New findings in COVID-related kids' syndrome, Kawasaki disease

Doctor and nurse checking on girl in hospital bed
Doctor and nurse checking on girl in hospital bed

Kiwis / iStock

Two studies today describe new findings in the COVID-19–associated multisystem inflammatory syndrome in children (MIS-C) and the distinct but similar Kawasaki disease (KD).

Low blood pressure, shock, heart dysfunction

In the first study, published in JAMA Pediatrics, a team led by researchers from the US Centers for Disease Control and Prevention (CDC) used lab data to compare geographic and temporal distribution of MIS-C from March 2020 to January 2021 with that of COVID-19 over the same period.

In the largest known cohort of MIS-C patients and their distributions across the United States, the cumulative incidence was 2.1 per 100,000 people 21 and younger and varied by state, from 0.2 to 6.3 per 100,000. The death rate was 1.4%.

Of the 1,733 MIS-C patients, 90.4% had involvement of at least four organ systems, 54% had low blood pressure or shock, 58.2% required intensive care, and 31.0% had abnormal heart function. Pericardial effusion (fluid buildup in the sac around the heart) occurred in 23.4%, myocarditis (inflammation of the heart muscle) in 17.3%, and coronary artery dilatation or aneurysm (ballooning of a vessel wall) in 16.5%.

Patients 18 to 20 years had the most severe MIS-C signs and symptoms, with 30.9% having myocarditis, 36.4% having pneumonia, and 18.2% having acute respiratory distress syndrome (ARDS). This age-group was also most likely to report having a previous coronavirus-like illness (63%). In contrast, children 0 to 4 years old had the fewest severe MIS-C signs and symptoms, but 38.4% had low blood pressure or shock, and 44.3% required intensive care.

Gastrointestinal symptoms, rash, and conjunctival hyperemia (an inflammatory eye condition) occurred in 53% to 67% of MIS-C patients. Other common symptoms included fever, vomiting, rash, and diarrhea. Among all MIS-C patients, 57.6% were boys, 71.3% were Hispanic or Black, and the median age was 9 years.

Delayed immune response to coronavirus

States with the heaviest burden of MIS-C were generally in the West and Midwest. The first two nationwide peaks of MIS-C occurred 2 to 5 weeks after COVID-19 spikes and viral spread from urban to rural areas.

Most cases of MIS-C are thought to occur after asymptomatic or mild COVID-19 infections, with an outsized inflammatory response coinciding with peak antibody production several weeks later, the authors said.

"The geographic and temporal association of MIS-C with the COVID-19 pandemic suggested that MIS-C resulted from delayed immunologic responses to SARS-CoV-2 infection," they wrote. "The clinical manifestations varied by age and by presence or absence of preceding COVID-19."

The researchers called for development of lab markers or diagnostic tests to distinguish MIS-C from severe COVID-19 and other inflammatory conditions such as Kawasaki disease. "Physicians should maintain a high index of suspicion for MIS-C to promptly diagnose and treat these patients," they concluded.

In a commentary in the same journal, Jennifer Blumenthal, MD, and Jeffrey Burns, MD, MPH, both of Boston Children's Hospital, said that the study findings show that the lack of prior coronavirus symptoms, especially in younger children, shouldn't reassure pediatricians that MIS-C hasn't affected their hearts.

"If the entirety of the world’s pediatric population is at risk for COVID-19 and vaccination will be delayed in the pediatric population compared with adults, this potentially severe outcome must remain at the forefront of the differential diagnosis for pediatricians across the world pending further outcome research," they wrote.

Kawasaki disease spread likely airborne

Published in JAMA Network Open, the second study was led by researchers at Fukuoka Children's Hospital in Japan to determine the role of droplet versus contact transmission of KD. The longitudinal study involved 1,649 patients with KD and 15,586 patients with infectious diseases hospitalized at six centers from 2015 to 2020.

KD is an acute illness that affects mostly children 6 months to 5 years old—median age in the KD cohort was 25 months—and features inflammation of small and medium blood vessels. Although the cause of KD is unknown, it is believed to occur in genetically predisposed children after exposure to an environmental trigger such as an infection.

The researchers found that the number of hospitalizations for KD didn't change significantly between April and May in 2015 to 2019 compared with the same months in 2020 (mean, 24.8 vs 18.0 admissions per month; 27.4% decline; adjusted incidence rate ratio [aIRR], 0.73).

Over the same time, however, hospitalizations for droplet- or contact-transmitted respiratory tract infections fell from a mean of 157.6 to 39.0 admissions per month, a 75.3% decline (aIRR, 0.25), as did those for gastrointestinal infections (43.8 to 6.0 monthly admissions), an 86.3% decrease (aIRR, 0.14), for 12,254 fewer infections.

As a result, the ratio of KD to droplet- or contact-transmitted respiratory tract and gastrointestinal infections increased significantly in April and May 2020 (ratio, 0.40 vs 0.12).

"These findings suggest that transmission by contact or droplets is not a major route for KD development in Japan and support the findings of previous epidemiological studies indicating that KD may be associated with airborne disease in most cases. More extensive studies are warranted for further understanding of this intriguing disease," the authors wrote.

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