Clinical Overview of Multisystem Inflammatory Syndrome in Children

At a glance

  • MIS-C is a rare but serious complication that may begin weeks after a child is infected with SARS-CoV-2, the virus that causes COVID-19.
  • The child may have been infected from an asymptomatic contact, and, in some cases, the child and their caregivers may not even know they had been infected.
  • COVID-19 vaccination is effective at reducing the risk of MIS-C.
Three health care providers discussing interventions

Signs and symptoms

MIS-C symptoms may begin weeks after a child is infected with SARS-CoV-2. The child may have been infected from an asymptomatic contact, and, in some cases, the child and their caregivers may not even know they had been infected. Not all children will have the same signs and symptoms of MIS-C, and some children may have signs and symptoms not listed here.

  • Patients with MIS-C usually present with fever and some combination of abdominal pain, vomiting, diarrhea, skin rash, and mucocutaneous lesions (i.e., conjunctivitis). In severe cases, children can present with low blood pressure and shock.
  • Patients with MIS-C have elevated laboratory markers of inflammation (e.g., C-reactive protein, ferritin); many have laboratory markers indicating damage to the heart (e.g., elevated troponin), and many have low platelet or absolute lymphocyte counts (thrombocytopenia and lymphopenia, respectively).123
  • Some patients with MIS-C develop cardiac dysfunction (e.g., decreased left ventricular function) and coronary artery dilatation or aneurysm.124
  • Gastrointestinal inflammation can manifest as abdominal pain, vomiting, and diarrhea; children may have signs and symptoms similar to those of acute appendicitis.5
  • Neck pain has also been described, sometimes with development of retropharyngeal edema or phlegmon on radiographic imaging.6
  • Patients with MIS-C can also have neurologic involvement which is usually transient and presents as headache or altered mental status. 78
  • Other severe neurologic manifestations may include encephalopathy, stroke, and demyelination. Fulminant cerebral edema may also occur, although this is rare.78

Reducing risk

MIS-C and vaccination

Parents of children ages 6 months - 17 years should discuss COVID-19 vaccination with a healthcare provider.91011

Multiple studies have found that COVID-19 vaccination is effective at reducing the risk of MIS-C, with one CDC study finding that two doses of Pfizer-BioNTech COVID-19 vaccine had a greater than 90% estimated effectiveness at preventing MIS-C.12

CDC has also created Considerations for Initiating COVID-19 vaccination in people with a history of MIS-C.

For Everyone How to Protect Yourself and Others

Resources

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Content Source:
National Center for Immunization and Respiratory Diseases; Coronavirus and Other Respiratory Viruses Division (CORVD)
  1. Yousaf AR, Lindsey KN, Wu MJ, et al. Notes from the Field: Surveillance for Multisystem Inflammatory Syndrome in Children — United States, 2023. MMWR Morb Mortal Wkly Rep 2024;73:225–228. DOI: http://dx.doi.org/10.15585/mmwr.mm7310a2
  2. Miller AD, Yousaf AR, Bornstein E, et al. Multisystem Inflammatory Syndrome in Children During Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta and Omicron Variant Circulation-United States, July 2021-January 2022. Clin Infect Dis. Oct 3 2022;75(Supplement_2):S303-S307. doi:10.1093/cid/ciac471
  3. Miller AD, Zambrano LD, Yousaf AR, et al. Multisystem Inflammatory Syndrome in Children-United States, February 2020-July 2021. Clin Infect Dis. Aug 24 2022;75(1):e1165-e1175. doi:10.1093/cid/ciab1007
  4. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. May 23 2020;395(10237):1607-1608. doi: 10.1016/S0140-6736(20)31094-1
  5. Valitutti F, Verde A, Pepe A, et al. Multisystem inflammatory syndrome in children. An emerging clinical challenge for pediatric surgeons in the COVID 19 era. J Pediatr Surg Case Rep. Jun 2021;69:101838. doi:10.1016/j.epsc.2021.101838
  6. Jenkins E, Sherry W, Smith AGC, et al. Retropharyngeal Edema and Neck Pain in Multisystem Inflammatory Syndrome in Children (MIS-c). J Pediatric Infect Dis Soc. Oct 27 2021;10(9):922-925. doi:10.1093/jpids/piab050
  7. LaRovere KL, Poussaint TY, Young CC, et al. Changes in Distribution of Severe Neurologic Involvement in US Pediatric Inpatients With COVID-19 or Multisystem Inflammatory Syndrome in Children in 2021 vs 2020. JAMA Neurol. Nov 7 2022; doi:10.1001/jamaneurol.2022.3881
  8. LaRovere KL, Riggs BJ, Poussaint TY, et al. Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome. JAMA Neurol. May 1 2021;78(5):536-547. doi:10.1001/jamaneurol.2021.0504
  9. Schwartz N, Ratzon R, Hazan I, et al. Multisystemic inflammatory syndrome in children and the BNT162b2 vaccine: a nationwide cohort study. Eur J Pediatr. 2024 Aug;183(8):3319-3326. doi: 10.1007/s00431-024-05586-4.
  10. Nygaard U, Holm M, Hartling UB, et al. Incidence and clinical phenotype of multisystem inflammatory syndrome in children after infection with the SARS-CoV-2 delta variant by vaccination status: a Danish nationwide prospective cohort study. Lancet Child Adolesc Health. Jul 2022;6(7):459-465. doi:10.1016/S2352-4642(22)00100-6
  11. Zambrano LD, Newhams MM, Olson SM, et al. Overcoming COVID-19 Investigators. BNT162b2 mRNA Vaccination Against Coronavirus Disease 2019 is Associated With a Decreased Likelihood of Multisystem Inflammatory Syndrome in Children Aged 5-18 Years-United States, July 2021 - April 2022. Clin Infect Dis. 2023 Feb 8;76(3):e90-e100. doi: 10.1093/cid/ciac637.
  12. Yousaf AR, Cortese MM, Taylor AW, et al. MIS-C Investigation Authorship Group. Reported cases of multisystem inflammatory syndrome in children aged 12-20 years in the USA who received a COVID-19 vaccine, December, 2020, through August, 2021: a surveillance investigation. Lancet Child Adolesc Health. 2022 May;6(5):303-312. doi: 10.1016/S2352-4642(22)00028-1.