COVID-19 and Kawasaki Disease: Novel Virus and Novel Case

Discussion

To our knowledge, this is the first described case of KD with concurrent COVID-19 infection. KD 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” KD 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 KD remains unknown despite several decades of investigation. Some evidence suggests an infectious trigger, with winter to spring seasonality of the disease, and wavelike spread of Japanese epidemics of KD.⁴ In various studies, authors have described an association between viral respiratory infections and KD, ranging from 9% to as high as 42% of patients with KD testing positive for a respiratory viral infection in the 30 days leading up to diagnosis of KD.^5–7 Interestingly, Turnier et al⁵ in 2015 described that 28% of positive results were attributable to rhinovirus and/or enterovirus, and 8.7% were due to parainfluenza; results for the remaining pathogens (respiratory syncytial virus, influenza, adenovirus, and human coronavirus [strains 229E, HKU1, NL63, OC43]) were each positive <5% of the time.

Although the clinical significance of our patient’s positive COVID-19 test result in the setting of her KD is not clear, her testing for COVID-19 appears accurate. The Stanford Health Care Clinical Virology Laboratory serves pediatric and adult tertiary-care hospitals and affiliated clinics in northern California. In early January 2020, 2 multiplex RT-PCR assays were validated on the basis of a modified published protocol.⁸ These assays are used to target the envelope and RNA-dependent RNA-polymerase genes, respectively. Analytical sensitivity from nasopharyngeal swabs eluted in viral transport medium was shown to be good, with a lower limit of detection ranging between 500 and 700 copies per mL. Furthermore, analytical specificity was high, with no cross-reactivity observed in >50 tested samples with seasonal coronaviruses or other respiratory viruses. Samples revealing late cycle threshold values (cycle threshold ≥40) are repeated for confirmatory testing to prevent false-positive results. Although direct comparison data between this assay and the Centers for Disease Control and Prevention’s assay (which targets 2 regions of the nucleocapsid gene) have not yet been published, preliminary data suggest similar analytic performance.^8,9

At the time of this patient’s hospital discharge, the World Health Organization reported almost 180 000 global cases of confirmed COVID-19, with 7426 deaths.¹⁰ Despite the growing number of reported cases, there remains a knowledge gap regarding the infectious, epidemiological, and clinical features associated with COVID-19 illness, particularly in the pediatric population. 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.²

With regard to her COVID-19 infection, our patient’s clinical course and presentation were mild. Throughout her hospitalization, she did not have any notable respiratory symptoms, and repeat chest radiograph was not obtained. Her mother was in close contact with the infant throughout hospitalization and has no respiratory symptoms as of 2 weeks after hospital discharge. When coronary involvement appears with KD, it typically occurs after the initial presentation. As such, recommendations for monitoring include echocardiography in 1 to 2 weeks and 4 to 6 weeks after treatment.³

As we continue to see the spread of COVID-19 and increase in cases worldwide, clinical criteria for testing for COVID-19 may be restricted to those with respiratory symptoms because of constraints such as testing availability. In pediatrics, with the clinical spectrum yet to be clearly defined, patients presenting with fever alone or primarily with other organ system involvement such as gastrointestinal symptoms may be missed if testing is restricted to those with respiratory complaints alone.