In April and May 2020, reports of children experiencing symptoms related to Kawasaki syndrome gained prominence in U.S. media. Referred to as multisystem inflammatory system in children (MIS-C), at least one hundred sixty-one children were identified as having the ailment in the United States, and three have died.1 MIS-C was particularly concerning due to its apparent nature as a post-COVID-19 response in populations thought to be largely unaffected by the disease. But what exactly is MIS-C and how much do we know about it?
Children experience mysterious symptoms related to Kawasaki syndrome. What is MIS-C? And how is it related to COVID-19?
Although the cause of MIS-C is currently not understood, the symptoms that the syndrome induces appear to include inflammation of “the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs,” according to the U.S. Centers for Disease Control (CDC).2 It is important to note, though, that these findings are preliminary and that more research is required to ascertain any other effects in children that may be adverse to their health. The CDC also noted that there is currently little understanding as to whether children with undetermined pre-existing conditions are more prone to contracting the syndrome.2
MIS-C: New Syndrome
The medical community’s current understanding from MIS-C can largely be derived from studies published in scientific journals over the past month that examined children with the syndrome. One study from The Lancet examined children with symptoms suggesting MIS-C in Bergamo province, one of Italy’s hardest hit and located northeast of the city of Milan.3 It is important to note, though, that this study occurred before the name of the new syndrome – MIS-C – was established.
MIS-C: Children experiencing symptoms related to Kawasaki syndrome
The Bergamo study found that the symptoms in these children were comparable to that of Kawasaki syndrome, but that there were some minor differences in recorded data when compared to children that were naturally affected by Kawasaki syndrome.3
Research Reports on MIS-C related to COVID-19
The study noted that compared to natural incidences of the syndrome, the number of patients experiencing Kawasaki syndrome had increased significantly, from zero to three incidences per month to ten per month, suggesting that the increase in incidence was related to the COVID-19 pandemic in northern Italy.3 Additionally, the mean age of those affected had increased, from predominantly zero to three years of age to five to seven years of age.3 Cardiac involvement was also at a much higher rate than natural incidences, as was macrophage activation syndrome (MAS), and the need for adjunctive steroid treatment, which is typically used for patients exhibiting septic shock.3
Symptoms of MIS-C and COVID-19 Abnormalities
Cardiac involvement, which can cause “diastolic dysfunction, congestive heart failure (CHF), severe ventricular arrhythmia and atrioventricular conduction abnormalities,” has also been noted in patients testing positive for COVID-19.4
With regard to MAS, according to The Rheumatologist, Kawasaki syndrome is marked by circulatory dysfunction and MAS, or unregulated activation and expansion of T lymphocytes and histiocytes.5 The proliferation of these lymphocytes and histiocytes is thus disconcerting, particularly because MAS can lead “to a massive systemic inflammatory response” where “reported mortality rates reach 20-30%.”5
Similarly, a study in southeast England showed that in the majority of children exhibiting symptoms, no pathological organism was identified, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19).6 Five of eight patients in the study tested negative for the virus, with only two testing positive and one testing positive for a different virus altogether, an adenovirus.6
Of the eight patients, all but one exhibited diarrhoea; five of eight experienced abdominal pain; four of eight experienced a rash; three of eight experienced odynophagia; five of eight experienced conjunctivitis; other symptoms experienced amongst the group included headache and myalgia, though these were both less common.6 Regardless, all eight patients required some form of organ support, most commonly mechanical ventilation via endotracheal tube (MV) or non-invasive ventilation.6
Most Severe Patient Case of MIS-C
The most severe instance of MIS-C manifested in a fourteen-year-old male who required MV, as well as renal replacement therapy and veno-arterial extracorporeal membrane oxygenation, suggesting significant damage or failure of the kidneys and respiratory system, respectively.6 All patients were given a lengthy drug cocktail, but for the fourteen-year-old male, imaging results showed that despite limited adverse health effects in other patients, his were most profuse.6
Imaging results indicated inflammation of the intestines (ileitis), gallbladder edema, ascites (excess abdominal fluid), and basal lung consolidations, suggesting the buildup of liquid in the lungs inhibiting respiratory function for the fourteen-year-old male.6 The male passed away after six days, with an ischaemic infarction, or stroke, being designated as the cause for significant deterioration of his health.6
This England study, conducted at Evelina London Children’s Hospital, was one of the first studies to analyze the symptoms, treatments, and outcomes of children affected by MIS-C and to share such data with the pediatric community.6 However, there are additional concerns that MIS-C may not be a phenomenon isolated to children, and that it can also affect young adults, another segment of the population previously believed to be largely unaffected by COVID-19.
Young Adults Are Also Affected by MIS-C and COVID-19
Across the United States, although the majority of MIS-C patients have been younger children, there have also been young adults in their early-to-mid 20s exhibiting symptoms of MIS-C of greater intensity than children.7 Many physicians’ concerns regarding MIS-C in young adults is that physicians for this age demographic are likely less familiar with Kawasaki syndrome as it is typically most prevalent in younger populations, which could contribute to an underdiagnosis of MIS-C when compared to that in pediatric communities.7
Similar to their younger counterparts, though, young adults exhibiting MIS-C have tested positive for COVID-19 antibodies, providing renewed evidence that the syndrome can be a post-immune response to the disease.7 The reasons for which certain individuals may be predisposed to MIS-C are currently not understood, and an investigation by the New York State Department of Health is working to determine whether there exists any genetic links between those with the syndrome that can lead to a better understanding of MIS-C in the medical community.7
Altogether, little is currently known about MIS-C; the cause of its counterpart, Kawasaki disease, is also not well understood in the medical community. However, it is apparent that populations once conceived of as not being affected by COVID-19 can potentially be vulnerable. The rate at which patients with MIS-C deteriorate, as well as the incidences of necessitation of organ support, have been alarming for the medical community.
Further Research on MIS-C
Further research will be required to ascertain which drug cocktails are particularly potent in inhibiting the extreme immune response younger people have exhibited in response to MIS-C, as well as to determine whether certain individuals in this population are more prone to developing the syndrome.
- Goldstein, Joseph, and Jesse McKinley. “After 3 Children Die, a Race to Investigate a Baffling Virus Syndrome.” The New York Times, The New York Times, 22 May 2020, http://www.nytimes.com/2020/05/22/nyregion/children-coronavirus-syndrome-new-york.html.
- “For Parents: Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 20 May 2020, http://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/children/mis-c.html.
- Verdoni, Lucio, et al. “An Outbreak of Severe Kawasaki-like Disease at the Italian Epicentre of the SARS-CoV-2 Epidemic: an Observational Cohort Study.” The Lancet, 2020, doi:10.1016/s0140-6736(20)31103-x.
- Tahir, Faryal, et al. “Cardiac Manifestations of Coronavirus Disease 2019 (COVID-19): A Comprehensive Review.” Cureus, 2020, doi:10.7759/cureus.8021.
- “Macrophage Activation Syndrome.” The Rheumatologist, 19 June 2016, http://www.the-rheumatologist.org/article/macrophage-activation-syndrome/.
- Riphagen, Shelley, et al. “Hyperinflammatory Shock in Children during COVID-19 Pandemic.” The Lancet, vol. 395, no. 10237, 2020, pp. 1607–1608., doi:10.1016/s0140-6736(20)31094-1.
- Ariana Eunjung Cha, Chelsea Janes. “Young Adults Are Also Affected by Kawasaki-like Disease Linked to Coronavirus, Doctors Say.” The Washington Post, WP Company, 21 May 2020, http://www.washingtonpost.com/health/2020/05/21/misc-c-kawasaki-coronavirus-young-adults/.
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