COVID-19 and Kawasaki disease in children.

Coronavirus disease 2019 (COVID-19), caused by infection with a new type of coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first emerges in December 2019 and soon become a global health emergency. As of May 5, 2020, more than 3.6 million people worldwide have been diagnosed with COVID-19. However, little is known as to SARS-CoV-2 infection in children except that clinical presentations of COVID-19 symptoms in children are generally milder than those in adult patients [1]. Further information is urgently warranted to delineate the clinical features and disparate epidemiology of COVID-19 in children which is important for clinical and containment strategies.

Over the last few weeks, there has been apparent cluster of children presenting with Kawasaki disease (KD)-like symptoms in United Kingdom, United States and Italy (https://time.com/5832461/kawasaki-disease-covid-19/). The reported cases have overlapping blood parameters and presenting symptoms consistent with COVID-19 in children. Some of these children patients have confirmed SARS-CoV-2 infections by RT-PCR. Even though the relationship of KD to COVID-19 is not yet defined, there is growing concern of SARS-CoV-2 infection related inflammatory syndrome as a possible link between coronavirus infection and KD affecting young children. Congruent with this notion, one recent study has described a case of a 6-month-old baby diagnosed with classic KD, who was also tested positive for COVID-19. The patient received recommended treatment with intravenous immunoglobulin (IVIG) and aspirin, which leads to alleviation of clinical symptoms [2]. High incidence of a severe form of KD was also observed in another COVID-19 cohort from Bergamo province of Italy [3]. Both studies reinforced the potential link between COVID-19 and KD, and advanced our understanding of both diseases in children.

KD is a seasonal and rare but potentially severe inflammatory condition in children, mostly occurring in those under the age of five. It is a form of vasculitis-inflammation in blood vessel walls [4]. It was first reported by Japanese pediatrician Dr. Tomisaku Kawasaki in the 1960s. To date, the cause of KD, is unclear, but as-yet-unidentified infectious pathogens (termed as pathogen "X") may be the root-cause. One pronounced feature of KD is high and persistent fever, which responds poorly to anti-fever medications. Most children recover completely from KD after a few weeks, but early treatment is necessary to prevent possible complications. One severe form of complications is coronary artery aneurysms, the rupture of which leads to thrombosis formation and myocardial infarction [4]. In light of the recent observation of increased accumulation of inflammatory cells with the endothelium, heightened endothelial inflammation and injury/dysfunction occurs after SARS-CoV-2 infection probably via endothelial ACE2. The systemic inflammatory response to pneumonia may potentiate the inflammatory response within coronary lesions, rendering endothelial dysfunction [5] and therefore accelerating KD development. Therefore, SARS-CoV-2 infection and hyperinflammation in COVID-19 could be acting as the "priming trigger" that could lead to KD (Fig. 1 ). However, the definitive link between the childhood KD and COVID-19, needs to be confirmed in large cohort of infant and children patients worldwide.

Fig. 1

The possible link between COVID-19 and Kawasaki Disease (KD).

COVID-19 cases of children in the UK, US and Italy show KD-like symptoms which sparks concern about a possible link to COVID-19, as both disease show similar signs of fever. KD causes vascular inflammation and restricts blood flow to the heart. The rare inflammatory condition present in KD may be a possible complication of coronavirus infection in young children. The emergence of KD patients with SARS-CoV-2 positive testing indicates the unrecognized importance for KD patients to be tested for COVID-19. This is an important aspect as many parents hesitate to go to hospital due to the “stay-at-home” executive orders and fear of in-hospital infection [6]. As a result, KD may be underdiagnosed or not treated in a timely manner. However, without timely treatment, coronary artery aneurysms (CAA) could occur in up to 25 % of children with KD [6]. Therefore, KD patients should be closely monitored for potential COVID-19 infection and quarantined after IVIG infusion and patient discharge if tested positive for SARS-CoV-2 infection. It is important to administer IVIG within 7 days since disease onset till KD symptoms gone and COVID-19 test negative. Therefore, the interconnection between COVID-19 and KD is important for pediatric care for sick children. It is intriguing that no reported KD or KD-like symptoms observed in pediatric patients in China since the outbreak of COVID-19 in China, raising the possibility of racial background and genetic susceptibility may play a role. Therefore, further confirmatory studies of the clinical characteristics of COVID- 19 in children from a global perspective and the potential mechanistic link between COVID-19 and KD are warranted.

Declaration of Competing Interest

None.