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.

Multisystem Inflammatory Syndrome in Children: Unique Disease or Part of the Kawasaki Disease Spectrum?

“…A feature that is pointed to as distinguishing MIS-C as a unique disease process vs. KD is that the median age of MIS-C cases was 9–10 years in the largest reported series ( 1 – 6 , 32 ), whereas KD occurs predominantly in children 5 years of age or younger and has a peak incidence at around 10 months of age ( 33 ). There are, however, several reasons that may explain why younger children are more spared than older children and adolescents by COVID-19, in general, and, as a consequence, also by MIS-C.…”

“…Of the 149 cases of inflammatory illness in children and adolescents registered in Italy between February and May 2020 ( 32 ), 96 met the AHA criteria for classic or incomplete KD, 10 met the same criteria plus the case definition for MIS-C, and another 43 only met only the case definition for MIS-C. The clinical diversities between patients with MIS-C and KD paralleled those observed in other series, and children with MIS-C tested positive for SARS-CoV-2 more frequently that those with KD.…”

Pediatric COVID-19: Immunopathogenesis, Transmission and Prevention

“…Clinically, children with MIS-C present more heterogeneous symptoms than classical KD, as most children present with persistent fever, systemic inflammation, shock and multiple organ involvement [ 68 ]. Gastrointestinal manifestations are observed in 50–80% of MIS-C cases, sometimes with features of acute abdominal pain.…”

Improving Coronavirus Disease Tracking in Malaysian Health System

“…The DOHMH also has an incident command system (ICS), which is different from the standard DOHMH structure in that it is an office wide structure for dealing with and responding to crises. The ICS is divided into 10 sectors and is led by an episode officer who reports directly to the Commissioner of Health [1] . DOHMH workers are allocated to an area inside the ICS and can be approached to help their endless supply of the framework.…”

“…oronavirus disease (COVID-19) is a newfound virus causing severe, intense respiratory disorder (coronavirus sickness COVID-19) [1] rose in Wuhan, Hubei Province, China, and quickly spread to different nations worldwide. At present, the Malaysian government and health center are trying their best to learn and stop the spread.…”