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COVID-19 Resource Center

Perspective from David Cennimo, MD
Disclosures: Levin reports no relevant financial disclosures. Please see the studies for all other authors relevant financial disclosures.
June 29, 2020
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‘Tip of the iceberg’: Reports detail hundreds of cases pediatric illness linked to COVID-19

Perspective from David Cennimo, MD
Disclosures: Levin reports no relevant financial disclosures. Please see the studies for all other authors relevant financial disclosures.
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Two new studies published in The New England Journal of Medicine described hundreds of cases of multisystem inflammatory syndrome in children, or MIS-C, a new disorder associated with SARS-CoV-2, the virus that causes COVID-19.

The studies detailed the epidemiology and clinical course of MIS-C among 377 patients in the United States aged 21 years or younger, including 191 in New York. Globally, around 1,000 cases of the illness have been reported, noted Michael Levin, FMedSci, PhD, professor of pediatrics and international child health at Imperial College London.

Dufort EM, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa2021756. & Feldstein LR, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa2021680.
Dufort EM, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa2021756. & Feldstein LR, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa2021680.

“Overall, a consistent clinical picture is emerging,” Levin wrote in a related editorial. “MIS-C occurs 2 to 4 weeks after infection with SARS-CoV-2. The disorder is uncommon” — occurring in just 2 in 100,000 people aged younger than 21 years. The rate of SARS-CoV-2 infection in the same age group is 322 per 100,000, Levin said.

“Most patients with MIS-C have antibodies against SARS-CoV-2, and virus is detected in a smaller proportion,” Levin continued. “A relatively high proportion of cases have occurred among black, Hispanic, or South Asian persons.”

Hundreds of cases
According to researchers, as of May 10, 191 potential cases had been reported to the New York State Department of Health. Of the 95 confirmed and four suspected cases, 54% of patients were male, 40% were Black and 36% were Hispanic. Two patients died.

Most patients were younger than age 13 years. According to the authors, 31% were aged between 0 and 5 years and 42% were aged between 6 and 12 years. All patients presented with a fever or chills, 97% of had tachycardia, 80% had gastrointestinal symptoms, 60% had a rash, 56% had conjunctival injection and 27% had mucosal changes.

Elevated levels of C-reactive protein were found in all patients, whereas elevated levels of D-dimer were found in 91% of patients, and elevated levels of troponin were found in 71%, the researchers reported. Most patients — 62% — received Vasopressor support, more than half (53%) had evidence of myocarditis and 80% received ICU care. The median hospital stay was reported to be 6 days.

The second study included 186 cases from 26 states. Among them, 62% were male and 70% tested positive for SARS-CoV-2. According to the researchers, 73% of patients were healthy previously. Eighty-eight percent of them were hospitalized after April 16.

Gastrointestinal (92%), cardiovascular (76%), hematologic (74%), mucocutaneous (74%) and respiratory (70%) organ involvement was common.

Eighty percent of patients required ICU care, 20% received mechanical ventilation and 48% received vasoactive support, according to the report. Four patients died. Elevations in at least four biomarkers indicating inflammation were found in 92% of patients.

‘Tip of the iceberg’
According to Levin, both the CDC and WHO definitions of the disorder “require evidence of SARS-CoV-2 infection or exposure — a requirement that is problematic, since asymptomatic infections are common and antibody testing is neither universally available nor reliable.”

“Direct comparison of the clinical and laboratory features of MIS-C with those of Kawasaki’s disease suggests that the new disorder is distinct from the latter,” Levin wrote — a distinction that experts had previously made to Infectious Diseases in Children.

“There is concern,” Levin wrote, “that children meeting current diagnostic criteria for MIS-C are the ‘tip of the iceberg,’ and a bigger problem may be lurking below the waterline.”

He noted that children in the United Kingdom meeting a broader definition of the illness “have included critically ill patients, patients meeting diagnostic criteria for Kawasaki’s disease, and some patients with unexplained fever and inflammation.”

“Clinicians face difficult management issues as they see such a wide spectrum of patients,” Levin wrote. “What treatments may prevent progression to shock and multiorgan failure, and will treatment prevent coronary-artery aneurysms? Are children with self-resolving inflammation at risk for aneurysms, and what cardiac follow-up is needed? Such questions require studies involving not only the patients whose condition meets the current definitions but also children and adolescents who have unexplained fever and inflammation.

“Indeed, the case definitions may need refinement to capture the wider spectrum of illness,” he concluded. “The challenges of this new condition will now be to understand its pathophysiological mechanisms, to develop diagnostics, and to define the best treatment. Most patients to date have been treated with agents that have shown benefit in Kawasaki’s disease or other inflammatory disorders; thus, trials are needed to establish the appropriate therapy.”

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