Kawasaki Disease in the Time of COVID-19 and MIS-C: The International Kawasaki Disease Registry

Abstract

Background: Patients with multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) have overlapping clinical features. We compared demographics, clinical presentation, management, and outcomes of patients according to evidence of previous SARS-CoV-2 infection.

Methods: The International Kawasaki Disease Registry (IKDR) enrolled KD and MIS-C patients from sites in North, Central, and South America, Europe, Asia, and the Middle East. Evidence of previous infection was defined as: Positive (household contact or positive polymerase chain reaction [PCR]/serology), Possible (suggestive clinical features of MIS-C and/or KD with negative PCR or serology but not both), Negative (negative PCR and serology and no known exposure), and Unknown (incomplete testing and no known exposure).

Results: Of 2345 enrolled patients SARS-CoV-2 status was Positive for 1541 (66%) patients, Possible for 89 (4%), Negative for 404 (17%) and Unknown for 311 (13%). Clinical outcomes varied significantly among the groups, with more patients in the Positive/Possible groups presenting with shock, having admission to intensive care, receiving inotropic support, and having longer hospital stays. Regarding cardiac abnormalities, patients in the Positive/Possible groups had a higher prevalence of left ventricular dysfunction, and patients in the Negative and Unknown groups had more severe coronary artery abnormalities.

Conclusions: There appears to be a spectrum of clinical features from MIS-C to KD with a great deal of heterogeneity, and one primary differentiating factor is evidence for previous acute SARS-CoV-2 infection/exposure. SARS-CoV-2 Positive/Possible patients had more severe presentations and required more intensive management, with a greater likelihood of ventricular dysfunction but less severe coronary artery adverse outcomes, in keeping with MIS-C.

Graphical abstract

Figure 1

Number of Kawasaki Disease Clinical Features by SARS-CoV-2 Status Abbreviations: SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.Patients were stratified by SARS-CoV-2 infection status into four groups: Positive if the patient had a confirmed household contact within the 4 weeks prior to the onset of symptoms and/or positive test, either polymerase chain reaction (PCR), serology or both, Possible if the patient had suggestive clinical features of MIS-C and/or KD with absent household contact but with only one negative test, either PCR or serology but not both, Negative if the patient had no exposure and had negative PCR and negative serology, and Unknown if the patient had no known exposure and the PCR and serology testing were not performed.

Figure 2

Lowest Left Ventricular Ejection Fraction (%) by SARS-CoV-2 Status Abbreviations: SARS-CoV-2: severe acute respiratory syndrome coronavirus 2, LV: Left ventricle.Patients were stratified by SARS-CoV-2 infection status into four groups: Positive if the patient had a confirmed household contact within the 4 weeks prior to the onset of symptoms and/or positive test, either polymerase chain reaction (PCR), serology or both, Possible if the patient had suggestive clinical features of MIS-C and/or KD with absent household contact but with only one negative test, either PCR or serology but not both, Negative if the patient had no exposure and had negative PCR and negative serology, and Unknown if the patient had no known exposure and the PCR and serology testing were not performed.

Figure 3

Coronary Artery z-Score Category by SARS-CoV-2 Status Abbreviations: SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.The largest z score of any branch at any time was used, and categorized as “normal” (z score <2), “dilated” (z score 2 to <2.5), “small aneurysm” (z score 2.5 to <5), “medium aneurysm” (z score 5 to <10), and/or “large aneurysm” (>8 mm in diameter, or zscore >10)..Patients were stratified by SARS-CoV-2 infection status into four groups: Positive if the patient had a confirmed household contact within the 4 weeks prior to the onset of symptoms and/or positive test, either polymerase chain reaction (PCR), serology or both, Possible if the patient had suggestive clinical features of MIS-C and/or KD with absent household contact but with only one negative test, either PCR or serology but not both, Negative if the patient had no exposure and had negative PCR and negative serology, and Unknown if the patient had no known exposure and the PCR and serology testing were not performed.