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Public health surveillance for multisystem inflammatory syndrome in children (MIS-C) affirmed the distinctive constellation of symptoms, but case definitions may belie a larger burden of less clear disease.

Among the 99 cases reported to the by May 10, all presented with fever or chills, 97% had tachycardia, 80% had gastrointestinal (GI) symptoms, 60% had rash, 56% had red eyes, and 27% had mucosal changes.

Among the 186 cases in 26 states with targeted surveillance by the national study reported by Manish Patel, MD, of the CDC in Atlanta, and colleagues, organ system involvement was GI in 92%, mucocutaneous in 75%, and respiratory in 70%.

Cardiac involvement was common in both studies: In , 80% had cardiovascular involvement, 48% received vasoactive support, and 8% of the children had coronary artery aneurysms documented with z scores ≥2.5.

In the New York data reported by Elizabeth Dufort, MD, of its Department of Public Health in Albany:

• 62% needed vasopressors
• 52% had ventricular dysfunction
• 32% had pericardial effusion
• 9% had documented coronary artery aneurysm (seven of the nine were diagnosed with Kawasaki's disease)
• 36% had a diagnosis of myocarditis, and another 16% had clinical myocarditis

Fully 80% of cases as defined by the CDC required ICU support and 2% died in these two studies done in conjunction with the CDC and published in the New England Journal of Medicine.

"Overall, a consistent clinical picture is emerging," said Michael Levin, PhD, of Imperial College London, in an .

These larger cohorts mostly confirm prior findings on the the affected age range (median 8-10 years, but range from infants to late teens), predominance of Hispanic/black children affected, presenting symptoms (GI symptoms are frequent), and that cardiac involvement is common, noted Kevin Friedman, MD, of Boston Children's Hospital and a member of the American Heart Association's Young Hearts Council and its Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee.

However, Levin drew attention to the issue of case definitions.

The of "pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2" (PIMS) released in April was followed by a narrower released in May by the CDC and WHO for MIS-C.

These "hastily developed case definitions based on the most severe cases" might miss less serious cases, Levin noted. For example, the CDC and WHO definitions require evidence of SARS-CoV-2 infection or exposure, which "is problematic, since asymptomatic infections are common and antibody testing is neither universally available nor reliable."

Children meeting MIS-C diagnostic criteria could represent the "tip of the iceberg," Levin wrote.

Notably, coronary artery aneurysms have occurred across the umbrella of PIMS cases: the critically ill, those meeting diagnostic criteria for Kawasaki's disease, and some patients with unexplained fever and inflammation, he pointed out.

In the New York State surveillance data, there were 191 potential MIS-C cases reported by hospitals in the state.

Of them, 95 were confirmed cases based on laboratory evidence of elevated levels of two or more inflammatory markers and a positive molecular test for SARS-CoV-2 or antibodies against the virus detected within 10 days after admission.

Another four with suspected MIS-C, based on clinical evidence and exposure to a person with COVID-19 in the 6 weeks before hospitalization, had similar characteristics to the confirmed cases.

Whether the rest of the iceberg -- children with self-resolving inflammation never seen for MIS-C -- is still at risk for aneurysms, and what cardiac follow-up they might need warrants studies involving not only the patients whose condition meets the current definitions, but also those with unexplained fever and inflammation, Levin argued.

"Indeed, the case definitions may need refinement to capture the wider spectrum of illness," he wrote.

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