SARS-CoV-2–Related Mitigation Measures and Insights Into Kawasaki Disease

Abstract

Since Tomisaku Kawasaki first published the initial description of his eponymous disease 55 years ago, 1 investigators worldwide have endeavored to determine its pathogenesis. Although an infectious agent has long been suspected to trigger Kawasaki disease (KD), this has not been conclusively identified as the cause of the clinical syndrome characterized by fever, mucosal changes, rash, conjunctival injection, extremity changes, and unilateral lymphadenopathy. 2 While these classic criteria for KD are present only transiently, coronary aneurysms develop in up to 20% of children with KD in the first 6 weeks of disease. 3 This devastating complication, which can lead to angina, myocardial infarction, and sudden cardiac death, has driven the search for the pathogenesis of KD to develop both a pathognomonic test for early diagnosis and more targeted immunomodulatory treatments. However, the cause of KD has remained elusive despite decades of research. Now, in a natural experiment, societal changes to mitigate SARS-CoV-2 infection during the COVID-19 pandemic have exposed the importance of infectious and/or environmental exposures in the etiology of KD.In this issue of JAMA Pediatrics, Ae et al 4 present epidemiological evidence that etiologic agent(s) with a respiratory portal of entry have a seminal role in triggering KD. Since 1970, Japan has administered biennial nationwide surveys to hospitals specializing in pediatrics to study the epidemiology of KD, resulting in the world's largest KD data source. Using robust and carefully curated data from the 26th nationwide survey, the authors describe 3 important findings in comparing data from 2019 (17 347 patients with KD prepandemic) with data from 2020 (11 173 patients with KD during the pandemic). 4 First, KD cases decreased by 35.6% from 2019 to 2020, which was most evident during the special mitigation period in Japan (March through May 2020) when schools and day care facilities were closed. This reduction is highly notable given that the number of KD cases in Japan has steadily increased over the past 2 decades. 5 The highest rate recorded was 371 per 100 000 Japanese children aged 0 to 4 years in 2019. In 2020, the recorded rate in the same age group was only approximately 250 per 100 000, similar to the rate in 2006. The authors considered whether this striking reduction in incidence derived from reluctance of parents to bring their febrile children to medical care because of fear of contracting SARS-CoV-2 in medical settings. However, the number of days of illness at presentation did not differ between 2019 and 2020, with 96% of patients presenting by day 7 in both years, indicating that the lower incidence of KD was unlikely to have been caused by lower health care use or missed cases. Lastly, Ae et al 4 found that patient age affected the pandemic reduction of KD case numbers. Specifically, KD incidence fell more in children 2 years or older than in younger chil-