Presentations and Outcomes Among Infants ≤90 Days With and Without SARS-CoV-2.

OBJECTIVES: To compare symptoms and outcomes among infants aged ≤90 days tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a broad, international sample of emergency departments (EDs). METHODS: This was a secondary analysis of infants aged 0 to 90 days with suspected SARS-CoV-2 infections tested using molecular approaches and with 14-day follow-up. The parent studies were conducted at 41 EDs in 10 countries (the global Pediatric Emergency Research Network; March 2020-June 2021) and 14 EDs across Canada (Pediatric Emergency Research Canada network; August 2020-February 2022). Symptom profiles included presence and number of presenting symptoms. Clinical outcomes included hospitalization, ICU admission, and severe outcomes (a composite of intensive interventions, severe organ impairment, or death). RESULTS: Among 1048 infants tested for SARS-CoV-2, 1007 (96.1%) were symptomatic at presentation and 432 (41.2%) were SARS-CoV-2-positive. A systemic symptom (any of the following: Apnea, drowsiness, irritability, or lethargy) was most common and present in 646 (61.6%) infants, regardless of SARS-CoV-2 status. Although fever and upper respiratory symptoms were more common among SARS-CoV-2-positive infants, dehydration, gastrointestinal, skin, and oral symptoms, and the overall number of presenting symptoms did not differ between groups. Infants with SARS-CoV-2 infections were less likely to be hospitalized (32.9% vs 44.8%; difference -11.9% [95% confidence interval (CI) -17.9% to -6.0%]), require intensive care (1.4% vs 5.0%; difference -3.6% [95% CI -5.7% to -1.6%]), and experience severe outcomes (1.4% vs 5.4%; difference -4.0% [95% CI -6.1% to -1.9%]). CONCLUSIONS: SARS-CoV-2 infections may be difficult to differentiate from similar illnesses among the youngest infants but are generally milder. SARS-CoV-2 testing can help inform clinical management.

Post-COVID-19 Condition in Children 6 and 12 Months After Infection.

Importance: There is a need to understand the long-term outcomes among children infected with SARS-CoV-2. Objective: To quantify the prevalence of post-COVID-19 condition (PCC) among children tested for SARS-CoV-2 infection in pediatric emergency departments (EDs). Design, Setting, and Participants: Multicenter, prospective cohort study at 14 Canadian tertiary pediatric EDs that are members of the Pediatric Emergency Research Canada network with 90-day, 6-month, and 12-month follow-up. Participants were children younger than 18 years who were tested for SARS-CoV-2 infection between August 2020 and February 2022. Data were analyzed from May to November 2023. Exposure: The presence of SARS-CoV-2 infection at or within 14 days of the index ED visit. Main Outcomes and Measures: Presence of symptoms and QoL reductions that meet the PCC definition. This includes any symptom with onset within 3 months of infection that is ongoing at the time of follow-up and affects everyday functioning. The outcome was quantified at 6 and 12 months following the index ED visit. Results: Among the 5147 children at 6 months (1152 with SARS-CoV-2 positive tests and 3995 with negative tests) and 5563 children at 12 months (1192 with SARS-CoV-2 positive tests and 4371 with negative tests) who had sufficient data regarding the primary outcome to enable PCC classification, the median (IQR) age was 2.0 (0.9-5.0) years, and 2956 of 5563 (53.1%) were male. At 6-month follow-up, symptoms and QoL changes consistent with the PCC definition were present in 6 of 1152 children with positive SARS-CoV-2 tests (0.52%) and 4 of 3995 children with negative SARS-CoV-2 tests (0.10%; absolute risk difference, 0.42%; 95% CI, 0.02% to 0.94%). The PCC definition was met at 12 months by 8 of 1192 children with positive SARS-CoV-2 tests (0.67%) and 7 of 4371 children with negative SARS-CoV-2 tests (0.16%; absolute risk difference, 0.51%; 95% CI, 0.06 to 1.08%). At 12 months, the median (IQR) PedsQL Generic Core Scale scores were 98.4 (90.0-100) among children with positive SARS-CoV-2 tests and 98.8 (91.7-100) among children with negative SARS-CoV-2 tests (difference, -0.3; 95% CI, -1.5 to 0.8; P = .56). Among the 8 children with SARS-CoV-2 positive tests and PCC at 12-month follow-up, children reported respiratory (7 of 8 patients [88%]), systemic (3 of 8 patients [38%]), and neurologic (1 of 8 patients [13%]) symptoms. Conclusions and Relevance: In this cohort study of children tested for SARS-CoV-2 infection in Canadian pediatric EDs, although children infected with SARS-CoV-2 reported increased chronic symptoms, few of these children developed PCC, and overall QoL did not differ from children with negative SARS-CoV-2 tests.

Biocompatibility and antibacterial activity of MgO/Ca3(PO4)2 composite ceramic scaffold based on vat photopolymerization technology.

Recent advancements in medical technology and increased interdisciplinary research have facilitated the development of the field of medical engineering. Specifically, in bone repair, researchers and potential users have placed greater demands on orthopedic implants regarding their biocompatibility, degradation rates, antibacterial properties, and other aspects. In response, our team developed composite ceramic samples using degradable materials calcium phosphate and magnesium oxide through the vat photopolymerization (VP) technique. The calcium phosphate content in each sample was, respectively, 80 %, 60 %, 40 %, and 20 %. To explore the relationship between the biocompatibility, antibacterial activity, and MgO content of the samples, we cultured them with osteoblasts (MC3T3-E1), Escherichia coli (a gram-negative bacterium), and Staphylococcus aureus (a gram-positive bacterium). Our results demonstrate that as the MgO content of the sample increases, its biocompatibility improves but its antibacterial activity decreases. Regarding the composite material samples, the 20 % calcium phosphate content group exhibited the best biocompatibility. However, after 0.5 h of co-cultivation, the antibacterial rates of all groups except the 20 % calcium phosphate content group co-cultured with S. aureus exceed 80 %. Furthermore, after 3 h, the antibacterial rates against E. coli exceed 95 % in all groups. This is because higher levels of MgO correspond to lower pH values and Mg2+ concentrations in the cell and bacterial culture solutions, which ultimately promote cell and bacterial proliferation. This elevates the biocompatibility of the samples, albeit at the expense of their antimicrobial efficacy. Thus, modulating the MgO content in the composite ceramic samples provides a strategy to develop gradient composite scaffolds for better control of their biocompatibility and antibacterial performance during different stages of bone regeneration.

Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children.

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 109/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 109/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.

Molecular epidemiology of rotavirus among children in Western Canada: Dynamic changes in genotype prevalence in four consecutive seasons.

Rotavirus molecular surveillance remains important in the postvaccine era to monitor the changes in transmission patterns, identify vaccine-induced antigenic changes and discover potentially pathogenic vaccine-related strains. The Canadian province of Alberta introduced rotavirus vaccination into its provincial vaccination schedule in June 2015. To evaluate the impact of this program on stool rotavirus positivity rate, strain diversity, and seasonal trends, we analyzed a prospective cohort of children with acute gastroenteritis recruited between December 2014 and August 2018. We identified dynamic changes in rotavirus positivity and genotype trends during pre- and post-rotavirus vaccine introduction periods. Genotypes G9P[8], G1P[8], G2P[4], and G12P[8] predominated consecutively each season with overall lower rotavirus incidence rates in 2016 and 2017. The demographic and clinical features of rotavirus gastroenteritis were comparable among wild-type rotaviruses; however, children with G12P[8] infections were older (p < 0.001). Continued efforts to monitor changes in the molecular epidemiology of rotavirus using whole genome sequence characterization are needed to further understand the impact of the selection pressure of vaccination on rotavirus evolution.

Significantly Longer Shedding of Norovirus Compared to Rotavirus and Adenovirus in Children with Acute Gastroenteritis.

Worldwide, acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children under 5 years of age. Viruses, including norovirus, rotavirus, and enteric adenovirus, are the leading causes of pediatric AGE. In this prospective cohort study, we investigated the viral load and duration of shedding of norovirus, rotavirus, and adenovirus in stool samples collected from 173 children (median age: 15 months) with AGE who presented to emergency departments (EDs) across Canada on Day 0 (day of enrollment), and 5 and 28 days after enrollment. Quantitative RT-qPCR was performed to assess the viral load. On Day 0, norovirus viral load was significantly lower compared to that of rotavirus and adenovirus (p < 0.001). However, on Days 5 and 28, the viral load of norovirus was higher than that of adenovirus and rotavirus (p < 0.05). On Day 28, norovirus was detected in 70% (35/50) of children who submitted stool specimens, while rotavirus and adenovirus were detected in 52.4% (11/24) and 13.6% (3/22) of children (p < 0.001), respectively. Overall, in stool samples of children with AGE who presented to EDs, rotavirus and adenovirus had higher viral loads at presentation compared to norovirus; however, norovirus was shed in stool for the longest duration.

Liver transaminase concentrations in children with acute SARS-CoV-2 infection.

OBJECTIVE: To evaluate the relationship between SARS-CoV-2 infection and liver injury by comparing transaminase concentrations among children tested for SARS-CoV-2 and other respiratory viruses in pediatric emergency departments. DESIGN & METHODS: Eligible children were <18 years with suspected SARS-CoV-2, tested using molecular approaches in emergency departments between March 7, 2020, and June 15, 2021 (Pediatric Emergency Research Network), and between August 6, 2020, and February 22, 2022 (Pediatric Emergency Research Canada). We compared aspartate (AST) and alanine aminotransferase (ALT) concentrations at presentation for SARS-CoV-2 and other respiratory viruses through a multivariate linear regression model, with the natural log of serum transaminase concentrations as dependent variables. RESULTS: Of 16,892 enrolled children, 2,462 (14.6%) had transaminase concentrations measured; 4318 (25.6%) were SARS-CoV-2 positive, and 3932 (23.3%) were tested for additional respiratory viruses. Among study participants who had additional respiratory virus testing performed, the most frequently identified viruses were enterovirus/rhinovirus [8.7% (343/3,932)], respiratory syncytial virus [4.6% (181/3,932)], and adenovirus [2.6% (103/3,932)]. Transaminase concentrations were elevated in 25.6% (54/211) of children with isolated SARS-CoV-2 detection and 21.6% (117/541) of those with no virus isolated; P = 0.25. In the multivariable model, isolated SARS-CoV-2 detection was not associated with elevated ALT (adjusted geometric mean ratio (IU/L): 0.96; 95%Confidence Interval (CI): 0.84, 1.08) or AST (adjusted geometric mean ratio (IU/L): 1.03; 95%CI: 0.92, 1.16) concentrations, with negative respiratory panel as the referent group. Ninety-day follow-up was completed in 82.2% (3,550/4,318) of SARS-CoV-2 positive children; no cases of new-onset liver disease were reported. CONCLUSION: Among those tested, transaminase concentrations did not vary between SARS-CoV-2-positive children and those with a negative respiratory viral panel. In multivariate analysis, SARS-CoV-2 infection was not associated with increased initial transaminase concentrations compared to other respiratory viruses.

Visits to Alberta Emergency Departments for Child Mental Health Concerns During the COVID-19 Pandemic: An Examination of Visit Trends in Relation to School Closures and Reopenings.

OBJECTIVE: We examined emergency department (ED) mental health visit trends by children in relation to periods of school closure and reopening during the COVID-19 pandemic in Alberta, Canada. METHODS: Mental health visits by school-aged children (5 to <18 years) were extracted from the Emergency Department Information System, a province-wide database, from March 11, 2020, to November 30, 2021 (pandemic period; n = 18,997) and March 1, 2019, to March 10, 2020 (1-year, prepandemic comparator period; n = 11,540). We calculated age-specific visit rates and compared rate differences between periods of school closure (March 15-June 30, 2020; November 30, 2020-January 10, 2021; April 22-June 30, 2021) and reopening (September 4-November 29, 2020; January 11-April 21, 2021; September 3-November 30, 2021) to matched prepandemic periods. We used a ratio of relative risk to examine the risk of a visit during closures versus reopenings. RESULTS: The cohort included 11,540 prepandemic visits and 18,997 pandemic visits. Compared with prepandemic periods, ED visit rates increased across all ages during the first (+85.53%; 95% confidence interval [CI], 73.68% to 100.41%) and third (+19.92%; 95% CI, 13.28% to 26.95%) school closures, and decreased during the second closure (-15.37%; 95% CI, -22.22% to -7.92%). During school reopenings, visit rates decreased across all ages during the first reopening (-9.30%; 95% CI, -13.94% to -4.41%) and increased during the third reopening (+13.59%; 95% CI, 8.13% to 19.34%); rates did not change significantly during the second reopening (2.54%; 95% CI, -3.45% to 8.90%). The risk of a visit during school closure versus reopening was only higher for the first closure with 2.06 times the risk (95% CI, 1.88 to 2.25). CONCLUSIONS: Emergency department mental health visit rates were highest during the first school closure of the COVID-19 pandemic, and the risk of a visit during this closure period was twice compared with when schools first reopened.

Comparison of a Rapid Multiplex Gastrointestinal Panel with Standard Laboratory Testing in the Management of Children with Hematochezia in a Pediatric Emergency Department: Randomized Controlled Trial.

Advances in diagnostic microbiology allow for the rapid identification of a broad range of enteropathogens; such knowledge can inform care and reduce testing. We conducted a randomized, unblinded trial in a tertiary-care pediatric emergency department. Participants had stool (and rectal swabs if stool was not immediately available) tested using routine microbiologic approaches or by use of a device (BioFire FilmArray gastrointestinal panel), which identifies 22 pathogens with a 1-h instrument turnaround time. Participants were 6 months to <18.0 years and had acute bloody diarrhea. Primary outcome was performance of blood tests within 72 h. From 15 June 2018 through 7 May 2022, 60 children were randomized. Patients in the BioFire FilmArray arm had a reduced time to test result (median 3.0 h with interquartile range [IQR] of 3.0 to 4.0 h, versus 42.0 h (IQR 23.5 to 47.3 h); difference of -38.0 h, 95% confidence interval [CI] of -41.0 to -22.0 h). Sixty-five percent (20/31) of participants in the BioFire FilmArray group had a pathogen detected-most frequently enteropathogenic Escherichia coli (19%), Campylobacter (16%), and Salmonella (13%). Blood tests were performed in 52% of children in the BioFire FilmArray group and 62% in the standard-of-care group (difference of -10.5%, 95% CI of -35.4% to 14.5%). There were no between-group differences in the proportions of children administered intravenous fluids, antibiotics, hospitalized, or who had diagnostic imaging performed. Testing with the BioFire FilmArray reduced the time to result availability by 38 h. Although statistical significance was limited by study power, BioFire FilmArray use was not associated with clinically meaningful reductions in health care utilization or improved outcomes. IMPORTANCE Advances in diagnostic microbiology now allow for the faster and more accurate detection of an increasing number of pathogens. We determined, however, that in children with acute bloody diarrhea, these advances did not necessarily translate into improved clinical outcomes. While a greater number of pathogens was identified using a rapid turnaround multiplex stool diagnostic panel, with a reduction in the time to stool test result of over 1.5 days, this did not alter the practice of pediatric emergency medicine physicians, who continued to perform blood tests on a large proportion of children. While our conclusions may be limited by the relatively small sample size, targeted approaches that educate clinicians on the implementation of such technology into clinical care will be needed to optimize usage and maximize benefits.

Predictors of Adherence to Short-Course Probiotics Among Children with Gastroenteritis who are Enrolled in a Clinical Trial.

BACKGROUND: To improve our understanding of adherence to discharge medications in the ED and within research trials, we sought to quantify medication adherence and identify predictors thereof in children with acute gastroenteritis (AGE). METHODS: We conducted a secondary analysis of a randomized trial of twice daily probiotic for 5 days. The population included previously healthy children aged 3-47 months with AGE. The primary outcome was patient-reported adherence to the treatment regimen, defined a priori as having received >70% of the prescribed doses. Secondary outcomes included predictors of treatment adherence and concordance between patient-reported adherence and the returned medication sachet counts. RESULTS: After excluding participants with missing data on adherence, 760 participants were included in this analysis: 383 in the probiotic arm (50.4%); and 377 in the placebo arm (49.6%). Self-reported adherence was similar in both groups (77.0% in probiotic versus 80.3% in placebo). There was good agreement between self-reported adherence and sachet counts (87% within limits of agreement (-2.9 to 3.5 sachets) on the Bland-Altman plots). In the multivariable regression model, covariates associated with adherence were greater number of days of diarrhea post-emergency department visit, and the study site; covariates negatively associated with adherence were age 12-23 months, severe dehydration and greater total number of vomiting and diarrhea episodes after enrolment. CONCLUSIONS: Longer duration of diarrhea and study site were associated with higher probiotic adherence. Age 12-23 months, severe dehydration and greater number of vomiting and diarrhea episodes post enrolment negatively predicted treatment adherence.

Correction to "Using Imidazo[2,1-b][1,3,4]thiadiazol Skeleton to Design and Synthesize Novel MNK Inhibitors".

[This corrects the article DOI: 10.1021/acsmedchemlett.2c00442.].

Comparison of Symptoms Associated With SARS-CoV-2 Variants Among Children in Canada.

Importance: Clinical manifestations of SARS-CoV-2 variants have not been systematically compared in children. Objective: To compare symptoms, emergency department (ED) chest radiography, treatments, and outcomes among children with different SARS-CoV-2 variants. Design, Setting, and Participants: This multicenter cohort study was performed at 14 Canadian pediatric EDs. Participants included children and adolescents younger than 18 years (hereinafter referred to as children) tested for SARS-CoV-2 infection in an ED between August 4, 2020, and February 22, 2022, with 14 days of follow-up. Exposure(s): SARS-CoV-2 variants detected on a specimen collected from the nasopharynx, nares, or throat. Main Outcomes and Measures: The primary outcome was presence and number of presenting symptoms. The secondary outcomes were presence of core COVID-19 symptoms, chest radiography findings, treatments, and 14-day outcomes. Results: Among 7272 participants presenting to an ED, 1440 (19.8%) had test results positive for SARS-CoV-2 infection. Of these, 801 (55.6%) were boys, with a median age of 2.0 (IQR, 0.6-7.0) years. Children with the Alpha variant reported the fewest core COVID-19 symptoms (195 of 237 [82.3%]), which were most often reported by participants with Omicron variant infection (434 of 468 [92.7%]; difference, 10.5% [95% CI, 5.1%-15.9%]). In a multivariable model with the original type as the referent, the Omicron and Delta variants were associated with fever (odds ratios [ORs], 2.00 [95% CI, 1.43-2.80] and 1.93 [95% CI, 1.33-2.78], respectively) and cough (ORs, 1.42 [95% CI, 1.06-1.91] and 1.57 [95% CI, 1.13-2.17], respectively). Upper respiratory tract symptoms were associated with Delta infection (OR, 1.96 [95% CI, 1.38-2.79]); lower respiratory tract and systemic symptoms were associated with Omicron variant infection (ORs, 1.42 [95% CI, 1.04-1.92] and 1.77 [95% CI, 1.24-2.52], respectively). Children with Omicron infection most often had chest radiography performed and received treatments; compared with those who had Delta infection, they were more likely to have chest radiography performed (difference, 9.7% [95% CI, 4.7%-14.8%]), to receive intravenous fluids (difference, 5.6% [95% CI, 1.0%-10.2%]) and corticosteroids (difference, 7.9% [95% CI, 3.2%-12.7%]), and to have an ED revisit (difference, 8.8% [95% CI, 3.5%-14.1%]). The proportions of children admitted to the hospital and intensive care unit did not differ between variants. Conclusions and Relevance: The findings of this cohort study of SARS-CoV-2 variants suggest that the Omicron and Delta variants were more strongly associated with fever and cough than the original-type virus and the Alpha variant. Children with Omicron variant infection were more likely to report lower respiratory tract symptoms and systemic manifestations, undergo chest radiography, and receive interventions. No differences were found in undesirable outcomes (ie, hospitalization, intensive care unit admission) across variants.

Using Imidazo[2,1-b][1,3,4]thiadiazol Skeleton to Design and Synthesize Novel MNK Inhibitors.

Mitogen-activated protein kinase-interacting protein kinases (MNKs) phosphorylate eukaryotic initiation factor 4E (eIF4E) and regulate the processes of cell proliferation, cell cycle, and migration and invasion of cancer cells. Selectively inhibiting the activity of MNKs could be effective in treating cancers. In this study, we report a series of novel MNK inhibitors with an imidazo[2,1-b][1,3,4]thiadiazol scaffold, from which, compound 18 inhibited the phosphorylation of eIF4E in various cancer cell lines potently. Compound 18 was more potent against MNK2 than MNK1, and decreased the levels of cyclin-B1, cyclin-D3, and MMP-3 in A549 and MDA-MB-231 cells, impaired cell growth and colony formation, arrested the cell cycle in the G0/G1 phase, and inhibited cell migration and the secretion of TNF-α, MCP-1, and IL-8 from A549 cells. It represents a starting compound to design further inhibitors that selectively target MNKs and apply in other diseases.

Characterizing the Pain Experience of Children With Acute Gastroenteritis Based on Identified Pathogens.

OBJECTIVES: Pain is common with acute gastroenteritis (AGE) yet little is known about the severity associated with specific enteropathogens. We sought to explore the correlation of pain severity with specific enteropathogens in children with AGE. METHODS: Participants were prospectively recruited by the Alberta Provincial Pediatric EnTeric Infection TEam at 2 pediatric emergency departments (EDs) (December 2014-August 2018). Pain was measured (by child and/or caregiver) using the 11-point Verbal Numerical Rating Scale. RESULTS: We recruited 2686 participants; 46.8% (n = 1256) females, with median age 20.1 months (interquartile range 10.3, 45.3). The mean highest pain scores were 5.5 [standard deviation (SD) 3.0] and 4.2 (SD 2.9) in the 24 hours preceding the ED visit, and in the ED, respectively. Prior to ED visit, the mean highest pain scores with bacterial detection were 6.6 (SD 2.5), compared to 5.5 (SD 2.9) for single virus and 5.5 (SD 3.1) for negative stool tests. In the ED, the mean highest pain scores with bacterial detection were 5.5 (SD 2.7), compared to 4.1 (SD 2.9) for single virus and 4.2 (SD 3.0) for negative stool tests. Using multivariable modeling, factors associated with greater pain severity prior to ED visit included older age, fever, illness duration, number of diarrheal or vomiting episodes in the preceding 24 hours, and respiratory symptoms, but not enteropathogen type. CONCLUSION: Children with AGE experience significant pain, particularly when the episode is associated with the presence of a bacterial enteric pathogen. However, older age and fever appear to influence children's pain experiences more than etiologic pathogens.

Comparative Evaluation of Luminex xTAG® Gastrointestinal Pathogen Panel and Direct-From-Stool Real-Time PCR for Detection of C. difficile Toxin tcdB in Stool Samples from a Pediatric Population.

Detection of Clostridioides difficile toxins in patients with gastroenteritis has increasingly been accomplished through the use of enteric multiplex syndromic panels. Comparisons of the performance of these panels to both direct-from-stool (DFS) and culture-enriched stools followed by polymerase chain reaction (PCR) methods in pediatric populations are limited. Here, we compare the performance of the Luminex xTAG® Gastrointestinal Pathogen Panel (GPP) to our DFS in-house real-time PCR (DFS RT-PCR) assay for the detection of C. difficile toxin gene, tcdB, using 2641 stool specimens collected from children enrolled in the Alberta Provincial Pediatric EnTeric Infection Team (APPETITE) study in Alberta, Canada. We used culture enrichment followed by in-house RT-PCR to resolve discordant results between the two assays. We found excellent agreement (k = 0.89) between the GPP and our DFS RT-PCR assay: the positive percent agreement between the two assays was 97%, and the negative percent agreement was 99%. GPP, a multi-analyte platform can easily be implemented into a routine diagnostic laboratory for detecting enteric pathogens including C. difficile.

Intestinal Microbial Composition of Children in a Randomized Controlled Trial of Probiotics to Treat Acute Gastroenteritis.

Compositional analysis of the intestinal microbiome in pre-schoolers is understudied. Effects of probiotics on the gut microbiota were evaluated in children under 4-years-old presenting to an emergency department with acute gastroenteritis. Included were 70 study participants (n=32 placebo, n=38 probiotics) with stool specimens at baseline (day 0), day 5, and after a washout period (day 28). Microbiota composition and deduced functions were profiled using 16S ribosomal RNA sequencing and predictive metagenomics, respectively. Probiotics were detected at day 5 of administration but otherwise had no discernable effects, whereas detection of bacterial infection (P<0.001) and participant age (P<0.001) had the largest effects on microbiota composition, microbial diversity, and deduced bacterial functions. Participants under 1 year had lower bacterial diversity than older aged pre-schoolers; compositional changes of individual bacterial taxa were associated with maturation of the gut microbiota. Advances in age were associated with differences in gut microbiota composition and deduced microbial functions, which have the potential to impact health later in life. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01853124.

Post-COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection.

Importance: Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children. Objectives: To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs. Design, Setting, and Participants: This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls. Exposure: SARS-CoV-2 detected via nucleic acid testing. Main Outcomes and Measures: Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. Results: Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]). Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.

Corticosteroids and Other Treatments Administered to Children Tested for SARS-CoV-2 Infection in Emergency Departments.

OBJECTIVE: We sought to determine if corticosteroid administration is associated with a SARS-CoV-2 nucleic acid test-positive result and to describe therapies administered to SARS-CoV-2 infected children. METHODS: We collected cross-sectional data from participants recruited in 41 pediatric emergency departments (ED) in 10 countries between March 2020 and June 2021. Participants were <18 years old, had signs or symptoms of, or risk factors for acute SARS-CoV-2 infection, and had nucleic acid testing performed. To determine if SARS-CoV-2 test status was independently associated with corticosteroid administration, we used a multivariable conditional logistic regression model matched by study site to compare treatments administered based on SARS-CoV-2 test and disposition status. This analysis was repeated for the subgroup of study participants who were hospitalized. RESULTS: 30.3% (3,121/10,315) of participants were SARS-CoV-2-positive. Although remdesivir was more commonly administered to SARS-CoV-2-positive children, use was infrequent (25/3120 [0.8%] vs 1/7188 [0.01%]; P = .001). Corticosteroid use was less common among SARS-CoV-2-positive children (219/3120 [7.0%] vs 759/7190 [10.6%]; P < .001). Among hospitalized children, there were no differences in provision of inotropes, respiratory support, chest drainage or extracorporeal membrane oxygenation between groups. Corticosteroid administration was associated with age, history of asthma, wheezing, study month, hospitalization and intensive care unit admission; it was not associated with a positive SARS-CoV-2 test result overall (aOR: 0.91; 95%CI: 0.74, 1.12) or among the subgroup of those hospitalized (aOR: 1.04; 95%CI: 0.75, 1.44). CONCLUSIONS: Few disease-specific treatments are provided to SARS-CoV-2-positive children; clinical trials evaluating therapies in children are urgently needed.