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MIS-C: The Impact of COVID-19 on the Pediatric Population

By: Erica Tonti, PharmD Candidate c/o 2022

Multisystem Inflammatory Syndrome in Children, or MIS-C, is a recent syndrome recognized by the Centers for Disease Control and Prevention (CDC). The emergent outbreak of COVID-19 brought concern as to who would be affected by MIS-C and how severe the impact of the syndrome would be. Children, thought to be somewhat immune from this virus, were deemed to be free from inclusion of the “at-risk” category.

             As of April 2020, MIS-C was a growing concern amongst children’s hospitals in both the United States and the United Kingdom. While MIS-C may be rare, it is imperative that signs and symptoms are acknowledged in order to treat it before any long-term damage is observed. MIS-C is a condition where organs and tissues, such as the heart, lungs, blood vessels, kidneys, skin, brain, and digestive system become severely inflamed. This inflammation can cause a constriction of blood flow and may lead to damage of multiple organ systems, ranging from aneurysms in the coronary arteries to severe inflammation that can impair the functioning ability of the heart.2

According to the CDC guidelines, the diagnosis of MIS-C is seen in patients under the age of 21 years old, most commonly between the ages of 2 and 15, that presents with a persistent fever of 100.4°F and evidence of organ dysfunction including cardiac, renal, respiratory, or neurological involvement.7 The inflammatory nature of this syndrome also requires that a child suspected of MIS-C must have evidence of inflammation in the form of an elevated C-reactive protein, d-dimer protein fragment, the presence of elevated neutrophils, or low albumin levels.7 This syndrome can develop within four weeks of exposure to COVID-19, so identification of a positive diagnosis will ensure that the symptoms are due to MIS-C.

Although the cause is not yet fully understood, researchers believe that this syndrome is caused by a delayed immune response to the coronavirus that exceeds the typical response, causing an immense amount of inflammation that can progress into organ damage.2 A recent study explained that serum levels express elevated levels of two specific immune system molecules which could be producing an enhanced immune response to the coronavirus. Kevan Herold, MD, Professor of Immunology and Internal Medicine at Yale University, along with Betsy Herold, MD, Professor of Pediatrics and Microbiology-Immunology at Albert Einstein College of Medicine, studied blood samples of children who were admitted to the Montefiore Medical Center with symptoms of COVID-19. In this cohort were adolescent patients that were diagnosed with MIS-C. They discovered that the levels of interleukin 17A (IL-17A), which plays a key role in mobilizing the immune system during the early stages of an infection, and interferon gamma (INFγ) which counters viral replication, were higher in younger patients. The upregulation of systemic inflammatory cytokines is similar to other “cytokine storms” activating both innate and adaptive immune cells. This extensive inflammatory reaction in these MIS-C patients led to tissue damage, resulting in activation of T cells and autoantibodies which were among the potential reasons for the occurrence of MIS-C.4

Since MIS-C is a relatively new syndrome, the symptoms vary among patients. Kawasaki disease is an illness that correlates with many of the symptoms that are seen in MIS-C. This illness is characterized by inflammation of the blood vessels, damaging the coronary arteries and limiting the oxygen supply to the heart. These symptoms include the presence of a rash, bloodshot eyes, a swollen tongue, and enlarged lymph nodes in the neck. Another syndrome that is closely related to MIS-C is Toxic Shock Syndrome, which is a complication associated with bacterial infections due to toxins produced by Staphylococcus aureus. These symptoms include high fever, a sunburn-like rash, and hypotension. Other symptoms associated with MIS-C include diarrhea, abdominal pain, or respiratory problems that have been reported with COVID-19 such as persistent cough or shortness of breath.6 

Early detection of MIS-C is essential for achieving the most effective results of treatment. The key to treating these patients is to control the inflammation to avoid any long-term organ damage. The three classes of medications utilized for the treatment of MIS-C include anticoagulating agents, IV immunoglobulin, and anti-inflammatory drugs. Low dose aspirin at a dose of 3-5mg/kg/day is also commonly used in treatment. If there is decreased left ventricular ejection fraction, patients should be receiving enoxaparin as an anticoagulating agent.8 High dose intravenous immunoglobulin (1-2g/kg) may be another treatment option, given the patient has proper fluid administration and appropriate cardiac function. In the event that MIS-C is refractory to intravenous immunoglobulins, anakinra (Kineret), which is another immunosuppressive agent, may be considered to treat these patients. As observed in adult patients diagnosed with COVID-19, respiratory symptoms are most commonly reported. Anakinra, at a dose of 4mg/kg/day is first-line therapy for immunomodulatory treatment in children with hyper-inflammation in association with a COVID-19 diagnosis.8 As with other medications in the pediatric setting, weight-based dosing should be utilized. A patient weighing less than 30kg requires a dose of 12mg/kg IV. A patient weighing more than 30kg requires a dose of 8mg/kg IV.8 Regardless of the regimen chosen, the patient is at the center of this critical decision and therapy must be optimized accordingly.

Although rare, MIS-C is dangerous if untreated in the pediatric population. MIS-C is quite a new discovery, and while its causes are still mainly unknown it is important to be aware of the signs and symptoms associated with this syndrome in order to effectively treat and maintain organ function. Prevention of exposure to COVID-19 is imperative in preventing the escalation to the symptoms correlated with Multisystem Inflammatory Syndrome in Children.


  1. Multisystem inflammatory syndrome in children (MIS-C) and COVID-19. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/mis-c-in-kids-covid-19/symptoms-causes/syc-20502550. Published 2020.
  2. Multisystem Inflammatory Syndrome in Children (MIS-C). Boston Children’s Hospital. https://www.childrenshospital.org/conditions-and-treatments/conditions/m/mis-c. Published 09/02/2020. Published 2020.
  3. Hathaway B. Children’s immune response more effective against COVID-19. YaleNews. https://news.yale.edu/2020/09/21/childrens-immune-response-more-effective-against-covid-19. Published 09/21/2020.
  4. Brodsky NN, Ramaswamy A, Lucas CL. The Mystery of MIS-C Post-SARS-CoV-2 Infection. Trends Microbiol. 2020;28(12): 956-958. doi:10.1016/j.tim.2020.10.004. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556780/
  5. Kawasaki Disease. Boston Children’s Hospital. https://www.childrenshospital.org/conditions-and-treatments/conditions/k/kawasaki-disease.
  6. Ross A, Shoff HW. Toxic Shock Syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing; November 19, 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459345
  7. Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C). Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/mis-c/hcp/. Published 08/28/2020.
  8. Henderson LA, Canna SW, Friedman KG, et al. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 1. Arthritis Rheumatol. 2020. doi: 10.1002/art.41454.
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