COVID-19 Positive Versus Negative Complete Kawasaki Disease: A Study from the International Kawasaki Disease Registry

Abstract

To determine clinical differences for children with complete Kawasaki disease (KD) with and without evidence of preceding SARS-CoV-2 infection. From January 2020, contemporaneous patients with complete KD criteria were classified as either SARS-CoV-2 positive (KDCOVID+; confirmed household exposure, positive PCR and/or serology) or SARS-CoV-2 negative (KDCOVID−; negative testing and no exposure) and compared. Of 744 patients in the International Kawasaki Disease Registry, 52 were KDCOVID− and 61 were KDCOVID+. KDCOVID+ patients were older (median 5.5 vs. 3.7 years; p < 0.001), and all additionally met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C). They were more likely to have abdominal pain (60% vs. 35%; p = 0.008) and headache (38% vs. 10%; p < 0.001) and had significantly higher CRP, troponin, and BUN/creatinine, and lower hemoglobin, platelets, and lymphocytes. KDCOVID+ patients were more likely to have shock (41% vs. 6%; p < 0.001), ICU admission (62% vs. 10%; p < 0.001), lower left ventricular ejection fraction (mean lowest LVEF 53% vs. 60%; p < 0.001), and to have received inotropic support (60% vs. 10%; p < 0.001). Both groups received IVIG (2 doses in 22% vs. 18%; p = 0.63), but KDCOVID+ were more likely to have received steroids (85% vs. 35%; p < 0.001) and anakinra (60% vs. 10%; p = 0.002). KDCOVID− patients were more likely to have medium/large coronary artery aneurysms (CAA, 12% vs. 0%; p = 0.01). KDCOVID+ patients differ from KDCOVID−, have more severe disease, and greater evidence of myocardial involvement and cardiovascular dysfunction rather than CAA. These patients may be a distinct KD phenotype in the presence of a prevalent specific trigger.

Obesity and Outcomes of Kawasaki Disease and COVID-19–Related Multisystem Inflammatory Syndrome in Children

“…Patients with KD, however, had a higher mean maximal coronary artery z score than those with MIS-C. These findings are similar to earlier work from our group of investigators that compared SARS-CoV-2–positive patients with KD (presumed MIS-C with a KD-like presentation) with confirmed SARS-CoV-2–negative patients with KD . Moreover, the severity of presentation, multiorgan involvement, and need for ICU care for patients with MIS-C has been reported by other investigators …”

“…These findings are similar to earlier work from our group of investigators that compared SARS-CoV-2-positive patients with KD (presumed MIS-C with a KD-like presentation) with confirmed SARS-CoV-2-negative patients with KD. 21 Moreover, the severity of presentation, multiorgan involvement, and need for ICU care for patients with MIS-C has been reported by other investigators. 2,5 In the present study, in patients with KD, obesity was not associated with clinical outcomes apart from ICU admission rates.…”

“…First, we excluded patients who met the criteria for KD but had either an unknown or positive COVID-19 infectious status. This stringent criterion may have excluded some true KD cases; however, this approach was necessary to avoid misclassification, given the clinical overlap between KD and MIS-C. To this end, earlier work from the IKDR has reported that COVID-positive patients with KD had a tendency toward a demographic and clinical profile suggestive of MIS-C. 21 As a result, 499 potential patients with KD were excluded from the analysis, thus potentially limiting the power of our analysis. Moreover, several variables had missing data, particularly for patients with KD, which is likely because these variables are not commonly collected in the clinical setting (eg, NT-proBNP and troponin I).…”

“…This study and report followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies . The IKDR enrolled contemporaneous patients (as of January 2020) with acute KD and MIS-C, and patients with cardiac complications secondary to acute COVID-19 from 42 sites and 8 countries . Data were abstracted from medical records at each participating site, including patient demographic characteristics, clinical features, disease course (including COVID-19 testing status, serial laboratory test values, and cardiac imaging reports), as well as management and clinical outcomes (including admission to the ICU, medications used, and death).…”