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

Biochronology and palaeoenvironmental changes from the Middle Pliocene to the Late Pleistocene in Central Italy

Paleoenvironmental variations that occurred in Italy from the Middle Pliocene to the Late Pleistocene are described. The number of large mammal species seems increased moderately, especially from the Galerian to the Late Aurelian biochronological units. On the contrary, the paleobotanical data show a decrease of the forest cover from the Middle Pliocene to the late Early Pleistocene and an increase of lands occupied by prairies and steppes. This change is also supported by the appearance of hypsodont taxa among mammals. The distribution of mammal faunas between the Adriatic and Tyrrhenian sides of Central Italy, during the Middle and Late Pleistocene, seems not to be influenced by climatic and environment differences. When the Adriatic data are more complete, it is possible, in fact, to observe a trend that is fairly close to that of the Tyrrhenian. The majority of megaherbivorous taxa has an Asian origin, and it can be hypothesized that in the interglacial phases, the Tosco-Emilian Apennines allowed the taxa coming from the northeast to enter and spread out into the more diversified Tyrrhenian side, whereas during the glacial periods the narrow Ligurian corridor were followed. This research supports the role of the Italian Peninsula as a refuge area for continental Europe; this particular condition permits the Italian mammal faunas to develop endemic lineage (such as Elephas antiquus italicus Osborn, 1931, Cervus elaphus rianensis Leonardi & Petronio, 1974, C. e. aretinus Azzaroli, 1947, etc.). At last, biodiversity sharply dropped during the last 30 000 years, probably due to the anthropic activities and the strong climatic cooling of the last pleniglacial