Although the pandemic of SARS-CoV-2 (COVID-19) has been relatively benign in children compared to adults, there is growing concern about an emerging syndrome that causes severe, sometimes fatal, outcomes in pediatric patients.
The Centers for Disease Control and Prevention (CDC) has named this condition multisystem inflammatory syndrome in children (MIS-C).
“On April 26, 2020, clinicians in the United Kingdom recognized increased reports of previously healthy children presenting with a severe inflammatory syndrome with Kawasaki disease-like features,” the CDC reported.1 “The cases occurred in children testing positive for current or recent infection by SARS-CoV-2 … based on reverse-transcriptase polymerase chain reaction (RT-PCR) or serologic assay, or who had an epidemiologic link to a COVID-19 case.”
Patients presented with a persistent fever and a variety of symptoms, including hypotension, multiorgan involvement, and elevated inflammatory markers. Of the eight cases in the United Kingdom, 75% of the patients were of Afro-Caribbean descent and one patient died.
“In early May 2020, the New York City Department of Health and Mental Hygiene received reports of children with multisystem inflammatory syndrome,” the CDC reported. “As of May 12, 2020, the New York State Department of Health identified 102 patients with similar presentations, many of whom tested positive for SARS-CoV-2 infection by RT-PCR or serologic assay. New York State and New York City continue to receive additional reports of suspected cases.”
The CDC did not report in deaths among the U.S. cases and said it is unclear whether the syndrome also could strike adults. The CDC issued a case definition and urged reporting of any cases. The CDC case definition for MIS-C is summarized as:
- an individual aged < 21 years presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (> 2) 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 four weeks prior to the onset of symptoms.
The CDC recommends that “healthcare providers report any patient who meets the case definition to local, state, and territorial health departments to enhance knowledge of risk factors, pathogenesis, clinical course, and treatment of this syndrome.”
‘Most Likely an Immune Response’
Some insight comes from Samuel Dominguez, MD, PhD, an infectious disease physician at Colorado Children’s Hospital in Aurora, who has been treating children with the syndrome.
“Based on the epidemiology, these kids are appearing after about four weeks of the peak of COVID-19 cases overall in the areas where they are seeing this,” he says. “What we are seeing most likely is an immune reaction or some sort of post-infectious inflammatory response to the virus. The vast majority are presenting with a pretty severe gastrointestinal complaints, severe abdominal pain, some with vomiting and diarrhea.”
Some of children are in shock when they are brought in and must be admitted to an ICU for blood pressure support, Dominguez says.
“All of these kids have multiple days of high fever and evidence of pretty higher inflammation in the body,” Dominguez says. “Some of them are presenting very similar to Kawasaki disease, meaning conjunctivitis, rhinitis, and rash.”
All of the children with the syndrome at Children’s Hospital have survived, but there have been deaths caused by MIS-C reported in the United States and Europe, he says. The CDC’s call for case reports should provide some much-needed data on the syndrome. “We don’t actually know how rare this is,” Dominguez says. “We don’t know the baseline of how many kids have been infected and how many people are in this population. So, there are multiple levels of trying to determine the incidence and prevalence. We think so far that is relatively rare, but I think we need more data to understand the exact rate.”
MIS-C is linked to coronavirus in the case definition by the CDC, but it is not thought that the syndrome itself is transmissible because it probably is an inflammatory immune response. “We are basing our infection control on whether they have a positive PCR test or evidence of active viral shedding at the time they are admitted to the hospital,” he says. “There is no evidence that someone who has MIS-C in the hospital can transfer that to another [patient] or their family, but they can definitely transmit SARS infection. And some patients who have SARS infection can go on to develop this more serious presentation due to their reaction to the virus. Who those kids are, we don’t really know. At this this point in time we don’t know what the risk factors are.”
The implications for children returning to school are weighty because some parents may see even a rare risk as too dangerous to expose to kids.
“That’s the million-dollar question,” Dominguez says. “I think the school decisions are best left to our public health authorities. I still think that this is a relatively rare event. The vast majority of kids who are getting infected with SARS-CoV-2 are doing very well compared to their adult counterparts.”
- Centers for Disease Control and Prevention. Multisystem Inflammatory Syndrome in Children (MIS-C) associated with coronavirus disease 2019 (COVID-19). May 14, 2020. https://emergency.cdc.gov/han/2020/han00432.asp