New Information on Multisystem Condition Related to Pediatric COVID-19

Parents have a lot of worries – many of them justified -- about multisystem inflammatory syndrome in children, a rare manifestation of COVID-19. A new review from the CDC and Emory University School of Medicine provides information that pharmacists can pass on to those expressing concerns. Here is more information.

ATLANTA – Most children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild cases that do not lead to medical intervention. For a few pediatric patients, however, multisystem inflammatory syndrome in children (MIS-C) can cause severe symptoms.

An article published in the New England Journal of Medicine adds to the understanding of the epidemiology and clinical course of MIS-C. Key information provided by the COVID-19 Response team at the national Centers for Disease Control and Prevention and Emory University School of Medicine include MIS-C’s temporal association with COVID-19.

To reach their conclusions, the study team conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. Included in the case definition were six criteria:

  • serious illness leading to hospitalization,
  • an age of less than 21 years,
  • fever that lasted for at least 24 hours,
  • laboratory evidence of inflammation,
  • multisystem organ involvement, and
  • evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with COVID-19 in the past month.

Results came from 186 patients with MIS-C in 26 states. Researchers report that the patients’ median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020.

The study found that organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%).

Median duration of hospitalization was seven days (interquartile range, 4 to 10), 148 patients (80%) receiving intensive care, 37 (20%) getting mechanical ventilation, 90 (48%) being put on vasoactive support, and 4 (2%) dying. The article also recounts how coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki’s disease–like features were documented in 74 (40%).

Researchers point out that most of the patients -- 92% -- had elevations in at least four biomarkers, indicating inflammation. In terms of treatment, the use of immunomodulating therapies was common, with intravenous immune globulin administered to 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%).

“Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents,” the authors conclude.

Background information in the report advises that clinicians in the United Kingdom reported a cluster of eight previously healthy children presenting with cardiovascular shock, fever, and hyperinflammation in late April 2020.

By May 14, 2020, the U.S. CDC had issued a national health advisory to report on cases meeting the criteria for MIS-C. A published case series found that many of the pediatric patients with this hyperinflammatory syndrome have had fever and mucocutaneous manifestations similar to those of Kawasaki’s disease, a rare vasculitis of childhood that can cause coronary-artery aneurysms.

Some patients have presented with features of toxic shock syndrome, secondary hemophagocytic lymphohistiocytosis, or macrophage activation syndrome, according to the report.

“Although the cause of Kawasaki’s disease remains unknown, a preceding or active infection has been suspected,” the authors point out. “Like Kawasaki’s disease, MIS-C is a syndrome with a range of clinical presentations and an absence of pathognomonic findings or diagnostic tests. Unlike Kawasaki’s disease, however, MIS-C has been suggested in early reports to predominantly affect adolescents and children older than 5 years of age and to be associated with more frequent cardiovascular involvement.”

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