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Disclosures: Cennimo and Shulman report no relevant financial disclosures.
May 15, 2020
5 min read

‘This is something new’: Syndrome associated with COVID-19 sickens more kids

Disclosures: Cennimo and Shulman report no relevant financial disclosures.
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Stanford T. Shulman
David Cennimo

As of Thursday, New York said it was investigating 110 cases and three deaths among children experiencing a syndrome that has features similar to atypical Kawasaki disease and toxic shock syndrome. New York Governor Andrew M. Cuomo has said that 60% of children with the syndrome tested positive for SARS-CoV-2 infection, and the other 40% had antibodies specific to the coronavirus, which causes COVID-19.

Similar cases have been reported in other states and countries. Physicians and media outlets, including Healio, have referred to the illness as Kawasaki-like. But most infectious disease specialists believe the syndrome is “a different entity,” said Infectious Diseases in Children Editorial Board Member Stanford T. Shulman, MD, a physician specializing in Kawasaki disease at Lurie Children’s Hospital of Chicago.

“Some of them have a few Kawasaki-like features like red eyes or rash. But they have many, many more characteristics different from Kawasaki disease than they do similarly to Kawasaki disease,” Shulman told Healio.

New York has called the illness pediatric multi-system inflammatory syndrome. The CDC, in a health alert issued to clinicians on Thursday, named it multisystem inflammatory syndrome in children (MIS-C) and said it was associated with COVID-19.

The CDC alert included a recommendation that clinicians report any cases to local, state and territorial health departments. It included a case definition for MIS-C:

  • An individual aged younger than 21 years presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (at least two) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); and
  • No alternative plausible diagnoses; and
  • Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms.

Shulman said age and race are two identifiable factors that show the illness is different from Kawasaki disease. He said 50% of all patients with Kawasaki disease are aged younger than 2 years, and 80% of patients are aged younger than 5 years. Currently, the average age of patients presenting with the newly identified illness is 10 years, he said.

Rates of Kawasaki disease are highest among Asians, but the new syndrome has not been seen in Asia, and patients in the U.S. and United Kingdom have been predominantly of African descent, Shulman said.

David Cennimo, MD, a clinician and assistant professor of adult infectious diseases at Rutgers New Jersey Medical School, agreed that the illness does not seem to be consistent with Kawasaki disease.


“I'm starting to wonder if we're making it more confusing by calling it Kawasaki-like,” Cennimo told Healio. “Kawasaki disease has a pretty stereotypical presentation. Generally, kids are 1 to 5 years old [with] high fever, inflamed lips, swollen hands, and a concern about cardiac involvement. That is typical Kawasaki disease. From what I am reading about these questionably COVID-19-associated cases, there's a lot of inflammation, but I think it's even more widespread than the typical Kawasaki disease, which has a medium-sized artery inflammation or vasculitis.”

According to Shulman, most children are presenting with fever, which is common in Kawasaki disease cases. But children are also presenting with bad abdominal pain, diarrhea and vomiting, which is very uncommon in Kawasaki disease, Shulman said. A high proportion of patients have developed shock, he said.

“That's a characteristic of a very small minority of children with Kawasaki disease,” Shulman said. “Shock is really the hallmark of the serious parts of this new syndrome.”

Shulman said laboratory tests from patients with the new syndrome “are quite different, with features that are really almost never seen in Kawasaki disease — high ferritin level; extremely high BNP values, which relates to cardiac heart issues,” he said. “So, in my mind, there are a lot more differences than there are similarities to Kawasaki disease. I think this is something new.”

Delayed reaction?

Typically, patients presenting with the new syndrome have either been infected with SARS-CoV-2 or have had antibodies to it in their system.

In a study published this week in The Lancet about an outbreak of patients presenting with Kawasaki-like disease in the Italian province of Bergamo, researchers reported that eight of 10 patients diagnosed with Kawasaki-like disease since the start of the Italian COVID-19 epidemic were positive for SARS-CoV-2 antibodies.

Just two tested positive for a current infection.

“This finding and the positivity of [immunoglobulin G] antibodies suggest a late onset of the disease compared with the primary infection, due to the host immune response,” the researchers wrote. “This might be the reason why, in the past, no active viral infection could be shown in this disease. All these results and considerations support the hypothesis that the immune response to SARS-CoV-2 is responsible for a Kawasaki-like disease in susceptible patients.”

The results “implicate a delayed reaction,” Cennimo said.

Shulman agreed. Recently, he learned of an 18-year-old patient who had a typical adult mild case of COVID-19. After recovering from the SARS-CoV-2 infection, he returned 4 or 5 weeks later presenting with the symptoms of this new syndrome.


“It does seem like there is a delay between the time when the SARS-CoV-2 virus is peaking in a community,” Shulman said. “That does not seem to be when these kinds of patients with a new syndrome are presenting; they are actually presenting more like 4 to 6 weeks later.”

Can adults get it?

In the state of New York, the average age of children with the novel syndrome has been 5 to 14 years, but it is possible that young adults could develop MIS-C. Throughout Shulman’s career as an expert on Kawasaki disease, he said he has seen only three or four adults with the disease.

“I think that spillovers into other age groups can occur, or it would not surprise me if it occurred, but it should be exceptionally rare,” Shulman said.

Cennimo said adults may have an atypical version of the disease.

“I don't think there's any reason to think that it would be impossible in adults. It's probably less likely just because we haven't seen it. But I don't think it's impossible,” Cennimo said.

Shulman said most patients are being treated with IV immunoglobulin, a standard treatment for Kawasaki disease or toxic shock syndrome.

“Patients who are being treated with IVIg, with or without steroids for the new syndrome, seem to get better,” Shulman said. “Now, we don't know whether it's because they're getting that medication or because they're just getting over the infection with all kinds of intensive support. But the good news is a very large majority of these patients are going home.”– by Ken Downey Jr.


CDC Health Alert Network. Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). Accessed May 15, 2020.

Verdoni L, et al. Lancet. 2020;doi:10.1016/S0140-6736(20)31103-X

Disclosures: Cennimo and Shulman report no relevant financial disclosures.