Kawasaki disease, also called as mucocutaneous lymph node syndrome, was first reported by a Japanese pediatrician, Dr. Tomisaku Kawasaki in 1967 . Kawasaki disease often occurs in young children, mostly under 5 years of age, with 1.5 times more in boys compared to girls . Consistent with this literature report, our study found that the median age of children with Kawasaki disease in the historical cohort was 15 months with the male-to-female ratio 1.54:1. We haven’t observed significant differences in age and sex between the patients with Kawasaki disease admitted to the isolation ward from January 1, 2020 to July 31, 2020 during COVID-19 pandemic and the historical cohort. An observational cohort study in Italy demonstrated the mean age of children with Kawasaki disease was 7.5 years , which is different from our findings. Epidemiological patterns vary widely from different regions, with incidence varying by race and season. The highest incidence has been reported in Japan with 239/1000000, followed by Korea with 113.1/100000 and Taiwan, China with 69/100000 . The incidence of Kawasaki disease hospitalizations has been reported in USA with 19/100,000 in children below 5 years of age . In Japan, Kawasaki disease is most prevalent in January (winter) and July (summer), as well as in Korea . In USA, the higher incidence in winter and spring has been discovered . Our data showed the higher incidence in summer (May, June and July) over the past five years. But the highest incidence in the current cohort was in March, two months after COVID-19 outbreak in Wuhan.
The pathogenesis of Kawasaki disease is not fully understood, which may be related to infection, immunity and genetic susceptibility . Nationwide epidemics of Kawasaki disease have occurred in Japan in the years 1979, 1982, and 1986 [23-25]. Seasonal variation have also been observed in many other countries, including but not limited to Europe. These findings suggested that infection may be a trigger for Kawasaki disease. So far, no specific pathogen has been confirmed to be absolutely associated with Kawasaki disease. Several case reports have linked Kawasaki disease with many pathogens such as Mycoplasma pneumoniae , cytomegalovirus , adenovirus, rhinovirus, enterovirus , bocavirus , parainfluenza type 3 and coronavirus OC43/HKU1 . Consistent with these reports, Kawasaki disease has been found to be associated with Mycoplasma pneumoniae, enterovirus, Epstein-Barr virus and adenovirus in our historical cohort and Mycoplasma pneumoniae and Epstein-Barr virus in our current cohort. In the past few months several case reports and a time-series analysis have demonstrated that Kawasaki disease is linked to a SARS-CoV-2 infection . SARS-CoV-2 nucleic acid test was performed in 13 cases and SARS-CoV-2 antibodies (IgM and IgG) was conducted in 11 cases in our current cohort, but no positive results were found. However, the incidence of Kawasaki disease during COVID-19 pandemic was significantly higher than that before COVID-19 pandemic, and Kawasaki disease associated with abnormalities of chest CT were also significantly increased. As shown in figure 1, ground-grass opacity (GGO) which is the initial chest CT feature of COVID-19 has not been found in our current cohort, but pleural thickening, fibrous strips, and subpleural nodules which are the follow-up chest CT changes of COVID-19 have been observed [32,33]. SARS-CoV-2 RT-PCR test results of pharyngeal swab specimens are variable and potentially unstable , the false-negative rate is as high as 66% on day 21 after infection . At present, there are insufficient studies to evaluate the duration of SARS-COV-2 antibodies . Considering that Kawasaki disease mainly occurred two months after COVID-19 outbreak in the current cohort, it is possible that these children with CT abnormalities have been previously infected with SARS-COV-2.
The relationship between COVID-19 and Kawasaki disease macrophage activation and Kawasaki disease shock has been reported in Italy and France [6-8]. In contrast, our data showed no increase in severe form of Kawasaki disease during COVID-19 pandemic in Wuhan. There were no significant differences in age, sex, clinical manifestations, blood routine examination, blood biochemistry, cardiac ultrasound and treatment between the historical cohort and the current cohort. The reason for this inconsistency may be related to race and genetic difference. We also compared our data with those of Europe, and we found the median age of children with Kawasaki disease in Wuhan were significantly younger than that reported in Europe [6-8]. We presumed that the immune response in younger children was not as strong as in older children, so there was no severe form of Kawasaki disease or multisystem inflammatory syndrome reported in Wuhan.
The present study has some limitations. This is not a multicenter retrospective analysis and may not perfectly represent the overall incidence of Kawasaki disease during COVID-19 pandemic in Wuhan. Further clinical studies with lager cohorts in China are required to confirm the findings of this study.
In conclusion, the present study retrospectively analyzed the characteristics of Kawasaki disease in isolation ward from January 1, 2020 to July 31, 2020 in a tertiary pediatric referral centre in Wuhan, China. This study found that Kawasaki disease mainly occurred in young children (87% were less than 2 years old) in Wuhan, and there were no MAS and KDSS during COVID-19 pandemic. All children with Kawasaki disease responded well to IVIG and aspirin. Although no definitive evidence of SARS-CoV-2 infection in these children with Kawasaki disease has been found, but the incidence of Kawasaki disease during COVID-19 pandemic was significantly higher than that before COVID-19 pandemic, and Kawasaki disease associated with abnormalities of chest CT were also significantly increased. This study suggested that there may be an association between the emergence of Kawasaki disease with non-severe form and COVID-19 pandemic in Wuhan.