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Abstract Background Numerous studies described the epidemiological link and main clinical features of pediatric COVID-19, during the first pandemic period. Our study encompasses several different phases since the National Lockdown in Italy. The primary outcome is (I) to analyze the prevalence of positive NST (Nasopharyngeal Swab Test) among the largest Italian Pediatric cohort admitted to a single regional PED Hub for COVID-19 during an eight-month period. Secondary outcomes are: (II) the description of trend of admissions in our PED and (III) the categorization of the positive patients according to clinical manifestations and epidemiological link. Methods We described 316 patients with a positive NST for SARS-CoV2, on a total of 5001 nasopharyngeal swabs performed among 13,171 admissions at our PED, over a period starting from March 17th, 2020 to December 1st, 2020. Age, epidemiological link, clinical features and hospitalizations were analyzed according to different lockdown phases. Data were collected anonymously from electronic records and analyzed using SPSS 22.00 statistics software (Chicago, IL). Results Thirty-six percent of total admissions have been tested. During the post lockdown period, we performed the highest percentage of NST (Nasopharyngeal Swab Test) 49.7%, and among them 7.9% were positive. The prevalence of infection during a 10-month period was 2.3%. Mean age was 6.5 years old. Familial Link accounted for the 67.7% of infection, while Extrafamilial and Unknown link accounted for 17 and 14.9%, respectively. Familial link is predominant during all phases. Seventeen patients showed an intra-scholastic link, and the highest prevalence was observed in the 7–10 years age group, with a prevalence of 12.8% (5 patients). Fever was the most frequent symptom (66%), in particular among preschooler children aged 0–6 years (71.9%). Older children were more frequently symptomatic. Seven patients were admitted with MIS-C diagnosis. Conclusions Different levels of containment measures caused important changes in number of positive NST for SARS-CoV2. Familial link was predominant in our cohort, during all phases of Lockdown. The risk of being infected at home is four time greater than the risk of being infected from an extra familial individual. Further studies are needed to evaluate the clear impact of intra-scholastic link. The constant improvement in knowledge on onset symptoms and risk factor for SARS-CoV2 infection and its complications (e.g. MIS-C), can impact on number of hospitalizations, ICU admissions and early management.

[This corrects the article DOI: 10.1371/journal.pone.0157962.].

AIMS/HYPOTHESIS:Although numerous environmental agents have been investigated over the years as possible triggers of type 1 diabetes (T1D), its causes remain unclear. We have already demonstrated an increased prevalence of antibodies against peptides derived from Mycobacterium avuim subsp. paratuberculosis (MAP) homologous to human zinc transporter 8 protein (ZnT8) and proinsulin in Italian subjects at risk for or affected by T1D. In this study, we compared titers of the previously detected antibodies with seroreactivity to MAP lipopentapetide (L5P) that recently emerged as a strong immunogenic component able to specifically distinguish MAP from other mycobacteria. METHODS:Plasma of 32 children and youth at risk for T1D including follow-up samples and 42 age-matched healthy controls (HC) recruited at the Tor Vergata University Hospital in Rome was analyzed by indirect ELISA for the presence of antibodies against MAP-derived epitopes MAP3865c133-141, MAP3865c125-133, MAP2404c70-85 and MAP1,4αgbp157-173 along with their ZnT8 and proinsulin homologs. The data were analyzed through two-tailed Mann-Whitney U test and relation between variables was determined by principal component analysis. RESULTS:Responses to L5P were not detectable in subjects whose initial seroreactivity to MAP peptides and their human homologs was lost in follow-up samples, whereas anti-L5P antibodies appeared constantly in individuals with a stable immunity against MAP antigens. The overall coincidence in positivity to L5P and the four MAP epitopes both in children at risk for T1D and HC exceeded 90%. CONCLUSIONS:MAP-derived homologs may cross-react with ZnT8 and proinsulin peptides inducing immune responses at a young age in subjects predisposed for T1D. Thus, L5P may have a diagnostic value to immediately indicate the presence of anti-MAP seroreactivity when evaluation of a more complex antibody status is not required. Almost complete coincidence in responses to both types of antigens lends support to the involvement of MAP in T1D.

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne’s disease in ruminants. Recent studies have linked MAP to type 1 diabetes (T1D) in the Sardinian population. The aim of this study was to investigate the prevalence of MAP infection in a T1D cohort from continental Italy compared with healthy control subjects. 247 T1D subjects and 110 healthy controls were tested for the presence of MAP. MAP DNA was detected using IS900-specific polymerase chain reaction (PCR). The presence of antibodies towards a MAP antigen, heparin binding hemoagglutinin (HBHA), was detected by ELISA. We demonstrated a higher MAP DNA prevalence in plasma samples from T1D patients and a stronger immune response towards MAP HBHA, compared with healthy control subjects. Moreover, in the recent onset patients, we observed an association between anti-MAP antibodies and HLA DQ2 (DQA1 0201/DQB1 0202). These findings taken together support the hypothesis of MAP as an environmental risk factor for the development of T1D in genetically predisposed subjects, probably involving a mechanism of molecular mimicry between MAP antigens and pancreatic islet β-cells.