COVID-19 Pandemic Provides Glimpse Into Potential Cause of Kawasaki Disease in Children

During the COVID-19 pandemic, the incidence of children developing Kawasaki disease (KD) was significantly higher than that for other infectious diseases, suggesting that KD arises as a result of airborne infections, investigators concluded in a recent study.

The study, published in JAMA Network Open, provides evidence contradicting the dominant theory for KD development—that KD is associated with contact or droplet transmission of pathogens similar to how respiratory syncytial virus (RSV) causes respiratory tract infections and rotavirus causes gastrointestinal infections.

KD is an acute, self-limited, febrile disease predominately detected in children aged 6 months to 5 years. According to the American Heart Association, the disease is characterized by inflammation of the blood vessels, particularly the coronary artery, potentially causing permanent arterial damage, aneurisms, and heart attacks.

Past evidence has suggested that KD can occur in patients who are genetically predisposed to the disease after being exposed to certain environmental triggers. However, despite long-term research, investigators are still unsure of what exactly causes KD development.

Since February 2020, when the first outbreak of COVID-19 occurred, Japanese officials heavily encouraged handwashing, mask wearing, and social distancing and issued a state of emergency lasting from April 7 to May 25, 2020. These measures decreased the spread of SARS-CoV-2, the virus that causes COVID-19, and other pathogens transmitted through contact or droplets, giving an opportunity to investigate whether the incidence of KD did as well.

To conduct the multicenter, longitudinal, cross-sectional study, the investigators analyzed the number of admissions for KD and infectious diseases at 6 hospitals in Fukuoka, Japan and 11 nationwide hospitals between 2015 to 2020.

A total of 1649 pediatric patients with KD and 15,586 with infectious diseases were admitted. The median (interquartile range) age for patients with KD was 25 (13-43) months, and 54.6% (n = 901) were boys.

There was no significant change in the number of KD-related admissions between April and May in 2015 to 2019 compared with the same months in 2020 (mean [SD], 24.8 [5.6] vs 18.0 [4.0] monthly admissions; 27.4% decrease; adjusted incidence rate ratio [aIRR], 0.73; 95% CI, 0.48-1.10; P = .12).

Conversely, there was a significant decrease in admissions linked to contact- or droplet-transmitted respiratory (mean [SD], 157.6 [14.4] vs 39.0 [15.0] admissions per month; 75.3% decrease; aIRR, 0.25; 95% CI, 0.17-0.35; P < .001) and gastrointestinal (mean [SD], 43.8 [12.9] vs 6.0 [2.0] admissions per month; 86.3% decrease; aIRR, 0.14; 95% CI, 0.04-0.43; P < .001) infections from April to May in 2015 through 2019 compared with the same time frame in 2020.

After the Japanese COVID-19 state of emergency was lifted in June to December 2020, the number of patients with KD significantly decreased by 45% in the 6 Fukuoka hospitals and 47% in the 11 nationwide hospitals compared with the same months in 2015 to 2019. However, the decrease was not comparable to the 68.9% decrease observed for respiratory infections. A smaller 18.2% decrease was observed for gastrointestinal infections.

“These persistently low RSV and rotavirus incidence rates suggest that people continued engaging in infection-preventive behaviors (eg, physical distancing, hand washing, and wearing masks) even after the COVID-19 state of emergency was lifted,” wrote the investigators.

The investigators suggested that the persistence of KD decrease may be linked to airborne transmission partially being blocked by COVID-19 preventive measures or potential KD-causing environmental triggers were reduced as a consequence of restricted socioeconomic activity, leading to reduced motor vehicle emissions and shutdowns of power plants and factories.

The limitations associated with the study included the limited potential for generalizability and the inability to definitively determine PD pathogenesis.

“Despite these limitations, we believe that the results of this work provide intriguing clues toward clarification of the pathogenesis of KD and the establishment of preventive methods for KD,” wrote the investigators.

Reference

Hara T, Fununo K, Tamanura K, et al. Assessment of pediatric admissions for Kawasaki disease or infectious disease during the COVID-19 state of emergency in Japan. Published online April 6, 2021. Accessed April 8, 2021.