Strongyloides stercoralis Infestation in a Child: How a Nematode Can Affect Gut Microbiota.

Background: Strongyloidiasis is a neglected tropical disease caused by the intestinal nematode Strongyloides stercoralis and characterized by gastrointestinal and pulmonary involvement. We report a pediatric case of strongyloidiasis to underline the response of the host microbiota to the perturbation induced by the nematode. Methods: We performed a 16S rRNA-metagenomic analysis of the gut microbiota of a 7-year-old female during and after S. stercolaris infection, investigating three time-point of stool samples' ecology: T0- during parasite infection, T1- a month after parasite infection, and T2- two months after parasite infection. Targeted-metagenomics were used to investigate ecology and to predict the functional pathways of the gut microbiota. Results: an increase in the alpha-diversity indices in T0-T1 samples was observed compared to T2 and healthy controls (CTRLs). Beta-diversity analysis showed a shift in the relative abundance of specific gut bacterial species from T0 to T2 samples. Moreover, the functional prediction of the targeted-metagenomics profiles suggested an enrichment of microbial glycan and carbohydrate metabolisms in the T0 sample compared with CTRLs. Conclusions: The herein report reinforces the literature suggestion of a putative direct or immune-mediated ability of S. stercolaris to promote the increase in bacterial diversity.

Food security and the nutritional status of children in foster care: new horizons in the protection of a fragile population.

BACKGROUND: The nutritional status of foster children, the quality of daily menus in group homes and the Food Security inside these organizations have been poorly studied and this study means to investigate them. METHODS: A sample of 125 children, ranging in age from 0-17 years, among seven group homes (group A) was compared with 121 children of the general population we (group B). To evaluate nutritional status, BMI percentiles were used. Mean percentiles of both groups were compared through statistical analysis. Both nutritional and caloric daily distributions in each organization were obtained using the 24-hour recall method. A specific questionnaire was administered to evaluate Food Security. RESULTS: From the analysis of mean BMI-for-age (or height-for-length) percentiles, did not observe statistically significant differences between group A and group B. The average daily nutrient and calorie distribution in group homes proves to be nearly optimal with the exception of a slight excess in proteins and a slight deficiency in PUFAs. Moreover, a low intake of iron and calcium was revealed. All organizations obtained a "High Food Security" profile. CONCLUSIONS: Nutritional conditions of foster children are no worse than that of children of the general population. Foster care provides the necessary conditions to support their growth.

Challenging diagnosis of congenital malaria in non-endemic areas.

BACKGROUND: Congenital malaria is usually defined as the detection of asexual forms of Plasmodium spp. in a blood sample of a neonate during perinatal age if there is no possibility of postpartum infection by a mosquito bite. The incidence of congenital malaria is highly variable and seems related to several factors, such as different diagnostic methods for Plasmodium spp. detection, and area in which the epidemiologic analyses are performed. In non-endemic countries, cases of congenital malaria are rare. Hereby, a case of a congenital malaria in an HIV exposed child is reported. CASE PRESENTATION: A 2-month-old male child was admitted to Bambino Gesù Children's Hospital due to anaemia and exposure to HIV. He was born prematurely in Italy by cesarean section at 34 weeks' gestation after a bicorial, biamniotic pregnancy by a migrant woman from Nigeria. He was the first of non-identical twins. Combined with anaemia, spleen and liver enlargement was noted, malaria was hypothesized. Malaria laboratory panel was performed on the newborn, mother and other twin blood samples, as follows: (i) malaria rapid diagnostic test (RDT); (ii) Giemsa-stained thick and thin blood smears for Plasmodium spp. identification and parasitaemia titration; (iii) molecular screening and typing of Plasmodium spp. by multiplex qualitative PCR assay based on 18S rRNA gene. Genotyping of Plasmodium falciparum isolates from mother and child was performed by neutral microsatellite and highly polymorphic marker amplification. CONCLUSIONS: The maternal RDT sample was negative, while the infant RDT was positive; in both cases microscopy of blood smears and PCR showed infection with P. falciparum. Two of the genotypic molecular markers displayed different allelic variants between the two samples. This difference could imply infection multiplicity of the mother during the pregnancy, possibly harbouring more than one isolate, only one of them being transmitted to the newborn while the other persisting in the mother's blood. Because of the increasing number of pregnant women coming from endemic areas for malaria, an accurate anamnesis of infant's mother, and the inclusion of Plasmodium spp. research into TORCH screenings for mother-infant pair at birth, aiming at reducing morbidity and mortality associated to the disease might be suitable.

Immunization status of children in foster homes: the first Italian data.

BACKGROUND: The aim of this paper was to evaluate vaccination coverage among children living in forest homes. METHODS: Data come from pediatric evaluation of a sample of children in group-homes in Rome, between September 2011 and April 2012, and compared vs. general population group. RESULTS: As for About children in foster homes it was found that 91/112 children (81.2%) had the vaccine coverage for all vaccines that compose the hexavalent (diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b) vaccine; 88/112 (78.6%) have been vaccinated for measles-mumps-rubella; 10/112 (8.9%) were vaccinated with meningococcal vaccine; 15/112 (13.4%) have been vaccinated with vaccine antipneumococcal. The data compared with general population showed a difference between the two groups (P<0.0001). CONCLUSION: The vaccination status is an important gauge to evaluate the quality of assistance in children in the general population and more than in this vulnerable group of children.

The pediatric gut bacteriome and virome in response to SARS-CoV-2 infection.

Introduction: Since the beginning of the SARS-CoV-2 pandemic in early 2020, it has been apparent that children were partially protected from both infection and the more severe forms of the disease. Many different mechanisms have been proposed to explain this phenomenon, including children's frequent exposure to other upper respiratory infections and vaccines, and which inflammatory cytokines they are more likely to produce in response to infection. Furthermore, given the presence of SARS-CoV-2 in the intestine and its ability to infect enterocytes, combined with the well described immunomodulatory capabilities of the microbiome, another potential contributing factor may be the presence of certain protective microbial members of the gut microbiota (GM). Methods: We performed shotgun metagenomic sequencing and profiled both the bacteriome and virome of the GM of pediatric SARS-CoV-2 patients compared to healthy, age-matched subjects. Results: We found that, while pediatric patients do share some pro-inflammatory microbial signatures with adult patients, they also possess a distinct microbial signature of protective bacteria previously found to be negatively correlated with SARS-CoV-2 infectivity and COVID-19 severity. COVID-19 was also associated with higher fecal Cytomegalovirus load, and with shifts in the relative abundances of bacteriophages in the GM. Furthermore, we address how the preventative treatment of COVID-19 patients with antibiotics, a common practice especially in the early days of the pandemic, affected the bacteriome and virome, as well as the abundances of antimicrobial resistance and virulence genes in these patients. Discussion: To our knowledge, this is the first study to address the bacteriome, virome, and resistome of pediatric patients in response to COVID-19 and to preventative antibiotics use.

Molecular characterization of SARS-CoV-2 Omicron clade and clinical presentation in children.

Since its emergence, SARS-CoV-2 Omicron clade has shown a marked degree of variability and different clinical presentation compared with previous clades. Here we demonstrate that at least four Omicron lineages circulated in children since December 2021, and studied until November 2022: BA.1 (33.6%), BA.2 (40.6%), BA.5 (23.7%) and BQ.1 (2.1%). At least 70% of infections concerned children under 1 year, most of them being infected with BA.2 lineages (n = 201, 75.6%). Looking at SARS-CoV-2 genetic variability, 69 SNPs were found to be significantly associated in pairs, (phi < - 0.3 or > 0.3 and p-value < 0.001). 16 SNPs were involved in 4 distinct clusters (bootstrap > 0.75). One of these clusters (A23040G, A27259C, T23617G, T23620G) was also positively associated with moderate/severe COVID-19 presentation (AOR [95% CI] 2.49 [1.26-4.89] p-value: 0.008) together with comorbidities (AOR [95% CI] 2.67 [1.36-5.24] p-value: 0.004). Overall, these results highlight the extensive SARS-CoV-2 Omicron circulation in children, mostly aged < 1 year, and provide insights on viral diversification even considering low-abundant SNPs, finally suggesting the potential contribution of viral diversification in affecting disease severity.

The Thousand Faces of Invasive Group A Streptococcal Infections: Update on Epidemiology, Symptoms, and Therapy.

Invasive infections caused by Streptococcus pyogfenes (iGAS), commonly known as Group A Streptococcus, represent a significant public health concern due to their potential for rapid progression and life-threatening complications. Epidemiologically, invasive GAS infections exhibit a diverse global distribution, affecting individuals of all ages with varying predisposing factors. The pathogenesis of invasive GAS involves an array of virulence factors that contribute to tissue invasion, immune evasion, and systemic dissemination. In pediatrics, in the last few years, an increase in iGAS infections has been reported worldwide becoming a challenging disease to diagnose and treat promptly. This review highlights the current knowledge on pathogenesis, clinical presentations, and therapeutic approaches for iGAS in children.

Use of Remdesivir in children with COVID-19: report of an Italian multicenter study.

BACKGROUND: COVID-19 is generally milder in children than in adults, however severe infection has been described in some patients. Few data are available on use of Remdesivir (RDV) in children, as most clinical trials focused on adult patients. We report a multicenter study conducted in 10 Italian Hospitals to investigate the safety of RDV in children affected by COVID-19. METHODS: We collected the clinical data of children with COVID-19 treated with RDV between March 2020 and February 2022 in 10 Italian hospitals. Clinical data were compared according to a duration of RDV therapy more or less than 5 days. Linear regression model was used to determine the association of significant variables from the bivariate analysis to the duration of RDV therapy. RESULTS: A total of 50 patients were included, with a median age of 12.8 years. Many patients had at least one comorbidity (78%), mostly obesity. Symptoms were fever (88%), cough (74%) and dyspnea (68%). Most patients were diagnosed with pneumonia of either viral and/or bacterial etiology. Blood test showed leukopenia in 66% and increased C-reactive protein (CRP) levels in 63% of cases. Thirty-six patients received RDV for 5 days, nine patients up to 10 days. Most children who received RDV longer were admitted to the PICU (67%). Treatment with RDV was well tolerated with rare side effects: bradycardia was recorded in 6% of cases, solved in less than 24 h after discontinuation. A mild elevation of transaminases was observed in 26% of cases, however for the 8%, it was still detected before the RDV administration. Therefore, in these cases, we could not establish if it was caused by COVID-19, RDV o both. Patients who received RDV for more than 5 days waited longer for its administration after pneumonia diagnosis. The presence of comorbidities and the duration of O2 administration significantly correlated with the duration of RDV therapy at the linear regression analysis. CONCLUSION: Our experience indicates that RDV against SARS-CoV-2 is safe and well-tolerated in pediatric populations at high risk of developing severe COVID-19. Our data suggest that delaying RDV therapy after diagnosis of pneumonia may be associated with a longer duration of antiviral therapy, especially in patients with comorbidities.

Antifungal Drug Usage in European Neonatal Units: A Multicenter Weekly Point Prevalence Study.

BACKGROUND: Data on antifungal prescribing in neonatal patients are limited to either single-center or single-country studies or to 1-day recording. Therefore, we assessed antifungal longitudinal usage in neonatal units (NUs) within Europe. METHODS: CALYPSO, a prospective weekly point prevalence study on antifungal drug usage in NUs in 18 hospitals (8 European countries), was conducted in 2020 during a 12-week period. All patients receiving systemic antifungals were included. Ward demographics were collected at the beginning; ward and patient data including indication, risk factors and antifungal regimen were weekly collected prospectively. RESULTS: Among 27 participating NUs, 15 (56%) practiced antifungal prophylaxis for neonates with birth weight <1000 g or <1500 g and additional risk factors. In total, 174 patients received antifungals with a median frequency per week of 10.5% ranging from 6.9% to 12.6%. Indication for antifungal prescribing was prophylaxis in 135/174 (78%) courses and treatment in 22% [39 courses (69% empirical, 10% preemptive, 21% targeted)]. Fluconazole was the most frequent systemic agent used both for prophylaxis (133/135) and treatment (15/39, 39%). Among neonates receiving prophylaxis, the most common risk factors were prematurity (119/135, 88%), mechanical ventilation (109/135, 81%) and central vascular catheters (89/135, 66%). However, gestational age <28 weeks was only recorded in 55/135 (41%) courses and birth weight <1000 g in 48/135 (35%). Most common reason for empirical treatment was late-onset sepsis; all 8 targeted courses were prescribed for invasive candidiasis. CONCLUSION: Antifungal usage in European NUs is driven by prophylaxis and empirical treatment with fluconazole being the most prescribed agent for both indications.

Plasma Protein Biomarkers Distinguish Multisystem Inflammatory Syndrome in Children From Other Pediatric Infectious and Inflammatory Diseases.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2. The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki disease or severe bacterial and viral infections, is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases. METHODS: Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n = 22), Kawasaki disease (n = 23), definite bacterial (n = 28) and viral (n = 27) disease and healthy controls (n = 8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C and association with severity of illness. RESULTS: Plasma levels of CD163, CXCL9 and PCSK9 were significantly elevated in MIS-C with a combined area under the receiver operating characteristic curve of 85.7% (95% confidence interval: 76.6%-94.8%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring inotropes, pediatric intensive care unit admission or with shock. CONCLUSION: Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.

Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.

Novel Beta Lactam Antibiotics for the Treatment of Multidrug-Resistant Gram-Negative Infections in Children: A Narrative Review.

Infections due to carbapenem-resistant Enterobacterales (CRE) are increasingly prevalent in children and are associated with poor clinical outcomes, especially in critically ill patients. Novel beta lactam antibiotics, including ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol, have been released in recent years to face the emerging challenge of multidrug-resistant (MDR) Gram-negative bacteria. Nonetheless, several novel agents lack pediatric indications approved by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA), leading to uncertain pediatric-specific treatment strategies and uncertain dosing regimens in the pediatric population. In this narrative review we have summarized the available clinical and pharmacological data, current limitations and future prospects of novel beta lactam antibiotics in the pediatric population.

The Prevalence of Carbapenemase-Producing Microorganisms and Use of Novel Cephalosporins for the Treatment of Severe Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria in a Pediatric Cardiac Intensive Care Unit.

BACKGROUND: The spread of carbapenem-resistant organisms (CROs) is an increasingly serious threat globally, especially in vulnerable populations, such as intensive care unit (ICU) patients. Currently, the antibiotic options for CROs are very limited, particularly in pediatric settings. We describe a cohort of pediatric patients affected by CRO infections, highlighting the important changes in carbapenemase production in recent years and comparing the treatment with novel cephalosporins (N-CEFs) to Colistin-based regimens (COLI). METHODS: All patients admitted to the cardiac ICU of the Bambino Gesù Children's Hospital in Rome during the 2016-2022 period with an invasive infection caused by a CRO were enrolled. RESULTS: The data were collected from 42 patients. The most frequently detected pathogens were Pseudomonas aeruginosa (64%), Klebsiella pneumoniae (14%) and Enterobacter spp. (14%). Thirty-three percent of the isolated microorganisms were carbapenemase producers, with a majority of VIM (71%), followed by KPC (22%) and OXA-48 (7%). A total of 67% of patients in the N-CEF group and 29% of patients in the comparative group achieved clinical remission (p = 0.04). CONCLUSION: The increase over the years of MBL-producing pathogens in our hospital is challenging in terms of therapeutic options. According to the present study, N-CEFs are a safe and effective option in pediatric patients affected by CRO infections.

Pediatric COVID-TB: A Clinical Perspective Based on the Analysis of Three Cases.

Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are currently two major causes of death among infectious diseases. Active tuberculosis and a history of tuberculosis appear to be associated with an increased risk of COVID-19. This coinfection, named COVID-TB, was never described in previously healthy children. We report three cases of pediatric COVID-TB. We describe three girls affected by tuberculosis, who tested positive for SARS-CoV-2. The first patient is a 5-year-old girl who was hospitalized for recurrent TB lymphadenopathy. As she never had any complications related to the concomitant infection with SARS-CoV-2, she received TB treatment. The second case is a 13-year-old patient with a history of pulmonary and splenic tuberculosis. She was admitted to the hospital due to deteriorating respiratory dynamics. She was already undergoing treatment for TB, but in the absence of improvement, she also required treatment for COVID-19. Slowly, the general condition improved until discharge. The last patient, a 10-year-old girl, was hospitalized for supraclavicular swelling. The investigations showed disseminated TB characterized by lung and bone involvement without COVID-19-related complications. She was treated with antitubercular and supportive therapy. Based on the data obtained from the adult population and our small experience, a pediatric patient with COVID-TB infection should be considered potentially at risk of worse clinical outcomes; for this reason, we suggest close observation, careful clinical management, and consideration of targeted anti-SARS-CoV-2 therapies.

The Use of Cefiderocol as Salvage Therapy in an Infant Receiving ECMO and Continuous Renal Replacement Therapy.

BACKGROUND: Infections caused by antimicrobial-resistant (AMR) pathogens are increasing worldwide, representing a serious global public health issue with high morbidity and mortality rates The treatment of Pseudomonas aeruginosa (PA) infections has become a significant challenge due to its ability to develop resistance to many of the currently available antibiotics, especially in intensive care unit (ICU) settings. Among the very few therapeutic lines available against extensively drug-resistant (XDR)-PA and/or with difficult-to-treat resistance (DTR)-PA, cefiderocol is an injectable siderophore cephalosporin not licensed for use in pediatric patients. There are only a few case reports and two ongoing trials describing the administration of this cephalosporin in infants. CASE PRESENTATION: This report describes the case of a critically ill 8-month-old girl affected by ventilator-associated pneumonia (VAP) infection complicated by bloodstream infection (BSI) sustained by VIM-producing PA. She was treated with cefiderocol as a salvage therapy during ECMO and CRRT support. CONCLUSIONS: In healthcare settings, treating multidrug-resistant, Gram-negative bacteria poses a serious challenge, especially in pediatric patients. Our findings suggest that cefiderocol can be considered as an off-label rescue therapy in selected pediatric cases.

The metaproteome of the gut microbiota in pediatric patients affected by COVID-19.

Introduction: The gut microbiota (GM) play a significant role in the infectivity and severity of COVID-19 infection. However, the available literature primarily focuses on adult patients and it is known that the microbiota undergoes changes throughout the lifespan, with significant alterations occurring during infancy and subsequently stabilizing during adulthood. Moreover, children have exhibited milder symptoms of COVID-19 disease, which has been associated with the abundance of certain protective bacteria. Here, we examine the metaproteome of pediatric patients to uncover the biological mechanisms that underlie this protective effect of the GM. Methods: We performed nanoliquid chromatography coupled with tandem mass spectrometry on a high resolution analytical platform, resulting in label free quantification of bacterial protein groups (PGs), along with functional annotations via COG and KEGG databases by MetaLab-MAG. Additionally, taxonomic assignment was possible through the use of the lowest common ancestor algorithm provided by Unipept software. Results: A COVID-19 GM functional dissimilarity respect to healthy subjects was identified by univariate analysis. The alteration in COVID-19 GM function is primarily based on bacterial pathways that predominantly involve metabolic processes, such as those related to tryptophan, butanoate, fatty acid, and bile acid biosynthesis, as well as antibiotic resistance and virulence. Discussion: These findings highlight the mechanisms by which the pediatric GM could contribute to protection against the more severe manifestations of the disease in children. Uncovering these mechanisms can, therefore, have important implications in the discovery of novel adjuvant therapies for severe COVID-19.

Severe viral respiratory infections in the pre-COVID era: A 5-year experience in two pediatric intensive care units in Italy.

BACKGROUND: Viral respiratory infections are one of the main causes of hospitalization in children. Even if mortality rate is low, 2% to 3% of the hospitalized children need mechanical ventilation. Risk factors for admission to the pediatric intensive care unit (PICU) are well known, while few studies have described risk factors for invasive ventilator support and prolonged hospitalization. METHODS: A retrospective study including all patients aged between 2 and 18 months with a confirmed viral respiratory infection, requiring admission to PICU from September to March between 2015 and 2019, was conducted at Bambino Gesù Children's Hospital in Rome, Italy. RESULTS: One hundred ninety patients were enrolled, with a median age of 2.7 months; 32.1% had at least one comorbidity, mainly prematurity. The most frequent isolated viruses were RSV-B, rhinovirus, and RSV-A; 38.4% needed mechanical ventilation. This subgroup of patients had lower median birth weight compared with patients not requiring mechanical ventilation (2800 g vs. 3180 g, p = 0.02); moreover, comorbidities were present in 43.8% of intubated patients and in 24.8% of patients treated with non-invasive ventilation (p = 0.006). Viral coinfection did not result to be a risk factor for mechanical support, while virus-bacteria coinfection was significantly associated with mechanical ventilation (p < 0.001). Similar risk factors were identified for prolonged hospitalization. CONCLUSIONS: Early identification of patients who could have a sudden respiratory deterioration and need of mechanical ventilation is crucial to reduce complications due to orotracheal intubation and prolonged hospitalization in PICU. Further studies are needed to define high-risk group of patients and to design targeted interventions.

Accuracy of Pancreatic Stone Protein for diagnosis of sepsis in children admitted to pediatric intensive care or high-dependency care: a pilot study.

BACKGROUND: Pancreatic Stone Protein (PSP) is one of the most promising diagnostic and prognostic markers. The aim of the study was to assess the accuracy of PSP, compared to C-Reactive Protein (CRP), and Procalcitonin (PCT) for sepsis diagnosis in pediatric patients. Furthermore, we explored the correlation of PSP levels with sepsis severity and organ failure measured with PELOD-2 score. METHODS: Forty pediatric patients were enrolled following admission to pediatric intensive care, high dependency care or pediatric ward. PSP blood levels were measured in Emergency Department (nanofluidic point-of-care immunoassay; abioSCOPE, Abionic SA, Switzerland) on day 1, 2, 3, 5 and 7 from the onset of the clinical signs and symptoms of sepsis or SIRS. Inclusion criteria were: 1) patient age (1 month to 18 years old), 2) signs and symptoms of SIRS, irrespective of association with organ dysfunction. Exclusion criteria were: 1) hemato-oncological diseases and/or immunodeficiencies, 2) pancreatic diseases. RESULTS: Septic patients showed higher PSP levels than those with non-infectious systemic inflammation. The optimal cut-off in diagnosis of sepsis for PSP at day 1 was 167 ng/ml resulted in a sensitivity of 59% (95% IC 36%-79%) and a specificity of 83% (95% IC 58%-96%) with an AUC of 0.636 for PSP in comparison to AUC of 0.722 for PCT and 0.503 for C-RP. ROC analysis for outcome (survival versus no survival) has showed AUC 0.814 for PSP; AUC 0.814 for PCT; AUC of 0.657 for C-RP. CONCLUSIONS: PSP could distinguish sepsis from non-infectious systemic inflammation; however, our results need to be confirmed in larger pediatric population.

The Relationship Between Pediatric Gut Microbiota and SARS-CoV-2 Infection.

This is the first study on gut microbiota (GM) in children affected by coronavirus disease 2019 (COVID-19). Stool samples from 88 patients with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 95 healthy subjects were collected (admission: 3-7 days, discharge) to study GM profile by 16S rRNA gene sequencing and relationship to disease severity. The study group was divided in COVID-19 (68), Non-COVID-19 (16), and MIS-C (multisystem inflammatory syndrome in children) (4). Correlations among GM ecology, predicted functions, multiple machine learning (ML) models, and inflammatory response were provided for COVID-19 and Non-COVID-19 cohorts. The GM of COVID-19 cohort resulted as dysbiotic, with the lowest α-diversity compared with Non-COVID-19 and CTRLs and by a specific ß-diversity. Its profile appeared enriched in Faecalibacterium, Fusobacterium, and Neisseria and reduced in Bifidobacterium, Blautia, Ruminococcus, Collinsella, Coprococcus, Eggerthella, and Akkermansia, compared with CTRLs (p < 0.05). All GM paired-comparisons disclosed comparable results through all time points. The comparison between COVID-19 and Non-COVID-19 cohorts highlighted a reduction of Abiotrophia in the COVID-19 cohort (p < 0.05). The GM of MIS-C cohort was characterized by an increase of Veillonella, Clostridium, Dialister, Ruminococcus, and Streptococcus and a decrease of Bifidobacterium, Blautia, Granulicatella, and Prevotella, compared with CTRLs. Stratifying for disease severity, the GM associated to "moderate" COVID-19 was characterized by lower α-diversity compared with "mild" and "asymptomatic" and by a GM profile deprived in Neisseria, Lachnospira, Streptococcus, and Prevotella and enriched in Dialister, Acidaminococcus, Oscillospora, Ruminococcus, Clostridium, Alistipes, and Bacteroides. The ML models identified Staphylococcus, Anaerostipes, Faecalibacterium, Dorea, Dialister, Streptococcus, Roseburia, Haemophilus, Granulicatella, Gemmiger, Lachnospira, Corynebacterium, Prevotella, Bilophila, Phascolarctobacterium, Oscillospira, and Veillonella as microbial markers of COVID-19. The KEGG ortholog (KO)-based prediction of GM functional profile highlighted 28 and 39 KO-associated pathways to COVID-19 and CTRLs, respectively. Finally, Bacteroides and Sutterella correlated with proinflammatory cytokines regardless disease severity. Unlike adult GM profiles, Faecalibacterium was a specific marker of pediatric COVID-19 GM. The durable modification of patients' GM profile suggested a prompt GM quenching response to SARS-CoV-2 infection since the first symptoms. Faecalibacterium and reduced fatty acid and amino acid degradation were proposed as specific COVID-19 disease traits, possibly associated to restrained severity of SARS-CoV-2-infected children. Altogether, this evidence provides a characterization of the pediatric COVID-19-related GM.