New COVID-19-Related Syndrome in Children Raises Concerns

As the first wave of the COVID-19 pandemic begins to subside in parts of the United States, doctors around the country and especially in hard-hit New York City are reporting cases of an apparently related inflammatory syndrome. Initially termed “pediatric multisystem inflammatory syndrome” and subsequently renamed “multisystem inflammatory syndrome in children” (MIS-C) by the CDC, the new disorder already has affected more than 100 children in the city alone. At least dozens of other children have been affected in the rest of the United States and abroad.

The condition, though relatively rare, can appear in children of all ages, from toddlers to teens—essentially, the same group that seems to naturally resist infections with the SARS-CoV-2 virus that causes COVID-19. It is thought to be, for the most part, not an infectious disease but a “post-infection syndrome” arising as a delayed, inflammatory response after a minor or asymptomatic infection with the coronavirus has cleared.

MIS-C has been largely treatable, and so far, the vast majority of patients have recovered. But several children, including at least three in New York State and one in the United Kingdom, have died of it, and the sudden surge of cases of this potentially serious illness has doctors and parents concerned.

“Initially it had seemed that COVID-19 posed a significant threat only to adults, but with this syndrome, the worries over its effects on children are rising,” said Dr. Karen Acker, a pediatric infectious disease specialist who is an assistant professor of clinical pediatrics at Weill Cornell Medicine.

What MIS-C looks like

The precise mechanisms underlying MIS-C are so far unclear, and there may be some overlap with the storm of inflammation seen in many adult patients with active COVID-19 infection. However, many doctors suspect that MIS-C is at least partly an autoimmune condition, in which antibodies or T-cells that are part of the immune response to the virus end up attacking the child’s own tissues—a phenomenon known to occur in other post-infection autoimmune syndromes.

Children with MIS-C usually run a moderate to high fever for a few days, and often have abdominal pain, with or without diarrhea, as well as muscle aches, some form of rash, and conjunctivitis (or pink eye). They may also have swollen lymph nodes, and swollen hands and feet. But they generally do not have COVID-19-like respiratory symptoms, said Dr. Acker, who is also an assistant attending pediatrician at NewYork-Presbyterian Komansky Children’s Hospital.

Although children with this new syndrome may not seem especially unwell when they arrive at the hospital, tests will often reveal high levels of inflammation in various parts of the body including the blood vessels, heart, and kidneys. Especially if it goes untreated, this inflammation can lead to life-threatening complications such as abnormal dilations of coronary arteries, kidney injuries, and blood clots. Some children experience a steep drop in blood pressure, which in turn can lead to dangerous reductions in blood circulation, threatening organ failure. The one child reported to have died of MIS-C in the United Kingdom, a 14-year old boy, developed this “hyperinflammatory shock” condition and died after large blood clots formed in his cerebral arteries.

Connection to COVID-19

Physicians are treating MIS-C as a COVID-19-related illness, Dr. Acker said. Though rare compared to COVID-19 itself, MIS-C has appeared suddenly amid the pandemic and with an incidence far above what would be expected if it were a post-infection syndrome triggered by other pathogens. Moreover, a large proportion of children with MIS-C have tested positive for antibodies to the COVID-19 coronavirus, or less commonly, for the coronavirus’s genetic material—a sign of an active or very recent infection.

Predisposing factors

report in the medical journal The Lancet on a cluster of eight cases at a South London medical center in April noted that six of the affected children, including one who died, were of Afro-Caribbean background. Seven of the eight were overweight—the 14-year-old who died had a BMI of 33, which is considered obese. However, those few cases may have reflected mainly the demographics of the area served by the medical center, rather than an association with risk of MIS-C. In general, there have been so few clinical reports to date that doctors don’t know why some children with COVID-19 exposure develop this inflammatory syndrome while the vast majority do not.

“It’s too early to tell—doctors are seeing patients from multiple ethnic backgrounds that appear to mimic the ethnic disparities seen in adults with COVID-19,” Dr. Acker said. “Some are obese and some are not; most have no prior medical history.”

Resemblance to Kawasaki disease

The signs and symptoms of MIS-C usually overlap to some extent with those of Kawasaki disease, an inflammatory syndrome that was first described in Japan in the 1960s and typically affects a few thousand children in the United States every year. Kawasaki disease is suspected of being a post-infection syndrome because it sometimes occurs in community clusters and has a winter-spring seasonality, but it has never been conclusively tied to a particular pathogen.

Although MIS-C cases tend to look similar to Kawasaki disease in many respects, there seems to be more variability in children’s symptoms, and MIS-C affects a much broader age range compared to Kawasaki disease, which usually affects only children under five.

MIS-C also somewhat resembles toxic-shock syndrome, in which bacterial toxins induce hyperinflammation, leading to multi-organ complications and dangerous drops in blood pressure. Although toxic shock syndrome is a distinct ailment, some of its inflammatory mechanisms may be the same ones active in MIS-C cases with severe low blood pressure.


MIS-C’s close resemblance to Kawasaki disease has led doctors to treat it in a similar way. The established treatment for Kawasaki disease is an immune-quieting combination of high-dose aspirin and intravenous immunoglobulin (IVIG)—essentially human antibodies from donated blood, which include antibodies that can powerfully reduce inflammation. Some doctors are following that practice for MIS-C patients, while others are de-emphasizing aspirin, using it only in low doses to help prevent blood clots, because they are also using steroids to prevent or treat the type of heart inflammation that often arises in patients. (IVIG is being investigated separately as a potential treatment for acute COVID-19.)

Children with MIS-C who develop severe low blood pressure may be sent to an intensive care unit to receive extra support, possibly including breathing support, although MIS-C is not considered a respiratory illness.

“For the most part, kids with this syndrome do very well, and even if they go to the ICU they usually are out in a matter of days, unlike most of the adult COVID-19 cases we see,” Dr. Acker says.

In cases of Kawasaki disease, heart inflammation can lead to long-term heart abnormalities including aneurysms and valve defects. Pediatric cardiologists are monitoring children who have recovered from MIS-C to see if similar problems develop.

Key unanswered questions

“We’d really like to know why some children get MIS-C and most don’t; what treatments are optimal; and what long-term outcomes we can expect for these kids, especially cardiac outcomes,” Dr. Acker said. Research into the precise cause and mechanisms of MIS-C also is likely to inform the understanding of Kawasaki disease and other post-infection syndromes.

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