Is Kawasaki Disease Triggered by Underlying Infection Like COVID-19 or Flu?

While Kawasaki disease prevalence is rare, it is possible that it may be triggered by underlying viral infections such as the novel coronavirus 2019 (COVID-19) or pandemic influenza, according to a paper published in The Lancet Child & Adolescent Health.

Investigators from Paris conducted a “quasi-experimental” retrospective review of patient data in order to examine Kawasaki disease through the lens of the COVID-19 crisis. While only 3% of reported COVID-19 cases are in patients younger than 20 years, investigators wrote, Kawasaki disease had spiked by April 2020, and was likely related to the COVID-19 outbreak.

There are no specific tests that can be used to confirm Kawasaki disease, but patients can be diagnosed with Kawasaki disease if they meet internationally accepted criteria. Patients who do not meet the criteria still may be diagnosed with incomplete Kawasaki disease.

The investigators collected data from 230 hospital-admitted Kawasaki disease patients in Paris, France, which they noted was a hotspot for COVID-19 in their country, from December 2005 to May 2020. The 134 boys and 96 girls were diagnosed with complete or incomplete Kawasaki and were aged between 1 month and 15 years.

As of April 2020, investigators observed a nearly 500% increase in Kawasaki disease hospital admittance, with 6 patients admitted per month.

“Thus, the increase of Kawasaki disease hospitalizations started 2 weeks after the first peak of the COVID-19 epidemic in the Paris region, which occurred around March 31 to April 1, 2020,” investigators wrote.

However, the increase in Kawasaki disease was unrelated to an increase in overall hospital admissions, because hospital admissions actually dropped since March 2020. Investigators attributed this to national stay-at-home orders during the COVID-19 outbreak. During this period, they also observed an “unprecedented” decreased in the proportion of other respiratory viruses among the Parisian population; again, likely due to the same orders.

Investigators presented data from 10 Kawasaki disease patients admitted between April 17 and May 16 of this year. Half had complete Kawasaki disease, while the other half had incomplete Kawasaki disease.

They found that 8 of 10 had a positive nasopharyngeal SARS-CoV-2 PCR test or positive SARS-CoV-2 serology. Another patient had prolonged exposure to another individual with confirmed COVID-19 but their PCR and serological tests for SARS-CoV-2 were negative.

The children also had other comorbidities, including 1 major coronary aneurysm and 5 with myocarditis. None of these patients required mechanical ventilation, though 6 patients required intensive care and 5 had inotrope treatment. Investigators reported no fatal outcomes.

The study authors also observed a peak of Kawasaki disease hospitalizations in December 2009, which they said coincided with the H1N1 influenza outbreak in November and December of that year in France. This peak occurred about 1-3 weeks after the peak of the flu outbreak, they said. But characteristics of Kawasaki disease patients admitted to the hospital related to the COVID-19 outbreak appeared different than those during the H1N1 outbreak.

“The only other peak in Kawasaki disease observed during the 15-year observation period occurred during the context of the H1N1 pandemic, suggesting that SARS-CoV-2 is not the only virus capable of triggering such an emergence of Kawasaki disease,” investigators wrote. “Seasonal patterns of Kawasaki disease have also been observed in many other countries, including in Europe and North America.”

The findings have led to the speculation that viral infections might underline Kawasaki disease pathogenesis. But large outbreaks seem to be a rare event, investigators concluded.