Kawasaki disease (KD) is an acute childhood illness, which has emerged as the most common cause of acquired heart disease in children in the developed world. Although the etiology of KD is not known, large body of evidences suggests that an infectious pathogen likely triggers the onset of disease.1
Amid coronavirus disease 2019 pandemic, many countries have implemented nonpharmaceutical interventions (NPIs). Following the implementation of NPI in South Korea since April 2020, a profound decrease in diagnosis of infectious diseases has been reported.
Herein, we conducted a cohort study to estimate the impact of NPI on incidence of KD in Korean children, using the nationally representative data.
Claims data from the Health Insurance Review and Assessment Service, a single-payer database capturing >95% of Korean population, was used to describe the patients 0–4 years old who had an inpatient encounter with a primary KD diagnosis from January 2012 to August 2020. The International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code M30.3 was used. This study was reviewed by the Korea University Anam Hospital and was deemed exempt from institutional review board oversight (IRB No. K2021-0817-001).
For each year, we related the number of cases to the respective age group to estimate the incidence per 100,000 patient-years for the corresponding months of 2012–2019 versus 2020. We defined the pre-NPI period as January to March and defined the post-NPI period as April to August of each respective year. To define the effect of NPI, we performed a difference-in-differences analysis.
The hospitalization rates per 100,000 patients for each time period and the difference-in-differences analysis for 2012–2019 versus 2020 are displayed in Figure 1 and Table 1. The hospitalization rates between the 2 periods were similar until April, when the KD-related hospitalization rate has declined significantly from –38.8% (April) to 81.7% (June) (Fig. 1). The difference-in-differences for 2012–2019 versus 2020 was –33.6 (–30.1 to –37.5).
TABLE 1. -
Difference-in-Differences for 2012–2019 vs. 2020 Between Pre- and Post-nonpharmaceutical Interventional Periods, South Korea
|Incidence (per 100,000)
||–33.6 (–30.1 to –37.5)
Post-NPI period indicates April–August of corresponding years; Pre-NPI period, January–March of corresponding years.
In this cohort study, we found a significant decline in diagnosis of KD in South Korea, following implementation of NPI in 2020. Our finding is in line with reports from elsewhere, which showed that the mitigation policies were associated with reduction in diagnosis of KD, supporting the theory that KD is caused by an infectious agent. Following the introduction of mitigation policies in the United States, there was a 40%–70% decline in diagnoses of KD compared with the previous years.2,3 In Japan, there was no significant change in the number of KD-related admissions; however, there was a significant decrease in admissions linked to contact- or droplet-transmitted infections suggesting that the persistence of KD decrease may be linked to airborne transmission.4
Previous studies showing remarkable reduction in transmission of infectious diseases in different pathogens in Korea. During the 2019–2020 influenza season, there was a profound decline in the percentage of patients with influenza-like illness compared with the previous 4 influenza seasons in Korea.5 During the same period, there was 44% decline of mumps incidence, 44% decline for varicella, 28% decline for pertussis, 22% decline for invasive pneumococcal disease, 14% decline in incidence of hepatitis A, but no change for hepatitis B incidences, compared with 2015–2019.6 Taken together, our findings best support the hypothesis that KD is caused by a common infectious agent that has decreased throughout 2020 following the NPI measures and may have led to KD in children with predisposition.
This study has some limitations. First, the decline of KD incidences may be related to a reduction of diagnostic rates due to a decrease in health-seeking behavior. As people may not choose to visit healthcare service amid coronavirus disease 2019 pandemic, a reporting bias may have occurred, however, deemed less likely given no changes in diagnosis of nonrespiratory or nonairborne infections (ie, hepatitis B). Second, inherent to the limitation of claims data, there may have been unidentified confounders that were not controlled. We therefore included hospitalized cases to ascertain the cases admitted and were diagnosed as KD and excluded nonhospitalized cases. Third, there are overlapping clinical features between KD and the condition termed multisystem inflammatory syndrome in children and, therefore, maybe subject to misclassification bias. However, the incidence of multisystem inflammatory syndrome in children in Korea has been low so far with only 3 cases reported to date, therefore, minimizing such risk.7 Despite these limitations, our finding shows additional information extrapolated from NPI measures in reducing disease burden from diseases that may be indirectly affected.
The decrease in diagnosis of KD in Korean children during the NPI implementation policy adds clue for etiology of KD and the establishment of preventive measures.
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