Similar symptoms and outcomes among children treated in New York City and London were highlighted during a recent CDC Outreach webinar.
Most of the 37 children with pediatric multisystem inflammatory syndrome, temporally associated with COVID-19 (MIS) in London have experienced only mild versions of the syndrome, reported Michael Levin, MBE, PhD, professor of pediatrics and international child health at Imperial College in London, presenting data from a group of London colleges during CDC’s Clinician and Community Outreach webinar, “Multiinflammatory Syndrome in Children Associated with COVID-19
“Most children seemed to have very mild disease. Few ended up becoming critically ill”—the only “good news,” Levin said.
Similarly, in the 44 cases at Cohen Children’s Medical Center in New York City, there have been no mortalities from MIS, said James Schneider, MD, chief of Pediatric Critical Care Medicine and associate professor of pediatrics for Cohen.
The children are also responding well to treatment. Eighty-two percent of the initial 33 cases have been discharged. “There are a few still hospitalized but also seem to be responding,” Schneider said.
In both London and New York, most of these children were previously normal healthy children with no underlying comorbidities.
The majority of children tested negative for SARS-CoV-2 by polymerase chain reaction (PCR) in London but were positive for the antibodies to the virus. As a result, it is likely that MIS is mediated by the development of acquired immunity to COVID rather than by direct viral injury, Levin said.
In New York City, the vast majority also tested negative for acute SARS-CoV-2. “However, the vast majority if not, I believe, all of our patients were positive for the IgG immunoglobulin for SARS-CoV-2…indicating the previous infection,” Schneider said.
Throughout the UK, there was a higher incidence of MIS among children from black African, Caribbean, and British ethnicity—accounting for approximately 46% of the cases, Levin said. Similar racial disparities were reported in New York, where around 25% were black, around 27% were Hispanic, and around 10% were Asian or white. “That may potentially just reflect our particular demographic of where we are in New York. However, as we collect more and share more data throughout the country, we'll get a better sense of any kind of racial disposition,” Schneider said.
Presenting symptoms, rapid progression
In London, patients’ predominant presenting feature was shock with clear features of myocardial impairment. Unlike adults with COVID, only a third had predominantly respiratory problems.
The British children had a variety of symptoms, including sore throat, and headaches, “but particularly abdominal pain and vomiting,” Levin said. Some of them had rash, some of them had conjunctivitis or conjunctiva injection, raising concerns about a similarity to Kawasaki disease or Staphylococcal toxic shock syndrome, Levin said.
“And this problem progressed rapidly to shock and organ dysfunction,” he added. They had a marked elevation of C-reactive protein, marked elevation of neutrophils, profound lymphocytopenia, and elevated D-dimers, he added. Doctors also noticed that some had marked elevation of troponin and brain natriuretic peptides, suggesting a cardiac injury.
“The case definition which we used was a child presenting with persistent fever, inflammation with neutrophilia, elevated C-reactive protein and lymphopenia. Evidence of single or multiple organ dysfunction of which shock, cardiac, respiratory failure, renal, gastrointestinal or neurological disorders were possible,” Levin said.
At New York's Cohen Children’s Center, many of the children had multiple organ involvement and 21% had some degree of acute liver injury. Almost three-quarters had evidence of acute kidney injury, Schneider said.
“There was significant involvement of coronary enlargement and coronary aneurysms, which is quite early if compared to typical Kawasaki….and is also a significant higher burden of coronary involvement compared to typical Kawasaki. Again, illustrating perhaps a different disease process altogether,” Schneider said.
Most of the children had fever for at least 4 days along with gastrointestinal symptoms, rash, conjunctivitis, oral mucosal changes, respiratory symptoms of cough, and neurologic symptoms. “These children also had to have significant findings of inflammation, so elevations in the C-reactive protein, ferritins…also cardiac involvement with troponin or B-type natriuretic peptides,” Schneider said.
A striking feature in the UK was the prominence of abdominal symptoms, with a number of the children having abdominal pain, vomiting, and diarrhea. Renal injury was common with raised creatinine, but only one child required renal replacement therapy.
Five out of the first 19 London patients had evidence of coronary artery dilatation. And one child had a giant coronary artery aneurysm, Levin said.
Rash occurred in just over half of the children. Thirty percent have had conjunctival injection, and 20% had mucous membrane inflammation or red, cracked lips. “So a low proportion having features that were similar to Kawasaki disease,” Levin said.
Treatment and response
UK physicians gave the children a range of immunomodulator treatments, “largely because of the extreme evidence of inflammation in laboratory findings, and also because some of the patients had features suggestive of Kawasaki disease,” Levin said.
Intravenous immunoglobulin was the most common immunomodulator used, given to 62% of the patients. Some patients received immunoglobulin and steroids such as anakinra and infliximab. And some received azithromycin as part of COVID treatment.
In New York City, the children first received therapies for shock, including inotropes or vasopressors, and mechanical ventilation. Every chid received intravenous immunoglobulin. Most also received some type of corticosteroid, generally methylprednisolone, along with aspirin, Schneider said.
“The majority of patients responded quickly to treatment,” Levin said.
However, one child died as a complication of extracorporeal membrane oxygenation with an intercranial thrombus and then hemorrhage. In general, the patients had a slower response than in many other infections. “And a number of them took quite a considerable amount of time to come out of intensive care,” Levin said.
Future UK and US research
The CDC is working with local and state health departments to establish a national monitoring system to “better understand the burden and assess any potential risk factors for MIS and its temporal association with the COVID-19 pandemic,” said Ermias Belay, MD, special investigations team lead, COVID-19 Response with the CDC.
“And as the COVID-19 pandemic continues, and probably even through the fall, we urge clinicians to contribute to this national monitoring system by reporting cases to their local and state health departments,” Belay said.
Meanwhile, major studies on the illness have been launched in the UK and Europe.
The Diamonds study, led by a team at Imperial College, includes 11 countries in Europe. It “aims to understand the biology of the disease by undertaking RNA transcriptome analysis, proteomic analysis, and genetic analysis, not only of COVID or this emerging spectrum of disease, but all infectious and inflammatory diseases,” Levin said.
Another study, "the best available therapy study," or BATS is a multicountry study of the best treatment for pediatric MIS. “We're inviting pediatricians all over the world to enroll patients,” Levin said.