Resurgence of Kawasaki Disease After COVID-19 Pandemic

Source: Nakata F, Matsubara K, Hamahata K, et al. Resurgence of Kawasaki disease following relaxation of coronavirus disease 2019 pandemic restrictions in Japan. J Pediatr. 2024:275:114251; doi: 10.1016/j.jpeds.2024.114251.Investigators from multiple institutions in Japan conducted an ecologic study to evaluate the association of non-pharmaceutical interventions (NPI) during the COVID-19 pandemic and the incidence of Kawasaki Disease (KD). For the study, surveillance data on KD cases in Kobe City, Japan, between 2019 and 2023 were reviewed. Information on cases of KD included age, whether the KD presentation was complete or incomplete, resistance to intravenous immunoglobulin (IVIG) treatment, and coronary artery abnormalities. The incidence of KD in 3 periods was assessed: pre-pandemic (2016–2019), while stringent NPI were in place (2021–2022), and when NPI were relaxed (2023). The overall incidence rate during each of these periods, and in children in different age groups, was calculated. Data from multiple surveillance systems were used to evaluate trends in COVID-19 and multiple other infections in children between 2021 and 2023. The age of patients with KD during the pre-pandemic period (2016–2019), infection control period (2021–2022) and relaxed period (2023) were compared with Mann Whitney U tests. Differences in proportion of KD cases that were incomplete, associated with resistance to IVIG treatment, and complicated by coronary artery abnormalities were assessed with chi-square and Fisher exact tests.Data were analyzed on 907 children with KD in 2016–2019, 323 in 2021–2022, and 243 in 2023. The median age of KD patients during the 2021–2022 period was 22 months, compared to 30 months during 2023 (P <0.001) and 28 months in 2016–2019 (P = 0.009). There were no significant differences in proportion of incomplete cases of KD or KD complicated by IVIG treatment resistance or coronary artery abnormities between 2021–2022 and 2023. The percentages of children with KD who had a history of recent COVID-19 also were similar during the 2 periods (2.5% in 2021– 2022, 3.0% in 2023; P = 0.77). Overall, the incidence of KD per 100,000 children aged 0–4 years was 327.5 in 2016–2019, 281.3 in 2021–2022, and 426.7 in 2023. Compared to 2016–2019, in 2021– 2022, rates of KD were similar in children <2 years old, but lower in older children. Conversely, rates in all-aged children were higher in 2023 compared to 2016–2019. There was no apparent association between rates of COVID-19 in children and rates of KD. Similarly, there did not seem to be an association between rates of other individual infectious diseases and KD between 2021 and 2023, but the increase in KD in 2023 coincided with a collective increase in respiratory infections.The authors conclude that rates of KD fell during the period when stringent NPI were in place because of COVID-19 and resurged when NPI were relaxed in 2023.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.KD, an acute, febrile systemic vasculitis, has an annual incidence of 20 per 100,000 US children <5 years of age and is the leading cause of acquired heart disease in children in developed countries.1,2 Despite more than 50 years of research, the cause of KD remains unknown.3 Epidemiologic and clinical features suggest an environmental or infectious trigger in genetically susceptible individuals.4 The current researchers from Japan, the country with the highest incidence of KD,3 reported that cases of KD decreased with NPI during the COVID-19 pandemic and then resurged in 2023. This pattern also was noted in the US, with a 28% reduction in KD cases across 30 clinical centers in 2020– 20225 and a resurgence to usual numbers in 2023.3 In the US and Japan, common respiratory viral infections essentially disappeared during the pandemic, but KD did not.3,6 From 2020–2022, the numbers of patients <1 year of age with KD did not significantly change in San Diego County, CA, where there is active surveillance for KD cases.3 This raises concern that there is a prevalent exposure occurring in the home that contributes to infant cases.5 The peak age of KD occurrence in the US is 6 to 24 months.4 If there is an infectious trigger, the age predilection for KD may be explained by passive maternal antibodies protecting those <6 months and acquired immune responses protecting older children.3During the COVID-19 pandemic, a new entity, multisystem inflammatory syndrome in children (MIS-C), emerged.7 MIS-C shares several clinical features with KD. As we study the pathobiology of MIS-C, our understanding of the role of infection as a potential trigger for KD may be enhanced.Rates of KD declined when NPI were implemented during the COVID-19 pandemic and resurged in 2023 with the return of respiratory infections, supporting the hypothesized infection-triggered pathogenesis of KD. (See AAP Grand Rounds. 2024;51[1]:5.)8