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

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

Pancreatic development in newborn guinea pigs fed intact or low-hydrolyzed protein formulas

Aim: To evaluate pancreatic development in newborn guinea pigs fed since birth intact or low-hydrolyzed protein formulas compared with breast milk.Methods: Forty-five newborn guinea pigs were allocated to three feeding regimens: breast milk (n = 15) and two isocaloric isonitrogen milk formulas containing intact (n = 15) or low-hydrolyzed proteins (n = 15). Body weight and food consumption were recorded every day. After 8 days, one third of pups from each group was killed, and the remaining animals were weaned. Another third was killed on day 14, and the remainders were killed on day 20. Zymogen storage was evaluated on pancreatic sections, whereas DNA and RNA concentrations were measured by a fluorometric method.Results: Compared with breast fed pups, both groups of artificially fed animals showed lower weight gain during the first 2 weeks of life but not after weaning. Both formulas fed groups had significantly lower amount of zymogen granules in pancreatic acinar cells at 8 and 14 days of life. This reduction was still present at day 20 in intact protein formula but not in low-hydrolyzed protein formula fed animals in which higher RNA/DNA ratio was also observed compared with breast fed pups.Conclusion: In newborn guinea pigs, artificial feeding is associated with reduced zymogen storage at days 8 and 14 of life. After weaning, cellular content of zymogen granules is comparable with breast fed pups only in low-hydrolyzed protein formula fed animals, even in the presence of some evidence of pancreatic hypoplasia