Multisystem inflammatory syndrome in children

Paediatric multisystem inflammatory syndrome (PMIS/PIMS/PIMS-TS)
Other names
  • Multisystem inflammatory syndrome in children (MIS-C)[1]
  • Multisystem inflammatory syndrome (MIS) in children and adolescents temporally related to COVID-19[2]
  • Paediatric inflammatory multisystem syndrome (PIMS), temporally associated with SARS-CoV-2 infection (PIMS-TS)[3]
  • Kawa-COVID-19[4]
  • Systemic Inflammatory Syndrome in COVID-19 (SISCoV)[5]
TEM image of SARS-CoV-2, the coronavirus responsible for COVID-19:
PMIS / MIS-C is thought to be caused by an unusual biological response to infection in certain children
SpecialtyPaediatrics
SymptomsFever, abdominal pain, diarrhoea/vomiting, low blood pressure, insufficient blood supply (shock), pink eye, "strawberry tongue", rashes, large lymph nodes, swollen hands/feet, neurological disturbances, among others
ComplicationsCardiac dysfunction; coronary artery abnormalities, including aneurysms; acute kidney injury; coagulopathy
Usual onsettypically 2–6 weeks[6] after COVID-19 exposure
CausesSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Diagnostic methodClinical evaluation by specialists
Differential diagnosisAlternative infectious/non-infectious causes, Kawasaki disease
TreatmentIntravenous immunoglobulin (IVIG); corticosteroids; oxygen, supportive care
PrognosisResponse to treatment, generally good; long-term prognosis, unclear[7]
FrequencyRare
Deaths<2% of reported cases

Multisystem inflammatory syndrome in children (MIS-C), or paediatric inflammatory multisystem syndrome (PIMS / PIMS-TS), or systemic inflammatory syndrome in COVID-19 (SISCoV), is a rare systemic illness involving persistent fever and extreme inflammation following exposure to SARS-CoV-2, the virus responsible for COVID-19.[7] Studies suggest that MIS-C occurred in 31.6 out of 100,000 people under 21 who were infected with COVID-19.[8][9] MIS-C has also been monitored as a potential, rare[10] pediatric adverse event following COVID-19 vaccination.[11] Research suggests that COVID-19 vaccination lowers the risk of MIS-C, and in cases where symptoms develop after vaccine, is likely extremely rare or related to factors like recent exposure to COVID-19.[12] It can rapidly lead to medical emergencies such as insufficient blood flow around the body (a condition known as shock).[7] Failure of one or more organs can occur.[13] A warning sign is unexplained persistent fever with severe symptoms following exposure to COVID-19.[14] Prompt referral to paediatric specialists is essential, and families need to seek urgent medical assistance.[7] Most affected children will need intensive care.[7]

All affected children have persistent fever.[7] Other clinical features vary.[14] The first symptoms often include acute abdominal pain with diarrhoea or vomiting.[7] Muscle pain and general tiredness are frequent,[7] and low blood pressure is also common.[15] Symptoms can also include pink eye, rashes, enlarged lymph nodes, swollen hands and feet, and "strawberry tongue".[6] Various mental disturbances are possible.[6] A cytokine storm may take place,[16] in which the child's innate immune system stages an excessive and uncontrolled inflammatory response.[17] Heart failure is common.[15] Clinical complications can include damage to the heart muscle, respiratory distress, acute kidney injury, and increased blood coagulation.[18] Coronary artery abnormalities can develop (ranging from dilatation to aneurysms).[6]

This life-threatening disease has proved fatal in under 2% of reported cases.[7] Early recognition and prompt specialist attention are essential.[19] Anti-inflammatory treatments have been used, with good responses being recorded for intravenous immunoglobulin (IVIG), with or without corticosteroids.[20] Oxygen is often needed.[7] Supportive care is key for treating clinical complications.[18] Most children who receive expert hospital care survive.[7]

Knowledge of this newly described syndrome is evolving rapidly.[21] Its clinical features may appear somewhat similar to Kawasaki disease, a rare disease of unknown origin that typically affects young children, in which blood vessels become inflamed throughout the body.[15] It can also show features of other serious inflammatory conditions of childhood, including toxic shock and macrophage activation syndromes.[15] Nevertheless, it appears to be a separate syndrome.[22] Older children tend to be affected.[23]

This emerging condition has been defined slightly differently (using different names), by the World Health Organization (WHO),[24] the Royal College of Paediatrics and Child Health (RCPCH),[13] and the Centers for Disease Control and Prevention (CDC).[1] Although the condition is thought to follow SARS-CoV-2 viral infection, antigen or antibody tests are not always positive.[3] Exclusion of alternative causes, including bacterial and other infections, is essential for differential diagnosis.[3] Some general clinical guidance has been provided by the RCPCH,[13] the National Institutes of Health,[23] the American College of Rheumatology,[25] and the American Academy of Pediatrics.[26]

Clusters of new cases have been reported two to six weeks after local peaks in viral transmission.[6] The disease is thought to be driven by a delayed biological mechanism in certain predisposed children.[20] The European Centre for Disease Prevention and Control (ECDC) has rated risk to children in Europe as being 'low' overall, based on a 'very low' likelihood of a child developing this 'high impact' disease.[3] Regarding ethnicity, the condition seems to affect more children of African, Afro-Caribbean, and Hispanic descent, whereas Kawasaki disease affects more of East Asian ancestry.[19] Initial reports regarded children in various parts of Europe and the United States, and it was unclear to what extent the condition had gone unrecognized elsewhere.[24] Reports have since emerged of cases in various other countries around the world.[27][28] In adults, a similar condition has occasionally been reported, which has been called multisystem inflammatory syndrome in adults (MIS-A).[29]

  1. ^ a b Cite error: The named reference CDC2020 was invoked but never defined (see the help page).
  2. ^ "Case Report Form for suspected cases of multisystem inflammatory syndrome (MIS) in children and adolescents temporally related to COVID-19". www.who.int. World Health Organization. Archived from the original on 24 June 2020.
  3. ^ a b c d "Rapid risk assessment: Paediatric inflammatory multisystem syndrome and SARS-CoV-2 infection in children" (PDF). European Centre for Disease Prevention and Control. 15 May 2020. Archived from the original on 15 May 2020.
  4. ^ Cite error: The named reference Pouletty2020 was invoked but never defined (see the help page).
  5. ^ Dhar D, Dey T, Samim MM, et al. (2021). "Systemic inflammatory syndrome in COVID-19-SISCoV study: systematic review and meta-analysis". Pediatric Research. 91 (6): 1334–1349. doi:10.1038/s41390-021-01545-z. PMC 8128982. PMID 34006982.
  6. ^ a b c d e Cite error: The named reference ACR1 was invoked but never defined (see the help page).
  7. ^ a b c d e f g h i j k Cite error: The named reference Ahmed2020 was invoked but never defined (see the help page).
  8. ^ "Multisystem Inflammatory Syndrome in Children (MIS-C): Information for Healthcare Providers About Talking with Families and Caregivers". Centers for Disease Control. Retrieved 3 June 2024.
  9. ^ Payne, Amanda B.; Gilani, Zunera; Godfred-Cato, Shana (2021). "Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2". JAMA Netw Open. doi:10.1001/jamanetworkopen.2021.16420. PMC 8193431.
  10. ^ Zhang M, Zhang P, Liang Y, et al. (2022). "A systematic review of current status and challenges of vaccinating children against SARS-CoV-2". Journal of Infection and Public Health. 15 (11): 1212–1224. doi:10.1016/j.jiph.2022.10.006. PMC 9557115. PMID 36257126.
  11. ^ "Adverse Events Following Immunization (AEFIs) for COVID-19 in Ontario: December 13, 2020 to January 30, 2022" (PDF). Public Health Ontario. Retrieved 11 February 2022.
  12. ^ Jain, Eisha; Donowitz, Jeffrey R.; Aarons, Elizabeth; Marshall, Beth C.; Miller, Michael P. (May 2022). "Multisystem Inflammatory Syndrome in Children after SARS-CoV-2 Vaccination". Emerging Infectious Diseases. 28 (5): 990–993. doi:10.3201/eid2805.212418. PMC 9045439. PMID 35275051.
  13. ^ a b c "Guidance - Paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS)". RCPCH. Royal College of Paediatrics and Child Health. May 2020. Archived from the original on 16 June 2020.
  14. ^ a b Cite error: The named reference AAP-interim was invoked but never defined (see the help page).
  15. ^ a b c d Cite error: The named reference Sperotto2020 was invoked but never defined (see the help page).
  16. ^ Cite error: The named reference Rowley2020 was invoked but never defined (see the help page).
  17. ^ Cite error: The named reference Alunno2020 was invoked but never defined (see the help page).
  18. ^ a b Cite error: The named reference Aronoff2020 was invoked but never defined (see the help page).
  19. ^ a b Cite error: The named reference ACRdraft was invoked but never defined (see the help page).
  20. ^ a b Cite error: The named reference Rajapakse2020 was invoked but never defined (see the help page).
  21. ^ Cite error: The named reference WNY2020 was invoked but never defined (see the help page).
  22. ^ Cite error: The named reference Abrams2020 was invoked but never defined (see the help page).
  23. ^ a b Cite error: The named reference NIHchildren was invoked but never defined (see the help page).
  24. ^ a b Cite error: The named reference WHO2020 was invoked but never defined (see the help page).
  25. ^ Cite error: The named reference Pond2020 was invoked but never defined (see the help page).
  26. ^ Hester, M (21 July 2020). "AAP issues interim guidance for MIS-C". Contemporary Pediatrics. Archived from the original on 21 July 2020.
  27. ^ Cite error: The named reference Jiang2020 was invoked but never defined (see the help page).
  28. ^ Cite error: The named reference Ulloa2020 was invoked but never defined (see the help page).
  29. ^ Cite error: The named reference Morris2020 was invoked but never defined (see the help page).