Preterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from 32 preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding microbial signatures of disease, we found that both the preterm infant microbiome and the metabolome were personalized and that the preterm infant gut microbiome is enriched in microbes that commonly dominate in the presence of antibiotics. These results contribute to the growing knowledge of the preterm infant microbiome and emphasize that a personalized view will be important to disentangle the health consequences of the preterm infant microbiome.

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rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site.

12Background: The assembly of the intestinal microbiota of extremely low birthweight (ELBW) infants has 13 an important impact on both immediate and long term health. ELBW infants are frequently given 14 antibiotics which are likely to perturb the assembly of the microbiota. Health complications are not 15 uncommon for ELBW infants; they face health crises including sepsis and necrotizing enterocolitis (NEC). 16Microbes are thought to be involved in the pathogenesis of NEC, but the mechanisms are unclear. New 17 understanding of the importance of human milk oligosaccharides and the establishment of a 18Bifidobacteria-dominated gut microbiota early in infancy suggest that all preterm infants have abnormal 19 microbial colonization. The initial assembly of intestinal microbial communities may have significant 20 impact on immune development and lifelong health. 21Results: We measured the bacterial composition and metabolite profile of 32 ELBW infants by 16S rRNA 22 gene sequencing and untargeted gas chromatography mass spectrometry of fecal samples. Infants 23 either remained healthy, developed late-onset sepsis, or developed necrotizing enterocolitis. The 24 . CC-BY-NC 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/125922 doi: bioRxiv preprint first posted online Apr. 10, 2017; 2 bacterial compositions were similar to what has been observed in other studies of preterm infants. Fecal 25 samples are dominated by aero-tolerant bacterial species, specifically Enterococcus, Enterobacteriaceae, 26 and Staphylococcus. Only three ELBW infants were colonized by Bifidobacteria. Fecal samples from 27 infants who developed NEC were not distinguishable from other infant samples based on bacterial 28 compositions (Permanova R 2 < 0.001, p = 0.99) or metabolite profiles (Permanova R 2 = 0.05, p= 0.24). 29Instead the bacterial composition (R 2 = 0.63, p < 0.001) and metabolite profile (R 2 = 0.43, p < 0.001) were 30 highly personalized for each infant. There were not significant correlations between the bacterial 31 composition and metabolite profiles of fecal samples (Mantel test r= 0.18, p < 0.001). 32Conclusions: Although antibiotics likely contribute to the instability of the ELBW infant intestinal 33 microbiota, personalized signatures of bacteria and metabolites are still clearly present. Neither the 34 bacterial composition or metabolite profile was unique in cases of disease. While bacteria certainly 35 contribute to the profile of metabolites present in feces, in these ELBW infants, significant correlations 36 between bacterial relative abundances as determined by 16S rRNA gene sequencing and untargeted GC-37 MS metabolite profiles were not detectable. 38 39 Background 40The intestinal microbiota of infants initially assembles by exposure to the mother's microbiota as well as 41 exposure to microbes in the environment [1]. In the first few days, the intestines are colonized by 42...

Background Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management, but also in characterizing prognosis. Usual care testing by culture and PCR is often unable to identify a pathogen. We examined the systematic application of metagenomic next-generation sequencing (mNGS) for detecting organisms and transcriptomic analysis of cerebrospinal fluid (CSF) in children with CNS infections. Methods We conducted a prospective multi-site study that aimed to enroll all children with a CSF pleocytosis and suspected CNS infection admitted to one of three tertiary pediatric hospitals during the study timeframe. After usual care testing had been performed, the remaining CSF was sent for mNGS and transcriptomic analysis. Results We screened 221 and enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 25 (35.7%) subjects by any diagnostic modality. mNGS of the CSF samples identified a pathogen in 20 (28.6%) subjects, which were also all identified by usual care testing. The median time to result was 38 hours. Conclusion Metagenomic sequencing of CSF has the potential to rapidly identify pathogens in children with CNS infections.

Background: Therapies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its life-threatening respiratory infection coronavirus disease 2019 (COVID-19) have been evaluated, including COVID-19 convalescent plasma (CCP). Multiple large reports of CCP treatment in adults exist. Pediatric data on CCP safety and efficacy are limited. Methods: Single-center prospective, open-label trial looking at safety, antibody kinetics and outcomes of CCP (10 mL/kg, max 1 unit) treatment for COVID-19 in hospitalized pediatric patients with moderate to severe disease or at high-risk for serious illness. Results: Thirteen patients were enrolled. No infusion-related adverse events occurred. No hematologic or metabolic adverse events were noted during hospitalization or at 3-weeks. Ten patients had clinical improvement by day 7 (WHO eight-category ordinal severity scale for COVID-19). Following CCP, anti-SARS-CoV-2 anti-nucleocapsid IgG increased significantly at 24 hours and high levels were sustained at 7-and 21-days. Transient IgM response was noted. Twelve patients (92.3%) were discharged home, 9 (75%) by day 7 post-CCP. One remained on invasive ventilatory support 42 days after CCP and was eventually discharged to an intermediate care facility. The single patient death was retrospectively confirmed to have had brain death before CCP. Conclusion: CCP was well tolerated in pediatric patients, resulted in rapid antibody increase, and did not appear to interfere with immune responses measured at 21 days. More pediatric data are necessary to establish the efficacy of CCP, but our data suggest benefit in moderate to severe COVID-19 when used early. Other immunologic or antiviral interventions may be added as supported by emerging data.

Background and Objectives: Convalescent COVID-19 plasma (CCP) was developed and used worldwide as a treatment option by supplying passive immunity. Adult studies suggest administering high-titer CCP early in the disease course of patients who are expected to be antibody-negative; however, pediatric experience is limited. We created a multi-institutional registry to characterize pediatric patients (<18 years) who received CCP and to assess the safety of this intervention.Methods: A REDCap survey was distributed. The registry collected deidentified data including demographic information (age, gender, and underlying conditions), COVID-19 disease features and concurrent treatments, CCP transfusion and safety events, and therapy response.Abbreviations: CCP, COVID-19 convalescent plasma; CTCAE, common terminology criteria for adverse events; EBV, estimated blood volume; FDA, United States Food and Drug Administration; MIS-C, multisystem inflammatory syndrome in children; REDCap, research electronic data capture.

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