4. What are possible inflammatory heart diseases related with COVID-19 in the paediatric age group?

4. What are possible inflammatory heart diseases related with COVID-19 in the paediatric age group?

In the frame of the actual COVID-19 pandemic, an increasing number of children being admitted for clinical symptoms of a multisystem inflammatory syndrome in children (MIS-C) have been observed. These reports came specifically from countries with a high number of COVID-19 infections, as Italy, Spain, United Kingdom and the United States. An association to a COVID-19 infection or a secondary reaction is questioned, but there is a growing concern that the symptoms are caused by a SARS-CoV-2 related inflammatory reaction.

At the moment, clinical observations and collected data do not allow a clear correlation of the inflammatory syndrome to a COVID-19 triggered cause. The serology for SARS-CoV-2 can be positive or negative.

Severe courses of COVID-19 infections in the pediatric age group are in general rare. The described severe cases present not first line with pulmonary symptoms but with an untypical inflammatory reaction and gastrointestinal complaints. The cardiovascular system is affected by a vasculitis and in some cases by myocardial dysfunction. The clinical presentation shows overlapping features of a toxic shock syndrome and Kawasaki syndrome (or atypical one), but criteria for the Kawasaki disease do not apply fully for diagnosis.

Both inflammatory syndromes seem to be based on an increased inflammatory reaction with associated vasculitis.

Some patients are described of having presented with a refractory vasodilatory shock syndrome with a normal cardiac function. In rare cases, children can present with a septic or cardiogenic shock with impaired cardiac function (mainly LV).

Different organizations as the WHO, the CDC and the RCPCH published a definition of the MIS-C which vary slightly from each other. [18,17,22]

Main clinical symptoms for the MIS-C in children are:

• fever of > 38,5°C (≥ 2 days)
• rash, lymphadenopathy, sore throat, headache, myalgia, vomiting, conjunctivitis, abdominal symptoms
• blood test: signs of inflammation with elevated CRP and neutrophilia
• organs dysfunction (≥ 2):
• Heart (vasculitis, myocardial dysfunction, hypotonia)
• Lung
• Kidney
• Gastrointentinal
• CNS
• Skin lesions
• Exclusion of
• other infections (sepsis, bacterial shock syndromes)
• myocarditis as primary origin

Positive for current or recent SARS-CoV2 infection by PCR, serology or antigen test or covid 19 contact within 4 weeks prior to onset of symptoms.

Recommended diagnostic at admission:

• Blood counts, electrolytes, BGA, lactate, liver and renal parameters, coagulation parameters, D-Dimers, fibrinogen, AT III, FVIII, vW-Antigen, bleeding time, CRP, procalcitonin, IL-6, ferritin, soluble IL-2-receptor, CK, CK-MB, myoglobin, troponin-I/-T, pro-BNP, triglycerides, C3, C4, C3d (id available), haptoglobin, immunoglobulines IgG, IgA, IgM, IgE; eventually: ANA, ANCA 
• SARS-CoV-2 Serology 
• Urine: routine stix, otherwise electrolytes, protein, myoglobin and microbiology 
• Virology: nasopharyngeal swab for SARS-CoV-2 and RT-PCR 
• Bacteriology: blood cultures 
• Echocardiography: visualization of the coronary arteries, LV function, if needed: myocardial biopsy 
• Sonography abdomen

Important differences in findings between Kawasaki disease and MIS-C:

• Kawasaki has neutrophilic myocarditis, MIS-C lymphocytic myocarditis
• elevated troponin and pro-BNP is seen in MIS-C (not seen in Kawasaki)
• Kawasaki has high platelets (not seen in MIS-C)
• lower albumin and coagulation disturbances (increased d-dimers) in MIS-C
• IL-6 and ferritin elevated in MIS-C (not seen in Kawasaki)
• lymphopenia in MIS-C (not seen in Kawasaki)

Treatment of the MIS-C:

• vasculitis: steroids, IVIG and aspirin
• shock: inotropes, management of cardiac dysfunction
• possibly IL-6 inhibitors

The etiology is not yet conclusive and might be in accordance to the inflammatory reaction seen with a delay in adults. As related to the results of genetic analysis in Kawasaki research, the origin of the inflammation might be associated to genes that regulate the rate of production of T-cell or antibody responses or the clearing of antibody and immune complexes. [18,17,22]