Multisystem inflammatory syndrome associated with COVID-19

One of the few comforting findings in the COVID-19 pandemic has been that most children older than one year of age have a less severe clinical course than adults. A large case series from China suggested that about half of infected children have mild symptoms (acute upper respiratory tract infection or gastrointestinal symptoms, including diarrhea) while only 1 in 20 develop hypoxia, respiratory failure, or other organ failure. In a U.S. case series, two-thirds of infants younger than 12 months were hospitalized; the corresponding figure in older children was 5 to 15 percent. As a pediatric infectious diseases specialist at New York University recently told a New York Times reporter, "The idea that children either don't get COVID-19 or have really mild disease is an oversimplification."

On April 7, Hospital Pediatrics published a case report of a 6 month-old infant who was hospitalized for classic Kawasaki disease and had a positive result on a reverse transcription polymerase chain reaction (RT-PCR) test for COVID-19. At that time, it was not clear if the COVID-19 diagnosis was coincidental or associated with this rare vascular inflammatory condition. On May 7, the Lancet published a report of a cluster of 8 cases of children with hyperinflammatory shock (atypical Kawasaki disease, Kawasaki disease shock syndrome, or toxic shock syndrome) who presented to a children's hospital in London during a 10-day period in the middle of April. Within one week, more than 20 children with similar clinical features were admitted to the pediatric intensive care unit (PICU), half of whom tested positive for SARS-CoV-2.

In Bergamo, Italy, the incidence of Kawasaki-like disease increased 30-fold between February and April at the height of the epidemic. Compared to a historical group of children with Kawasaki disease prior to the pandemic, these children were older and had a higher rate of cardiac complications. Investigators in France and Switzerland described a series of 35 children (31 of whom tested positive for SARS-CoV-2) who were treated in PICUs for acute heart failure due to a severe inflammatory state.

Last week, the U.S. Centers for Disease Control and Prevention (CDC) issued an official health advisory to provide information to clinicians about multisystem inflammatory system in children (MIS-C) associated with COVID-19. The case definition for MIS-C is as follows:

• 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 4 weeks prior to the onset of symptoms.

Fortunately, standard treatment for Kawasaki disease (described in a 2015 article in AFP), including intravenous immunoglobulin, corticosteroids, and aspirin, thus far appears to be effective in treating MIS-C associated with COVID-19.