Introduction

The Coronavirus disease 2019 (COVID 2019) caused by severe acute respiratory syndrome coronavirus 2 has rapidly spread worldwide. In March 2020, Morocco began seeing increasing numbers of COVID-19 cases, although children have been relatively spared [1, 2].

A secondary Multisystem Inflammatory Syndrome in Children have described after a prior COVID-19 infection who have presented with manifestations of vasculitis especially in young asymptomatic patients in England (n=8) and France (n=21) [3,4].

Kawasaki disease is the most common primary vasculitis in childhood, with medium and small sized arteries predominantly affected [5]. Although the cause of Kawasaki’s disease remains unknown, a preceding or active infection has been hypothesized, as several viral respiratory agents [6, 7]. One of the most severe complications of Kawasaki disease is coronary artery anevrysm [8]

The aim of this study was to describe the epidemiology, features and treatment of new cases of Kawasaki-like presentations during the SARS-CoV-2 epidemic.

Methods

A retrprospective, descriptive study was conducted in department of pediatrics at Mohammed V Military Teaching Hospital, Rabat including the notes of all children who were admitted with Kawasaki disease between 1 Nov 2020, and 31 Jan 2021.

Our department, located in the city of Rabat, capital of Morocco, is a tertiary pediatric referral centre with approximately 1000 pediatric admissions per year. This university service receives from all regions of the kingdom Cases were consists of all children admitted with Kawasaki like to the service during the study period. Kawasaki-like presentations were defined according to the criteria of the American Heart Association to define the presence of complete and incomplete Kawasaki disease [8]. For each patient we obtained nasopharyngeal swabs to test for SARS-CoV-2 using polymerase chain reaction (PCR; SARS-CoV-2). To exclude hospital acquired SARS-CoV-2 infection. We also took blood samples to test for IgG antibodies against SARS-CoV-2.

Factors analyzed were the demographic data, presenting symptoms and history of previous treatments, contact with confirmed or suspected cases of COVID-19, vital signs, and laboratory data, including such as for inflammatory and cardiac markers. Standard cardiology investigations included regular electrocardiography and echocardiography. A coronary artery dilation was defined if the coronary artery diameter z score was between 2.0 and <2.5 and an aneurysm if the z score was 2.5 or greater [8].

All patients were administered intravenous immunoglobulin at 2 g/kg. Patients were also treated with aspirin at 80 mg/kg per day for 5 days. Aspirin was maintained until 48 h after defervescence, and then continued at an antiplatelet dose of 3–5 mg/kg per day for 8 weeks.. Response to treatment was defined as the normalisation of vital signs, CRP, and blood tests, and the resolution of symptoms and signs.

Statistical analyses were performed using SPSS version. The Mann-Whitney U test was used for the comparison of the proportions. P < 0.05 was considered statistically significant.

Results

Characteristics of the sample

A total of 10 cases of Kawasaki like were included in the main analysis of this study. There was a higher proportion of males 7(70%), with a sex ratio of 2, 3. The median age at presentation was 8 (range 6-15). The 10 patients had no relevant personal or family medical history. All patients presented with a classic form of the disease. Among the principal criteria Two Patients had non-exudative conjunctivitis, hand and feet anomalies (33%), and polymorphous skin rash (90%). Five (50%) of ten patients had associated changes of the lips or oral cavity, or both; two patient also had laterocervical lymphadenopathy. Five patients had gastrointestinal symptoms, which occurred early in the course of Kawasaki disease and consisting of acute abdominal pain, often associated with vomiting and diarrhoe. One patient presented with headaches. In two (20%) patients, the echocardiography detected pericardial effusions. Myocarditis was diagnosed in 4 (40%) patients, with left ventricular ejection fraction ranging between 25% and 56%. Two patients had also a right coronary aneurysm (>6 mm)

Table 1: Clinical characteristics of children presenting with Kawasaki disease during the coronavirus 2019 pandemic.

Laboratory evaluation and imaging

All patients had significant elevated inflammatory markers including C reactive protein, erythrocyte sedimentation rate, elevated ferritin level, and procalcitonin. One (10%) patient had lymphopaenia, and a mild elevation in transaminases was noted in five patients. Hypertriglyceridaemia was shown in five (50%); fibrinogen was high in seven (70%) of ten patients, as was D-dimer (>500 μg/L)in eight (80%) of ten patients. Elevation of both cardiac troponin I (>26 pg/mL) and B-type natriuretic peptide BNP (>100 ng/L) were found in 7/10 (70%) and 6/10 (60%) patients, respectively Echocardiography detected Coronary-artery aneurysms in four (40%) patients on the basis of a z score of 2.5 or higher and increased coronary visibility in two (20%) patients.

Evidence of SARS -CoV-2 infection

No recent history of viral like symptoms was reported in all patients. History of recent contact with family members displaying viral-like symptoms was reported in 3 patients. The median interval between the reported contact and Kawasaki disease was 32 (range 25-60) days. RT-PCR testing for SARS-CoV-2 was positive in 1 case. IgG antibodies against SARSCoV-2 were detected in all patients (100%) patients. Multiplex PCR searching human seasonal coronaviruses, respiratory syncytial viruses, parainfluenza and influenza viruses, and in nasopharyngeal swabs, was negative in all patients

Table 2: Imaging and laboratory findings of children presenting with  Kawasaki disease during the coronavirus disease 2019 pandemic

Treatment

All patients received intravenous immunoglobulin (2 g/kg) and low dose aspirin (3-5 mg/kg/day). Four (40%) patients received inotropic agents for myocarditis with cardiac dysfunction. Median duration of vasoactive or inotropic agents was 6 (range 4-12) days.

Discussion

During this global pandemic with SARS-CoV-2, few paediatric observations labeled a formerly unknown complication of COVID-19, matching criteria of typical or atypical Kawasaki disease [9, 10, 11]. We describe 10 patients younger who match the criteria developed by the Centre of Disease Control the USA that was designed to be sensitive for multisystem inflammatory syndrome in children with serologic evidence of a previous COVID-19 infection [12].

Kawasaki Disease is an acute vasculitis of childhood and the leading cause of acquired heart disease in children in developed countries, with 50% of cases occurring in those <2 years of age, and 80% in those <5 years of age.4 The diagnosis of “classic” Kawasaki Disease is considered in patients presenting with fever for 5 days together with at least 4 out of 5 clinical criteria in the absence of an alternate diagnosis. Various studies have described an association between viral respiratory infections and Kawasaki disease ranging from 9% to as high as 42% of patients with Kawasaki Disease testing positive for a respiratory viral infection in the 30-days leading up to diagnosis of Kawasaki Disease [13,14]. Interestingly, Turnier et al. in 2015 described that 28% of positive results were attributable to rhinovirus/enterovirus, 8.7% due to parainfluenza, and the remaining pathogens: respiratory syncytial virus, influenza, adenovirus and human coronavirus (strains 229E, HKU1, NL63, OC43) were each positive less than 5% of the time [13].

The physiopathology of Kawasaki disease remains unclear. A high level of circulating pro-inflammatory cytokines might contribute to the distributive component of shock. Indeed, Kawasaki disease shock syndrome has been found associated with high levels of IL-6, C reactive protein, and procalicitonin [14]. In our series, we observed high levels of C reactive protein. This major pro-inflammatory state, together with multiorgan dysfunction, recently named paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection [15], might reflect a strong postviral immunological reaction to SARS-CoV-2 compared with other viral agents [16]. Of note, a cytokine storm syndrome with increased levels of inflammatory markers such as IL-6 was described in adults with covid-19[17,18]. Indeed, older age, higher D-dimer levels, lower haemoglobin and albumin levels, and more severe hyponatraemia were previously found to be associated with Kawasaki disease shock syndrome [19]. Gastrointestinal symptoms were also unusually common, affecting all of our 21 patients. A previous study reported intestinal pseudoobstruction in only 2% of 310 patients with Kawasaki disease[20]. As previously described, other symptoms of Kawasaki disease appeared after the intestinal ones in all patients, which could have led to diagnostic and therapeutic delays in some children [21]. In multisystem inflammatory syndrome, imminent treatment with intravenous immunoglobulins is associated with a beneficial outcome. In our cases, swift improvement with IVIG alone

Conclusion

This report may serve as a useful reference to other clinicians caring for pediatric patients affected by COVID-19 as understanding of the clinical presentation patterns continue to evolve. Further description of the clinical course of pediatric patients diagnosed with COVID-19 remains necessary, particularly regarding the potential association with KD.

Consent:

Written informed consent was obtained from the patient for publication of this case report.

Disclosure:

This clinical case was written based on clinical observation without any funding.

Conflicts of interest:

There are no conflicts of interest between the authors and between the authors and the patient.