DIAGNOSIS AND MANAGEMENT OF COVID-19 INFECTION
IN CHILDREN

Sri Lanka College of Paediatricians, Family Health Bureau and

World Health Organisation (WHO)- Sri Lanka

8 Multisystem Inflammatory Syndrome In Children Temporally Associated With COVID – 19 (MIS-C)

Multisystem Inflammatory Syndrome in children is observed at a rising trend in children with or without COVID-19 status. The exact mechanism of disease pathophysiology is not well understood but suggested to result from a dysregulated immune response leading to a massive cytokine storm like Kawasaki disease or Macrophage Activation Syndrome. Please note: A single definite guideline for case definition and management does not exist at present.

8.1 Clinical manifestations and case definitions 
Understanding of the spectrum of the disease and clinical sub-phenotypes is evolving.

COVID-19-associated MIS-C
Febrile, inflammatory state Kawasaki Disease like illness Severe MIS-C
Some children may present with persistent fevers and mild symptoms (viz. headache, fatigue). Inflammatory markers may be elevated, but signs of severe multisystem involvement are lacking. Some children meet the criteria for complete or incomplete Kawasaki Disease and do not develop shock and severe multisystem involvement. Children with severe MIS-C have markedly elevated inflammatory markers and severe multisystem involvement. Cardiac involvement and shock are common.
8.2 Case definition as per WHO guidelines, May 2020
Children and adolescents 0–19 years of age with fever > 3 days
AND
Two of the following:
  • Rash or bilateral non-purulent conjunctivitis or mucocutaneous inflammation signs (oral, hands, or feet).
  • Hypotension or shock.
  • Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin),
  • Evidence of coagulopathy (by PT, PTT, elevated d-Dimers).
  • Acute gastrointestinal problems (diarrhea, vomiting, or abdominal pain).
AND
  • Elevated markers of inflammation such as ESR, C-reactive protein, or procalcitonin.
AND
  • No other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes.
AND
  • Evidence of COVID-19 (RT-PCR, antigen test, or serology positive) or likely contact with patients with COVID-19.


8.3 Management of MIS-C
MIS-C is a life-threatening condition, and patients may need medical care at a pediatric intensive care unit (PICU) under the close supervision of pediatric intensivists. There is no consensus on the specific and optimal treatment, but standard algorithms may guide initial medical management.
  • Monitor for clinical signs of worsening inflammation such as worsening fever, cardiorespiratory deterioration, worsening gastrointestinal symptoms, increasing hepatosplenomegaly or lymphadenopathy, extending rash, worsening neurological symptoms, laboratory signs of increasing inflammation, falling blood cell counts, rising ferritin, unexpectedly low or falling ESR, rising fibrinogen or new-onset low fibrinogen, rising ALT, AST or LDH, rising triglycerides, rising D-dimers, low serum sodium with worsening renal function
  • Look for multisystem involvement (liver, renal, neurological, etc.)
  • Consider IVIG and aspirin early if they fulfill the criteria for Kawasaki Disease.
  • Consider IVIG if it fulfills criteria for toxic shock syndrome
  • All cases with suspected myocardial involvement (elevated troponin I / ECG change and/or ECHO abnormalities) should be transferred to a cardiac center with continuous infectious disease/immunology input.
Treatment arms are directed by the presence or absence of cardiac dysfunction, shock, coronary involvement, or multi organs dysfunction.
  • In the presence of the above features: Methylprednisolone 1 to 2 mg/kg per day AND intravenous Immunoglobulin 2 g/kg over 24 to 48 hours.
 
  • In the absence of cardiac dysfunction, shock, coronary involvement, multi organs dysfunction: Methylprednisolone 1 to 2 mg/kg per day OR intravenous Immunoglobulin 2 g/kg over 24 to 48 hours (depends on availability/feasibility).
 
  • If the child does not improve with the above treatment or deteriorates, options include:
    • Repeat IVIg
    • High dose corticosteroid (methylprednisolone 10 to 30 mg/kg/day for 3 to 5 days)
    • Aspirin: 3 mg/kg/day to 5 mg/kg/day max 81 mg/day (if thrombosis or Coronary Aneurysm Score is >2.5)
    • Low Molecular Weight Heparin: Enoxaparin: 1 mg/kg twice daily subcutaneously. Clotting factor Xa should be between 0.5 to 1 (if patient has thrombosis/ Coronary aneurysm score > 10 or LVEF < 30%)
  Steroids need to be tapered over 2 to 3 weeks while monitoring inflammatory markers. For children with cardiac involvement, repeat ECG 48 hourly, repeat ECHO at 7 to 14 days and between 4 to 6 weeks, and at one year if initial ECHO was abnormal.   Biological agents: different biological agents have been used as more targeted therapy against the widespread inflammation like Anakinra, an IL1 receptor antagonist, or Tocilizumab, an anti-IL6, or scarcely infliximab, an anti-TNFα agent in the severe spectrum of disease.