Multisystem inammatory syndrome with features of Atypical Kawasaki disease during COVID-19 pandemic: Report of a case from India

There is a global concern of increasing number of children presenting with inammatory syndrome with clinical features simulating Kawasaki disease, during ongoing COVID-19 pandemic. We report a very similar case of 5-year-old boy from a COVID-19 hotspot area in Kerala state of India who presented in late April 2020 with acute febrile illness with abdominal pain and loose stools followed by shock. On examination, child had bulbar conjunctivitis and extremity edema. Initial investigations showed high inammatory parameters, elevated serum creatinine and liver enzymes. Echocardiography showed moderate LV dysfunction and normal coronaries. Cardiac enzymes were also elevated, suggesting myocarditis. He was treated with inotropic support, respiratory support with High Flow Nasal Cannula, IV Immunoglobulins, aspirin, steroids and diuretics. RT PCR for SARS-CoV-2 was negative twice. His clinical condition improved rapidly, was afebrile from day 2, inammatory parameters decreased, left ventricular function improved and was discharged after 6 days of hospital stay.


Introduction
Kawasaki disease (KD) is the most common systemic vasculitis in children, predominantly affecting the medium sized and small vessels [1]. The exact etiology of KD being not clear, it is believed that some infectious agent can trigger clinically apparent disease in individuals with certain genetic predisposition [2].
COVID-19 infection in children is less severe and has lesser mortality, compared to adults. However, National Health System (NHS) of United Kingdom and Pediatric Intensive Care Society (PICS) issued an alert recently regarding occurrence of around 20 cases of so called Paediatric multisystem in ammatory syndrome temporally associated with COVID-19 [3]. This syndrome shared overlapping features with other paediatric in ammatory conditions like KD and toxic shock syndromes. We report a very similar case of 5-year-old boy from a COVID infection hotspot area in Kerala state of India who presented in April 2020 with multi organ dysfunction.

Case Report
A previously well 5-year-old child presented with acute febrile illness without any obvious foci. On day 3 of illness, a urine routine examination showed pyuria and he was started on oral antibiotics. He continued to have high grade fever spikes and developed severe crampy abdominal pain with loose stools on day 5.
2D Echocardiogram revealed global left ventricular hypokinesia with moderate systolic dysfunction (ejection fraction-35 %) and normal coronaries (RCA and LMCA at +1.5 Z score, LAD +1.7 Z score). Chest Xray showed cardiomegaly ( Figure 1) and cardiac enzymes (HS Troponin I-29 ng/L (0-19), proBNP-8000 pg/ml) were elevated, suggesting myocarditis. Inotropic support with adrenaline was started and respiratory support with High Flow Nasal Cannula (HFNC) 2 litre/kg ow was initiated. Intravenous antibiotic-ceftriaxone was also started. Overall constellation of clinical features (sterile pyuria, bulbar conjunctivitis, extremity edema, elevated ESR and CRP, hypoalbuminemia, myocarditis) suggested atypical KD. IV immunoglobulins 2g/kg was given over 18 hours. In view of symptomatic myocarditis in KD, methyl prednisolone pulse (30mg/kg/day for 3 days) was also given. Diuretics for preload reduction, enalapril for afterload reduction and remodelling were also started. done to nd any other viral etiology was also negative. Child was discharged on day 6 of hospital stay on anti-thrombotic dose of aspirin, maintenance dose of oral steroids and low dose enalapril.

Discussion
There is a growing global concern that a SARS-CoV-2 related in ammatory syndrome is emerging in children. Clusters of children from UK with this in ammatory syndrome had acute febrile illness with evidence of single or multi-organ dysfunction. Laboratory features were neutrophilia, elevated CRP and clinical features included abdominal pain, gastrointestinal symptoms, myocarditis and shock [4]. Our case also had almost similar laboratory parameters and clinical pro le.

Multiple infectious triggers like adenovirus and coronavirus (New Haven coronavirus) have been
inconclusively associated with KD in past [5,6]. In the cluster of cases from UK, common microbial causes were excluded and SARS-CoV-2 PCR testing was positive in few cases, while serological tests (possible preceding SARS-CoV-2 infection ) were positive in some cases. In our case, RT PCR was negative on two occasions. Our patient hailed from a COVID hotspot area and his father had returned from an endemic foreign country 2 months back. Hence, past asymptomatic infection in the child was a possibility. Antibody tests could not be done due to the unavailability.
A diagnosis of "atypical" KD is made in patients presenting with atypical or unusual clinical features.
Though some evidence of myocarditis has been seen in more than 50 % patients in the acute phase of KD, symptomatic myocarditis with cardiogenic shock is rare [7]. Available reports of such cases suggested IVIG resistance and good response to pulse steroid therapy [8].As our patient's hemodynamic condition was deteriorating, we used steroids from day 1 itself. There was considerable improvement in left ventricular systolic function, and we could reduce inotropic support and avoid invasive ventilation.
There could be different explanations for the possible association of COVID infection and KD. In PCR negative-antibody positive cases, it's quite possible that corona virus infection in recent past can trigger an immune response simulating KD. COVID-19 is also known to cause excessive in ammation and cytokine storm like KD, during active infective phase. Similar alert regarding a mysterious in ammatory syndrome in children is now reported from USA also [9,10]. To the best of our knowledge, ours is the rst report from India about multi-system in ammatory syndrome simulating atypical KD during this pandemic. As of now, the association between COVID infection and KD is not conclusively proven.
However, as similar reports have come from various countries with temporal relation to COVID infection in the community, general paediatricians need to be aware of such atypical presentations and early referral to tertiary care needs to be undertaken.

Declarations
Funding -No funding from any source was involved in the research or development of manuscript.
Con icts of interest -None of the authors have any real or perceived con ict of interests with respect to research, authorship, and/or publication of this article.
Ethical approval from Institute Ethics committee was obtained Consent to participate -Obtained from parents. Consent for publication -Consent for publication obtained from Parents (patient was a 5 year old kid). Figure 1 Chest X-rays of child on day 1 and day 5. Note the cardiomegaly with left ventricular dilatation on day 1, which improved by day 5.