COVID-19-associated multisystem inflammatory syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Synonyms and keywords: Multisystem Inflammatory Syndrome in Children (MIS-C)

Overview

Multisystem Inflammatory Syndrome in Children (MIS-C) is a condition that causes inflammation of some parts of the body like heart, blood vessels, kidneys, digestive system, brain, skin, or eyes. According to recent evidence, it is suggested that children with MISC had antibodies against COVID-19 suggesting children had COVID-19 infection in the past. This syndrome appears to be similar in presentation to Kawasaki disease, hence also called Kawasaki -like a disease. It also shares features with staphylococcal and streptococcal toxic shock syndromes, bacterial sepsis, and macrophage activation syndromes. [1]

Epidemiology and Demographics

  • According to a recent study among the 186 children with MIS-C, the rate of hospitalization was 12% between March 16 and April 15 and 88% between April 16 and May 20.
  • 80% of the children were admitted to the intensive care unit and 20% of the children required mechanical ventilation.
  • 4% of the children required extracorporeal membrane oxygenation.
  • The mortality rate among 186 children with MIS-C was 2%.

Age

  • Among the 186 children with MIS-C distribution of age group was
    • <1yr-7%
    • 1-4yr-28%
    • 5-9yr-25%
    • 10-14yr-24%
    • 15-20yr-16%.

Gender

  • Among the 186 children with MIS-C

Comorbidities

  • Children with MIS-C had following underlying comorbidities.
    • Clinically diagnosed Obesity-8%
    • BMI-Based Obesity-29%
    • Cardiovascular diasease-3%
    • Respiratory disease-18%
    • Autoimmune disease or immunocompromising condition-5%

Organ System Involved

  • 71% of children had involvement of at least four organ systems.

The most common organ system involved in MIS-C children among a total of 183 children were.

  • Gastrointestinal(92%)
  • Cardiovascular(80%)
  • Hematologic(76%)
  • Mucocutaneous(74%)
  • Pulmonary(70%)

Pathophysiology

Symptoms

Emergency Warning Signs

Laboratory Findings

'Radiological Findings[17]

Test Findings
Chest Xray patchy symmetrical infiltrates, pleural effusion
Echocardiogram and EKG myocarditis, valvulitis, pericardial effusion, coronary artery dilatation
Abdominal USG colitis, ileitis, lymphadenopathy, ascites, hepatosplenomegaly

Diagnosis

Preliminary WHO case definition: Children and adolescents
  • 0–19 years of age with fever >3 days

AND

  • Two of the following:
  1. Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet)
  2. Hypotension or shock
  3. Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP)
  4. Evidence of coagulopathy (by PT, PTT, elevated D-Dimers)
  5. Acute gastrointestinal problems (diarrhea, vomiting, or abdominal pain)

AND

AND

AND

  • Evidence of COVID-19 (RT-PCR, antigen test or serology-positive), or likely contact with patients with COVID-19
CDC Case Definition for MIS-C[18]
  • An individual aged <21 years presenting with fever, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological);

AND

No alternative plausible diagnoses;

AND

Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.

Classification of Disease Severity of MIS-C

  • Mild Disease[19]
  • Children with MIS-C fall under this category who-
    • require minimal to no respiratory support.
    • minimal to no organ injury
    • normotensive
    • Do not meet the criteria for ICU admission.
  • Severe Disease[20]
  • Children with MIS-C fall under this category who-
    • have significant oxygen requirements (HFNC, BiPAP, mechanical ventilation).
    • have a mild-severe organ injury and ventricular dysfunction.
    • have a vasoactive requirement.
    • meet the criteria for ICU admissions.

Treatment

  • All the children with MIS-C are treated as suspected COVID-19.[21]
  • Mild to Moderate cases of MIS-C are managed supportively.
  • Supplemental oxygen is required in children with low oxygen saturation.
  • Fluid resuscitation in 10 ml/kg aliquots with reevaluation after each bolus. Maintain euvolemia. Avoid hypervolemia.
  • Anti-inflammatory treatments with Intravenous immunoglobulin(IVIG) with or without corticosteroids have shown a good response rate.[22]
  • Aspirin has been used primarily for its antiplatelet effect. It is recommended in all patients with MIS-C.[22]
  • Anakinra is considered if fevers last more than 24 hours post steroids/IVIG or in the moderate or severe presentation.[23]
  • Tocilizumab is also considered if fevers last more than 24 hours post steroids/IVIG or in the moderate or severe presentation.[24]
  • Empiric antibiotics like vancomycin, ceftriaxone, and clindamycin are given for community-acquired shock presentation until cultures are negative for 48 hours.
Prsentation Treatment
Mild Disease
  • Symptomatic Treatment
Severe Disease
  • Symptomatic Treatment
  • IVIG(IV)
  • Corticosteroids(IV/PO)
  • Consider adding Anakinra or Tocilizumamb if fever persist for more than 24 hours post steroids and IVIG use.

Prevention of MIS-C

  • MIS-C can be prevented by reducing the risk of child exposure to COVID-19 infection.

Complications of MIS-C

References

  1. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  2. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  3. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  4. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  5. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  6. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  7. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  8. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  9. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  10. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  11. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  12. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  13. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  14. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  15. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  16. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  17. <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf >
  18. <"Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C) | CDC".>
  19. <https://www.chkd.org/uploadedFiles/Documents/COVID-19/CHKD%20MIS-C%20Guideline%20D2.pdf |title=www.chkd.org |format= |work= |accessdate=>
  20. <https://www.chkd.org/uploadedFiles/Documents/COVID-19/CHKD%20MIS-C%20Guideline%20D2.pdf |title=www.chkd.org |format= |work= |accessdate=>
  21. <"www.rcpch.ac.uk" (PDF).>
  22. 22.0 22.1 Rajapakse, Nipunie; Dixit, Devika (2020). "Human and novel coronavirus infections in children: a review". Paediatrics and International Child Health: 1–20. doi:10.1080/20469047.2020.1781356. ISSN 2046-9047.
  23. <https://www.chkd.org/uploadedFiles/Documents/COVID-19/CHKD%20MIS-C%20Guideline%20D2.pdf |title=www.chkd.org |format= |work= |accessdate=>
  24. <https://www.chkd.org/uploadedFiles/Documents/COVID-19/CHKD%20MIS-C%20Guideline%20D2.pdf |title=www.chkd.org |format= |work= |accessdate=>