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Multisystem inflammatory syndrome in children (MIS-C) has seen a surge in cases trailing the winter wave of COVID-19 in adults, but the treatment and recognition of it are better than in the earlier waves, clinicians and researchers say.

Over the last 30 days, there have been around 11 cases of this SARS-CoV-2 infection-linked syndrome at the Nemours Hospital for Children in Wilmington, Delaware, as compared with a high of six to eight per month in the spring wave and three or fewer a month over the summer and fall.

"We anticipated this," said Meg Frizzola, DO, chief of the pediatric ICU there. "After each holiday gathering -- Thanksgiving, Christmas, New Year's -- ... we saw a significant surge in COVID-19 cases. Now we're about 6 to 8 weeks out from those exposures, and that's the exact timeline of when MIS-C presents."

As the rates are declining in adults, MIS-C incidence should start to fall in a trailing lock-step, she added in an interview in which a public relations person was present.

But since the first wave, there have been improvements, she noted.

"We continue to refine our MIS-C pathway," she said. "Early on in the pandemic, we were using best evidence. Over time, both our inclusion criteria in terms of what should raise our red flags has certainly changed, as well as our laboratory studies and our imaging evaluations and our echo in addition to our treatment."

Illustrating the science that has trickled in, an analysis of more than 1,000 pediatric patients hospitalized from March 15 to October 31 across 31 states pointing to distinguishing characteristics for MIS-C compared with severe, acute COVID-19 infection:

• Younger age (40.8% ages 6 to 12 years vs 19.4%)

• Non-Hispanic Black (32.3% vs 21.5%)

• No underlying conditions (69.0% vs 37.9%)

MIS-C was more likely in children with more complex presentations: Cardiovascular and respiratory involvement nearly tripled the likelihood at 2.99-fold, while cardiovascular issues without respiratory involvement increased it nearly 2.5-fold, and mucocutaneous issues without cardiorespiratory involvement was associated with 2.29-fold elevated likelihood.

MIS-C was also linked to significantly higher neutrophil-to-lymphocyte ratio and lower platelets, Adrienne Randolph, MD, 0f Boston Children's Hospital, and colleagues reported in JAMA.

While MIS-C led to substantially more ICU admissions (73.8% vs 43.8% with severe COVID-19), the outcomes weren't too much worse with MIS-C than severe COVID-19: 10 of the 539 (1.9%) with MIS-C and eight of the 577 (1.4%) with severe COVID-19 died during hospitalization.

Cardiac involvement normalized for nearly all (91%) of the 34% of MIS-C cases with acutely reduced left ventricular systolic function by 30 days and for most of the 13% with coronary artery aneurysm (79%).

A in JAMA Otolaryngology–Head & Neck Surgery of 50 cases of what the British guidelines call pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) showed that at a median 60 days after acute presentation:

• 10% required ongoing voice therapy for dysphonia

• 8% had been treated for persistent loss of taste and smell that improved after intranasal corticosteroids

• 6% had ongoing swallowing therapy for dysphagia

• 6% had postinflammatory changes of the laryngeal mucosa

"Fortunately, as is the case for COVID-19 in pediatrics, the [adverse] outcomes and the mortality rate are remarkably low," Frizzola noted.

She said that in speaking with colleagues across the country, "what we are noticing is even the morbidities are going down, meaning the cardiac system recovers more quickly, the length of stay in the ICU is certainly shorter, the length of stay in the hospital is shorter."

Frizzola chalked it up to iteratively better treatment than the Kawasaki disease-type strategies initially thrown at MIS-C.

Now instead of starting with steroids and multiple doses of intravenous immunoglobulin (IVIG) for everyone, they're treated according to severity as indicated by a narrower range of lab and echo findings along with renal involvement. If patients don't respond sufficiently to a first dose of IVIG, "we then immediately go to anakinra [Kineret], which is an immune modulator," Frizzola noted.

Not everyone gets prophylactic aspirin for antithrombotic treatment anymore either. "We're not throwing the kitchen sink at them," she said.

Her hospital system is among the many with long-term surveillance of their MIS-C patients planned out to 6 months and 1 year. "I can't wait to have solid data 5 years from now," she said. However, the "nimble" multidisciplinary approach to gathering and constantly analyzing as much data as possible on these cases from the first recognition has made a difference, she argued.

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