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As data continue to emerge about a multi-system inflammatory disorder in children apparently connected to COVID-19, evidence is growing that this is not your typical Kawasaki disease.

In New York, , and three children have died from it in the state as of Wednesday. Other cases have been reported in Washington, California, and elsewhere in the U.S. as well as in Europe.

Children with Kawasaki disease also develop fever, red eyes and rash, but this new inflammatory syndrome differs in terms of presentation in a number of ways, said Nadine Choueiter, MD, of The Children's Hospital at Montefiore in New York City, which has seen .

"Children are coming in critically ill, with fever and abdominal pain, vomiting and in shock," she told MedPage Today.

In fact, shock -- in which patients need medication to maintain blood pressure and intensive care unit treatment -- may be the critical differentiator between this and traditional Kawasaki disease. Choueiter noted fewer than 5% of patients with Kawasaki disease present with shock.

"Markers of inflammation are massively elevated" with the new syndrome, she said. These patients also have low lymphocyte counts, whereas traditional Kawasaki disease comes with a high count.

Treatment for the two conditions also differs, Choueiter said, as patients with Kawasaki disease are generally treated with intravenous immunoglobulin.

However, if patients don't meet the case definition of Kawasaki disease, Choueiter said they are trying to treat "the inflamed organ," such as the heart or the kidneys, with anti-inflammatory medications that are only used in a minority of patients with Kawasaki disease.

Unlike COVID-19, where pre-existing conditions seem to play a role in severity of infection, Choueiter said most children presenting with this syndrome were previously healthy, and "most were not aware they had COVID."

"Some had a positive PCR test, some had a negative PCR test. Among the negative tests, some had a positive test for antibodies, which suggests they were exposed to the virus weeks back," she noted.

Choueiter noted kids can be hospitalized in the ICU for 1 to 2 weeks for this syndrome, or in less serious cases, a few days.

"So far, most who have been admitted have gone home," she said.

This emerging syndrome has also caught the attention of the federal government. At a press briefing on Monday, Adm. Brett Giroir, MD, a White House coronavirus task force member and Health and Human Services (HHS) assistant secretary, was asked about it. He responded that "CDC is interacting with a pediatric ICU network to ."

The Assistant Secretary for Preparedness and Response is also looking at special treatments, he said, and noted the "activation of all branches of HHS working with networks at children's hospitals."

"It's a small percentage, but can be quite frightening," said Giroir, who is a pediatric critical care specialist. "It is serious and can be a fatal condition."

Choueiter said the CDC developing a case definition would ensure all centers seeing these patients would have a uniform approach to the condition. A management plan would also be helpful, she added.

"It's a good first step, so we can identify patients, triage them and figure out how to manage them," Choueiter noted.

Meanwhile, the American Heart Association's Young Hearts Council adopted the , which doesn't require a positive PCR test for SARS-CoV-2.

Emerging Data

Published data on the new syndrome have largely come from Europe. Italian researchers reported Wednesday in The Lancet on a series of 10 children who were diagnosed with the Kawasaki-like syndrome after the outbreak of COVID-19 illness there from Feb. 18 to April 20, 2020 -- in the number of cases compared to the 19 total children with Kawasaki disease in the previous 5 years.

Researchers led by Lorenzo D'Antiga, MD, of Ospedale Papa Giovanni XXIII in Bergamo, Italy, found these most recent 10 children were older (mean age around 8 vs around 4 years), with a higher rate of cardiac involvement, Kawasaki disease shock syndrome and macrophage activation syndrome and all of the most recent cases needed high-dose cortical steroids.

Seven boys and three girls were admitted, on average, on day 6 of fever.

Notably, while half of patients presented with classic Kawasaki disease, the other half presented with an "incomplete" form of the disease. Eight of the 10 children were positive for antibodies to SARS-CoV-2 (IgG or IgM or both). Still, they differed from the historical cohort of patients with Kawasaki disease, the authors said.

"From a clinical perspective, they were older, had respiratory and gastrointestinal involvement, meningeal signs, and signs of cardiovascular involvement," they wrote, "From a biochemical perspective, they had leucopenia with marked lymphopenia, thrombocytopenia, and increased ferritin, as well as markers of myocarditis."

The authors also noted that in the past 20 years, coronaviruses "have been proposed as possibly implicated in the pathogenesis of Kawasaki disease."

An accompanying editorial by Russell Viner, PhD, of UCL Great Ormond Street Institute of Child Health, London, and Elizabeth Whittaker, PhD, of Imperial College London discussed the .

"For prospective studies, measuring antibody at the time of presentation, as well as consenting patients for appropriate research samples, will be essential to elucidate the mechanism of this syndrome," they wrote. "If this is an antibody-mediated phenomenon, there might be implications for vaccine studies, and this might also explain why some children become very ill with COVID-19, while the majority are unaffected or asymptomatic."

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