Be Alert for MIS-C, Uncommon but Serious Inflammation in Post-COVID Kids

Whitney Kopp, MD
Providence Sacred Heart Children’s Hospital

What began as a fever for seven-year-old Harmony quickly revealed itself as something much more dangerous, a symptom of a rare pediatric condition associated with COVID-19. Not long after being admitted, doctors at Providence Sacred Heart Children’s Hospital diagnosed the young girl with multisystem inflammatory syndrome in children (MIS-C).

The complication known to appear in children after COVID-19 has become more common as the pandemic has progressed. This postinfectious condition causes different parts of the body to become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs, and exhibits features like Kawasaki, toxic shock syndrome and secondary haemophagocytic lymphohistiocytosis (HLH).1

Clinicians in the UK first identified and reported MIS-C in April 20202. Concurrent with the UK discovery, cases were reported in New York City and Italy. The cases appeared to peak about a month after the height of COVID-19 infections happening around the same time.

As of December 2021, 93 cases have been reported in Washington State. Harmony’s diagnosis is one of 11 in Spokane County.3 Thankfully, Harmony recovered from MIS-C. She reunited with her family after 12 days of care at Providence Sacred Heart Children’s Hospital in Spokane.  

Below is additional information for clinicians who may be treating pediatric COVID patients to help spread the word about this uncommon, yet dangerous condition. While we continue to learn more about COVID effects, I urge you to keep MIS-C in mind as you care for the children in our community.

The CDC defines MIS-C as follows4:

  • An individual aged <21 years presenting with fever (>38)
  • Laboratory evidence of inflammation
  • 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

Review of current MIS-C5:

  • Male predominance
  • Previously healthy
  • Median age ~ 8 years in CDC study
  • 91% with GI symptoms
  • Cardiac dysfunction common (41%), 35% shock, 23% myocarditis
  • High severity of illness (majority required ICU admission)

Lab evaluation6:

  • Evidence of inflammation, common values: CRP >3 mg/dL, ESR >40 mm/h, ferritin >500 ng/mL, ANC >7700, ALC 2 ug/mL, fibrinogen >400 mg/dL, albumin 40 U/ L, INR >1.1 • Other: AKI, hyponatremia, high LDH, high troponin, BNP >400 pg/mL, prolonged PT or PTT; If ESR low but high ferritin and CRP, consider MAS
  • ECHO, EKG and CXR

Treatment7:

  • Supportive care, transfer to higher level as care when indicated
  • Multidisciplinary team (cardiology, critical care, rheumatology, ID and hematology as needed)
  • Reasonable to start antibiotics while waiting for confirmation of diagnosis
  • IVIG (2 g/kg) and aspirin.  Some patients may meet criteria for anticoagulation
  • Steroids (low and high dose have been used especially in refractory MISC)
  • Anakinra (IL-1 receptor antagonist) or tocilizumab (IL-6 inhibitor) for refractory but discuss with rheumatology prior to starting
  • Patients should follow up with cardiology, rheumatology, etc. as recommended by specific teams

Sources and more information:

[1] Postinfectious inflammatory condition related to COVID-19 feature similar to Kawasaki, toxic shock syndrome, secondary HLH (Feldstein, L. R., Rose, E. B., Horwitz, S. M., Collins, J. P., Newhams, M. M., Son, M. B., Newburger, J. W., Kleinman, L. C., Heidemann, S. M., Martin, A. A., Singh, A. R., Li, S., Tarquinio, K. M., Jaggi, P., Oster, M. E., Zackai, S. P., Gillen, J., Ratner, A. J., Walsh, R. F., … Randolph, A. G. (2020). Multisystem inflammatory syndrome in U.S. children and adolescents. New England Journal of Medicine, 383(4), 334–346. https://doi.org/10.1056/nejmoa2021680)

[2] Pediatric Inflammatory Multi-system Syndrome – temporally associated with SARS-CoV 2 (PIMS-TS): Critical Care guidance https://pccsociety.uk/wp-content/uploads/2020/05/PIMS-TS-Critical-Care-Clinical-Guidance-v4.pdf

[3] Washington state statistics https://www.doh.wa.gov/Portals/1/Documents/1600/coronavirus/data-tables/MultisystemInflammatorySyndromeChildrenCOVID19WA2020.pdf

[4] CDC definition https://www.cdc.gov/mis/mis-c/hcp/index.html (Please check this link for the fully detailed case definition for MIS-C.)

[5] Review of current MIS-C:

  • Soma, V. L., Shust, G. F., & Ratner, A. J. (2020). Multisystem inflammatory syndrome in children. Current Opinion in Pediatrics, 33(1), 152–158. https://doi.org/10.1097/mop.0000000000000974
  • T. Radia, N. Williams, P. Agrawal et al., Multi-system inflammatory syndrome in children & adolescents (MIS-C): A systematic review of clinical features and presentation, Pediatric Respiratory Reviews, https://doi.org/10.1016/j.prrv.2020.08.001

[6] Lab evaluation:

  • Seattle Children’s Hospital, Kazmier, K., Albert, J., de la Morena, M., Eckart, C., Fenstermacher, S., Hartford, E., Hayward, K., Kemna, M., Matthews, D., Nickless, J., Nutman, S., Portman, M., Sushan, D., Valdivia, H., Vora, S., Waghmare, A., Migita, D., 2020 December. COVID-19 Pathway. Available from: https://www.seattlechildrens.org/pdf/covid-19-pathway.pdf
  • Feldstein, L. R., Rose, E. B., Horwitz, S. M., Collins, J. P., Newhams, M. M., Son, M. B., Newburger, J. W., Kleinman, L. C., Heidemann, S. M., Martin, A. A., Singh, A. R., Li, S., Tarquinio, K. M., Jaggi, P., Oster, M. E., Zackai, S. P., Gillen, J., Ratner, A. J., Walsh, R. F., … Randolph, A. G. (2020). Multisystem inflammatory syndrome in U.S. children and adolescents. New England Journal of Medicine, 383(4), 334–346. https://doi.org/10.1056/nejmoa2021680

[7] Treatment:

  • “Covid-19 (Acute COVID and Mis-C) Care – Seattle Children’sCOVID-19 Pathway v6.0: Table of Contents.” COVID-19 Pathway v6.0, https://www.seattlechildrens.org/pdf/covid-19-pathway.pdf.
  • Soma, V. L., Shust, G. F., & Ratner, A. J. (2020). Multisystem inflammatory syndrome in children. Current Opinion in Pediatrics, 33(1), 152–158. https://doi.org/10.1097/mop.0000000000000974

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