Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Abstract

Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities.

Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups.

Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data.

Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

Keywords: Coronary artery abnormalities; Hypotension; Kawasaki disease; Multisystem inflammatory syndrome associated with coronavirus disease; Myocarditis; Pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection; SARS-CoV-2.

Fig. 1

Enrollment of patients flow chart. One hundred fifty-nine patients were initially enrolled; 10 were then excluded form expert panel revision. Ninety-six patients fitted KD or iKD diagnosis. Ten patients fitted both KD/iKD or Kawacovid criteria while 43 patients filled Kawacovid criteria. KD=Kawasaki Disease; iKD = incomplete Kawasaki Disease

Fig. 2

SARS-CoV-2 infection and KD/KawaCOVID patients in Italy. Distribution of KDG patients (blue numbers) and KCG (green numbers) in different areas per SARS-CoV-2 incidence (right squares indicate SARS-CoV-2 number of patients/general population). KDG = Kawasaki Disease Group; KCG = KawaCOVID Group

Fig. 3

Trend of clinical manifestations among the KawaCOVID Group (KCG) and the Kawasaki Disease Group (KDG)

Fig. 4

Relationship between SARS-CoV-2 infection trend and new cases of Kawasaki Disease and KawaCOVID during SARS-CoV-2 infection in Italy from February 1st 2020 to May 31st 2020