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Kawasaki disease and COVID-19


The rapid spread of Coronavirus disease 2019 ( COVID-19 ) caused by severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) has led to a global pandemic, with infected individuals of all ages residing in almost every country in the world.
The pediatric population appears to be affected in much smaller proportions than adults, with only 2% of cases described in patients under age 20.

An epidemiologic report has described 731 confirmed COVID-19 cases in the pediatric population, with over 90% of patients characterized as asymptomatic, mild, or moderate cases.
This study looked at a total of 2143 patients, 1412 of whom had suspected but unconfirmed COVID-19 infection, but there was little description of co-incidence of other clinical conditions, and no cases reported of concurrent Kawasaki disease ( KD ).

Researchers have described the case of a pediatric patient diagnosed and treated for classic Kawasaki disease in the setting of confirmed COVID-19 infection.

Case description

The patient is a 6-month-old, full term, previously healthy and fully immunized female who initially presented to pediatric urgent care with one day of fever, fussiness, and refusal to eat. She did not exhibit cough, congestion or rhinorrhea.
Examination showed a fussy infant with a temperature of 38.8°C, with no focal signs of infection.
Laboratory evaluation included a rapid influenza swab and a catheterized urinalysis with urine culture, all of which were negative.
She was diagnosed with a viral infection.

On day 2 of fever, she developed an erythematous, seemingly non-pruritic, blotchy rash.

She re-presented to urgent care on day 4 of fever with persistent rash. Although she remained free of cough, there was possible mild congestion.
Vital signs showed temperature of 38.3°C, sinus tachycardia ( 200 beats/minute ), and tachypnea with an oxygen saturation of 100%.
Examination was notable for irritability, limbic-sparing conjunctivitis, and dry cracked lips.
There was no appreciable lymphadenopathy and at the time she had normal extremities.
She had mild subcostal retractions, though normal breath sounds.
Laboratory testing showed a left-shifted white blood cell count with bandemia, normocytic anemia, normal platelets, markedly elevated C-reactive protein 13.3 mg/dL, and erythrocyte sedimentation rate 118 mm/hr. She had hyponatremia ( sodium 133 mEq/L ) and hypoalbuminemia ( albumin 2.8 g/dL ), with otherwise normal chemistries including liver function tests.
Respiratory pathogen testing by reverse transcription polymerase chain reaction test ( RT-PCR ) and blood culture were negative.
A chest x-ray showed a faint opacity in the left midlung zone.

Throughout this period of illness, she had no sick contacts. Her 9-year-old sibling had upper respiratory symptoms 3 weeks prior.
The family had self-isolated due to the COVID-19 pandemic for the week prior, without leaving home for school or work.
There was no history of recent travel.

The patient was referred for admission for Kawasaki disease evaluation. Given fever, possible mild congestion, and chest x-ray findings, she was sent to the emergency department for COVID-19 testing prior to admission to the pediatric floor.
Upon arrival, the patient was on day 5 of fever, had limbic sparing conjunctivitis, prominent tongue papilla, a blanching, polymorphous, maculopapular rash, and swelling of the hands and lower extremities, thus meeting classic criteria for Kawasaki disease.
She was treated with a single dose of 2 g/kg intravenous immunoglobulin ( IVIG ) and high dose Acetylsalicylic acid ( ASA 20mg/kg four times daily ) according to treatment guidelines.
Her last elevated temperature was 38.3°C just after completing IVIG.
An echocardiogram was normal without any evidence of coronary dilation or aneurysm, no pericardial effusion, and with normal valvar and ventricular function.

The evening prior to discharge, RT-PCR testing for COVID-19 resulted positive from the Stanford Clinical Virology Laboratory.
The Public Health Department was notified, and the family was instructed to quarantine at home for 14 days from positive test date.
She was discharged on low dose ASA ( 3mg/kg daily ) with plans to follow-up with pediatric cardiology for repeat echocardiographic evaluation two weeks after discharge, timed to occur after the mandated 14-day quarantine.

Discussion

This is the first described case of Kawasaki disease with concurrent COVID-19 infection.

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 less than 2 years of age, and 80% in those less than 5 years of age.

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.
The cause of Kawasaki disease remains unknown, despite several decades of investigation. Some evidence suggests an infectious trigger, with winter-spring seasonality of the disease, and wave-like spread of Japanese epidemics of Kawasaki disease.

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.

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.

To date, the most common pediatric presentation of COVID-19 is an array of signs and symptoms including completely asymptomatic to symptoms of acute upper respiratory tract infection such as fever, fatigue, cough, sore throat, rhinorrhea and congestion, and shortness of breath.
In more severe cases, symptoms can include gastrointestinal symptoms and patients can progress to respiratory failure, shock, coagulation dysfunction, and renal injury. ( Xagena )

Jones VG, Mills M, Suarez D, et al. COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatr 2020

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