INTRODUCTION

Coronavirus is a virus which originated in Wuhan China, in late 2019. The coronavirus was then
spread around the world. Thus, becoming a pandemic. This name was given by the World Health
Organization (WHO) on 11th February 2020. SARS-CoV-2 is another name for Covid-19 which
means severe acute respiratory syndrome coronavirus .The scientists found that a part of the
SARS-CoV-2 spike proteins contains the RBD (receptor binding domain), and researchers noted
that the RBD had evolved to successfully locate and attached themselves to ACE2, which is a
receptor involved in the regulation of blood pressure. The Covid-19 spike protein can easily bind
to the human cells. Therefore, this proved that the Covid-19 is caused by natural selection and
was not manufactured in the laboratory. Kawasaki is a disease that causes blood vessels
inflammation and can lead to heart diseases. Latest report said that Kawasaki affects mostly
children and people who are in the 20s.

It is observed that the most the Asian countries for instance Japan has a higher prevalence of
Kawasaki disease with 239.6 per 100,000 children of incidence rate in 2010 compare to recently
which was 264 per 100,000 children. Kawasaki is believed to link to the environment of a child,
it can be cause by virus, bacteria, genes. Recently, since Covid-19 is causing much harm in the
world reports found that SARS-CoV-2 is believed to cause the Kawasaki syndrome, it is because
people infected by Covid-19 have symptoms of inflammatory disease same as the Kawasaki
patients. Also, people having Kawasaki symptoms are tested positive for Covid-19 antibodies so
Kawasaki syndrome can be linked to Covid-19.
 1.0 DESCRIPTION OF THE DISEASES
1.1 Kawasaki disease
Kawasaki disease (KD) is a disease whereby inflammation of blood vessels occurs
systematically, influencing mainly arteries which are medium in size. The disease was identified
in 1967 by Tomakisu Kawasaki, when he gave a comprehensive description of 50 children who
experienced a type of vasculitis. In developed countries, Kawasaki Disease is regarded as being
the most prevailing acquired cardiac state in childhood. Coronary arteries are usually the most
affected blood vessels. However, inflammatory changes can be observed in all the arterial
vessels of the body.

Major symptoms of Kawasaki Disease comprise:

◦ Conjunctivitis
◦ Fever
◦ Affection of mucous membrane and skin
◦ Cervical lymphadenopathy
Serious sequelae such as cardiac infarctions may occur if ever there are delayed treatments,
treatment refractory cases or omitted misdiagnosis. KD patients are generally under 5 years old,
with an average of 2 years old. Yet, there have been reported cases in younger patients. Patients
of 12 months or younger have higher chances of developing coronary arteryaneurysms. This is
especially concerning as patients of this age group may not be properly diagnosed sometimes,
because the disease presentation in these patients are usually ‘incomplete’.

Although the disease has been reported around the globe, in all ethnicities, KD occurs more
commonly in Japan, where roughly 240 in 100 000 children, under the age of 4 is affected. In the
USA, about 17 in 100 000 children are affected, and in the Caucasian populations, around 9 in
100 000 children are affected.

Up to now, the etiology of KD remains unknown. The possible presence of genetic components
is indicated by the occurrence of familial clusters alongside a rise of incidence in Asian
communities. In a variety of populations, genetic variants affiliations have been confirmed
(Table 1).
 Table 1. KD gene associations and their predicted effects.

(Source: Adapted from Hedrich et al. 2018)

In European KD patients, the transforming growth factor (TGF) pathway, contains genetic
variants connected with an increased risk factor to develop coronary aneurysms. All things
considered, it seems that variants in multiple genes related to immunological pathways might
influence genetic risk for KD to develop. The higher incidences in Asian populations might be
explained by a variation in genetic predisposition among distinctive populations. It has been
proposed that exogenous factors such as seasonal and regionals clusters, as well as reported
relations with wind directions, promote the expression of the disease in genetically susceptible
individuals. It has also been insinuated that infectious agents having low penetrance/transmission
rates may provoke subclinical disease in numerous individuals, and, equally cause KD in
genetically susceptible children. Another line of research implies that RNA virus infections are
present in some KD patients. A disease-associated pathogen that could be delivered by RNA are
present in bronchial epithelia of KD patients. Still, an explanation could not be delivered despite
exhaustive efforts in characterisation. Clinical criteria in Kawasaki disease have been
summarised, and are described in Figure 1 and Table 2.

Figure 1. Clinical criteria in Kawasaki disease (Source: Hedrich et al. 2018).

Table 2. Description of subfigures in Figure 1

Key points in epidemiology of KD are summarised in Figure 2.

Figure 2. Key points in Epidemiology of KD.

Key points useful in the diagnosis of KD in infants are described in Figure 3.

Figure 3. Key points that are crucial when KD is being considered as possible diagnosis in infants.

Treatments used for KD include the use of

 intravenous immunoglobulin (IVIG)

 acetylsalicylic acid.
1.2 Covid-19
SARS-CoV-2, a new member of the Coronaviridae family, is a positive-sense RNA virus which
possesses a non-segmented envelope. The virus forms part of the subfamily Orthocoronavirinae,
the genus beta (ꞵ), and the subgenus becovirus. Sars-Cov-2 is highly similar to viruses that have
previously caused epidemics around the globe, namely SARS-CoV (% identity=79%) and
MERS-CoV (% identity=50%). Additionally, the virus is highly similar to the bat coronavirus
RaTG13, procured from bats in Yunnan, China in 2013 (with a genetic similarity of 96.3%).
Evolutionary analysis and virus genome sequencing results provoked suspicions that bats may be
the natural host of SARS-CoV-2, that was then transmitted to humans by means of an unknown
intermediate. Nonetheless, the immediate origin of SARS-CoV-2 does not arise from bats. Latest
proofs demonstrated that SARS-CoV-2 propagated to humans through the mediation of
undomesticated animal commercialized in the Huanan Seafood Whole Market.

The virus affects mammals by targeting their respiratory system while affecting others organs.
SARS-CoV-2 employs the receptor angiotensin-converting enzyme 2 (ACE2), also used by
SARS-CoV, to infect humans. Potential fatal respiratory tract infections can be caused by the
virus. Symptoms which result from the infection of the lower respiratory tract by SARS-CoV-2
include:

◦ Fever

◦ Dry cough

◦ Dyspnea

◦ Headache

◦ Dizziness

◦ Generalized weakness

◦ Vomiting

◦ Diarrhea

The resulting disease from infection by SARS-CoV-2 virus is termed as ‘Covid-19’. The
symptoms of Covid-19 are largely diverse; they can range from negligible, similar to common
cold, to pronounced hypoxia accompanied by acute respiratory distress syndrome (ARDS).
 Figure 4. Structure of SARS-CoV-2 and mechanism used to infect human cells.

Figure 5. Possible mechanisms immune response generated after infection by SARS-CoV and
possibly SARS-CoV-2.
 Figure 6. Timeline of events since the discovery of Covid-19 until the month of February.

Figure 7. Updated illustration of COVID-19 epidemic up to February 2020.

As SARS-CoV-2 is a novel CoV, physicians lack experience to deal with Covid-19 patients.
Therefore, they mostly supply nurturing care to the patients, while simultaneously using a variety
of techniques which were previously utilized for the treatment of other forms of CoVs, like
MERS-CoV and SARS-CoV, or other viral infections. These include treatments with antiviral
drugs, plasma from recovered patients, steroids and immunosuppressants.
 2.0 LINK BETWEEN COVID-19 AND KAWASAKI SYNDROME
In countries with large outbreaks of coronavirus, some children who were tested positive for
Covid-19 have reported having symptoms of Kawasaki syndrome. Persistent fever (38-40°C) is a
symptom for both Covid-19 and Kawasaki syndrome.

It was noticed that the number of cases of kids infected with Kawasaki has never been reported
before the outbreak of Covid-19 (El-Bar, 2020). It was observed that among some children
infected with Covid-19, has symptoms of inflammations like Kawasaki disease (El-Bar, 2020).

Covid-19 infection tends to reduce the ability of T-cells to limit inflammation, and, since both
diseases cause heavy/excessive inflammatory responses, they may cause similar symptoms.

One should not hastily conclude that there is a link between Covid-19 and Kawasaki disease.

A recent study was carried out in Italy where Covid-19 has caused a lot of damage. The
conclusion was that SARS-CoV-2 epidemic was linked to the incidence of a more severe form of
Kawasaki disease.

One hypothesis is that since bacterial infection is opportunistic when there is a viral infection.
The immune system is already weak from fighting the virus and recovering, the bacteria may
invade and multiply more easily. Verdoni et al., (2020) reported that 8 out of ten children
suffering with the rare disease like Kawasaki had been tested positive for Covid-19 antibodies.
The potential reason for that might be because corona virus induces a massive immune response
leading to this shock.

There is one disease known to be similar to Kawasaki disease; it is called Multisystem

Inflammatory Syndrome in Children (MIS-C). It is a rare condition that can cause children to
become very ill for no apparent reasons. Its symptoms are similar to Kawasaki’s. With treatment
(like Intravenous immunoglobulin [IVIG]), it can easily be overcome.

However, even if the symptoms are Kawasaki-like, overall, the patient can be infected by Covid-
19.

It may also happen that MIS-C occurs in children with Covid-19 infection.

Many patients with MIS-C have been seen to have antibodies against the new coronavirus. This
suggests that MIS-C may be due to a delayed immune response to the virus.
In a study carried out by Verdoni et al., (2020), patient suffering from Kawasaki disease before
covid-19 is classified as group 1 and patient diagnosed with like Kawasaki disease after the
pandemic is classified as group 2.

Many differences were observed between the two groups:

1. The number of patients infected per months

2. The mean age of people affected
3. Cardiac involvement
4. Kawasaki disease shock syndrome (KDSS), in which Kawasaki disease is associated with
systolic arterial hypertension
5. Macrophage activation syndrome (MAS)
6. Adjunctive steroid treatment (AST)

Differences observed between the two groups based on distinctive factors, have been
summarised in Table 3.

Table 3. Comparison between the groups

Factors Group 1 Group 2

Patients per months 0.3 10
Mean age 3.0 7.5
Cardiac involvement two of 19  six of ten
KDSS zero of 19  five of ten
MAS zero of 19  five of ten
Need for AST three of 19 eight of ten
Source: (Verdoni et al., 2020)

In group 2, 50% of the patients was detected with incomplete symptoms of Kawasaki disease.
The group 2 patients shared similar clinical features with that of covid-19 patients. For e.g. they
had respiratory issues, gastrointestinal problems, cardiac involvement and meningeal signs.

These cases where children are affected with the rare disease is mostly found in regions where
Covid-19 has been at a higher rate such as Italy and New York City (DUCHARME, 2020).

According to these observations, it is thought to be a post inflammatory disease of the corona

virus. That is, the immune response to covid-19 is possibly responsible to the Kawasaki-like
disease.
Some scientists does not accept the fact that corona virus is linked to Kawasaki disease. They
explained that there is a clear difference between Kawasaki and Multisystem inflammatory
syndrome in children (MIS-C), which is the name given to the Kawasaki-like disease
(Ducharme, 2020). It was reported that the Kawasaki-like disease has more severe symptoms
compared to the typical Kawasaki (Ducharme, 2020). It is also observed that children with
covid-19 had heart muscle inflammation rather than coronary artery swelling which is observed
which Kawasaki disease (Samuelson, 2020).

In a study carried out by Eunjung (2020), she proposed that the Covid-19 might have a different
version of inflammatory response in children compared to adult where the inflammatory
response leads to respiratory problems.

The conclusion is that Covid-19 may be linked to an increase in the incidence of Kawasaki
syndrome. Covid causes the immune system to induce heavy inflammation in the body of
children and this may be the reason why Kawasaki symptoms are seen in kids.

However, MIS-C can be misdiagnosed as Kawasaki syndrome. In all cases, if any symptoms are
noticed in children, the parents should take them to the doctor immediately.

Further research is also needed, since Covid-19 is a new virus and may affect other systems.
Also, causes of Kawasaki syndrome are still quite unknown. This pandemic has shown that viral
infections can induce the disease.

3.0 CONCLUSION
At the present time Kawasaki disease is not only in Asia countries but is present all over the
world. Through many medical survey and studies it was shown that Kawasaki disease has a link
with covid-19 having some similar defense mechanism during immune response and many
patients suffered from Kawasaki disease tested positive for Covid-19. A higher prevalence of
Kawasaki disease was observed where children have been more exposed to Covid-19. Also, not
all researcher believed that covid-19 is associated with Kawasaki disease. Even if there has been
many clinical analysis and survey, the cause of Kawasaki disease remain uncertain. But, there
are many genetic studies which can be done in order to characterize the specific gene associated
in disease mechanism of Kawasaki. However without knowing the origin of this disease making
prevention more challenging. The prognosis and the complication of KD can be largely reduced
if there is early diagnosis of the disease and proper treatments are made. Further studies and
expert consensus with also several published experiences will help to properly manage and
understand the disease. Both clinicians and scientists are working together with the aim of
finding its etiology. Therefore, caution is necessary and a regular follow up is required for every
patient who have a history link with both Covid-19 and Kawasaki.