific research objectives: