There are growing evidence of clinical manifestations other than acute respiratory syndrome in severe acute respiratory syndrome associated with coronavirus 2-infected children. In our multicenter retrospective analysis, we observed among 127 severe acute respiratory syndrome associated with coronavirus 2 positive children that the presence of gastrointestinal symptoms was more frequently associated with severe and critical phenotype (P = 0.029). Moreover, having gastrointestinal symptoms was more frequently reported in patients who developed cardiac impairment.

To assess whether the use of the revised Cochrane risk of bias tool for randomized trials (RoB2) in systematic reviews (SRs) adheres to RoB2 guidance. We searched MEDLINE, Embase, Cochrane Library from 2019 to May 2021 to identify SRs using RoB2. We analyzed methods and results sections to see whether risk of bias was assessed at outcome measure level and applied to primary outcomes of the SR as per RoB2 guidance. The relation between SR characteristics and adequacy of RoB2 use was examined by logistic regression analysis. Two hundred-eight SRs were included. We could assess adherence in 137 SRs as 12 declared using RoB2 but actually used RoB1 and 59 did not report the number of primary outcomes. The tool usage was adherent in 69.3% SRs. Considering SRs with multiple primary outcomes, adherence dropped to 28.8%. We found a positive association between RoB2 guidance adherence and the methodological quality of the reviews assessed by AMSTAR2 (p-for-trend 0.007). Multivariable regression analysis suggested journal impact factor [first quartile vs. other quartiles] was associated with RoB2 adherence (OR 0.34; 95% CI: 0.16-0.72). Many SRs did not adhere to RoB2 guidance as they applied the tool at the study level rather than at the outcome measure level. Lack of adherence was more likely among low and very low quality reviews.

Vitamin D and omega 3 fatty acid (ω-3) co-supplementation potentially improves type 1 diabetes (T1D) by attenuating autoimmunity and counteracting inflammation. This cohort study, preliminary to a randomized control trial (RCT), is aimed at evaluating, in a series of T1D children assuming Mediterranean diet and an intake of cholecalciferol of 1000U/day from T1D onset, if ω-3 co-supplementation preserves the residual endogen insulin secretion (REIS). Therefore, the cohort of 22 “new onsets” of 2017 received ω-3 (eicosapentenoic acid (EPA) plus docosahexaenoic acid (DHA), 60 mg/kg/day), and were compared retrospectively vs. the 37 “previous onsets” without ω-3 supplementation. Glicosilated hemoglobin (HbA1c%), the daily insulin demand (IU/Kg/day) and IDAA1c, a composite index (calculated as IU/Kg/day × 4 + HbA1c%), as surrogates of REIS, were evaluated at recruitment (T0) and 12 months later (T12). In the ω-3 supplemented group, dietary intakes were evaluated at T0 and T12. As an outcome, a decreased insulin demand (p < 0.01), particularly as pre-meal boluses (p < 0.01), and IDAA1c (p < 0.01), were found in the ω-3 supplemented group, while HbA1c% was not significantly different. Diet analysis in the ω-3 supplemented group, at T12 vs. T0, highlighted that the intake of arachidonic acid (AA) decreased (p < 0.01). At T0, the AA intake was inversely correlated with HbA1c% (p < 0.05; r;. 0.411). In conclusion, the results suggest that vitamin D plus ω-3 co-supplementation as well as AA reduction in the Mediterranean diet display benefits for T1D children at onset and deserve further investigation.

Severe acute respiratory syndrome coronavirus 2 infection in children mainly shows a milder course. In complicated cases, it is unknown whether inflammation is predictive of disease severity, as in adults. Moreover, cardiac involvement is anecdotally described. We report the case of a 2-month-old infant with severe acute respiratory syndrome coronavirus 2 infection presenting with fever, tachycardia and elevated interleukin-6, who was diagnosed with myocarditis and treated with immunoglobulins.

Objectives Vitamin D plays an immunoregulatory activity. The aim of this study was to assess the correlation between blood serum 25(OH)D levels and Th17 and Treg circulating subsets, mainly Treg/ICOS ⁺ which seems to have a protective role in autoimmunity, in children with T1D and their healthy siblings (S). The secondary aim was to evaluate the impact of vitamin D supplementation on these subsets. Patients and Methods 22 T1D and 33 S were enrolled. Glucose, HbA1c, 25(OH)D, Th17 (CD4 ⁺CCR6 ⁺), Treg (CD4 ⁺CD25 ⁺Foxp3 ⁺), and Treg/ICOS ⁺ cells were evaluated. According to HLA haplotypes, subjects were classified as “at risk” (HLA ⁺), "protective haplotypes" (HLA ^-; "nested controls"), and “undetermined” (HLA ^UND). T1D and S subjects were supplemented with cholecalciferol 1,000 IU/die and evaluated after 6 months. Results Vitamin D insufficiency (74.4 %) and deficiency (43%) were frequent. S subjects with 25(OH)D levels &25 nmol/L had Th17, Treg (p&0.01) and Treg/ICOS ⁺ (p&0.05) percentages higher than subjects with 25(OH)D >75 nmol/L. Treg/ICOS ⁺ percentages (p&0.05) were higher in HLA ^- S subjects compared to percentages observed in their siblings with T1D. At baseline, in S subjects, a decreasing trend in Th17 and Treg/ICOS ⁺ values (p&0.05) from vitamin D deficiency to sufficiency was observed; 25(OH)D levels were negative predictors of Treg/ICOS ⁺ (R-square: 0.301) and Th17 percentages (R-square: 0.138). After 6 months, supplemented S subjects showed higher 25(OH)D levels (p&0.0001), and lower Th17 (p&0.0001) and Treg/ICOS+ (p&0.05) percentages than at baseline; supplemented T1D patients only had a decrease in Th17 levels (p&0.05). Conclusion serum 25(OH)D levels seem to affect Th17 and Treg cell subsets in S subjects, consistent with its immunomodulating role. HLA role should be investigated in a larger population.

While the risk of SARS-CoV-2 infection and/or COVID-19 disease progression in the general population has been largely assessed, its impact on HIV-positive individuals remains unclear. We present clinical and immunological data collected in a cohort of HIV-infected young individuals during the first wave of COVID-19 pandemic. SARS-CoV-2 RNA, virus-specific antibodies, as well as the expression of factors involved in the anti-viral immune response were analyzed. Moreover, we set up an in vitro coinfection assay to study the mechanisms correlated to the coinfection process. Our results did not show any increased risk of severe COVID-19 in HIV-positive young individuals. In those subjects who contracted SARS-CoV-2 infection, an increase in IL-10 expression and production was observed. Furthermore, in the in vitro coinfection assay, we revealed a reduction in SARS-CoV-2 replication associated to an upregulation of IL-10. We speculate that IL-10 could play a crucial role in the course of SARS-CoV-2 infection in HIV-positive individuals. These results might help defining clinical management of HIV/SARS-CoV-2 co-infected young individuals, or putative indications for vaccination schedules in this population.