Molecular Point-of-Care Testing in the Emergency Department for Group A Streptococcus Pharyngitis: A Randomized Trial.

OBJECTIVES: To compare clinical and health systems outcomes of rapid molecular testing versus throat culture recovery for the management of group A Streptococcus (GAS) pharyngitis in a pediatric emergency department (PED). METHODS: We conducted a single-center randomized trial of children (3-17 years) presenting to a PED with suspected GAS pharyngitis. A single dual-headed throat swab was collected, and participants were randomized to 1 of 2 parallel treatment groups with 1:1 allocation: point-of-care (POC) nucleic acid amplification testing or standard throat culture. The primary outcomes were time to throat pain +/- fever resolution. Secondary outcomes included absenteeism, length of stay, return visits to care, and antibiotic prescriptions and utilization. RESULTS: A total of 227 children were randomly assigned to culture (n = 115) or POC (n = 112) testing. Antibiotics were initiated earlier in the POC group by approximately 1 day (95% confidence interval, -0.40 to -1.58). No associated difference in time to throat pain or fever resolution was observed between groups. There was a decrease in the proportion of prescribed antibiotics in the POC group (0.35) compared with the culture group (0.79; P < 0.001). Otherwise, no significant differences in secondary outcomes were observed. CONCLUSIONS: Establishing a POC nucleic acid amplification testing program for GAS in a PED facilitates earlier treatment and fewer antibiotic prescriptions. Although this did not translate to improved clinical and health systems outcomes in our study, it may serve as an important tool amid evolving pediatric febrile illnesses and growing antimicrobial resistance patterns.

A Novel Anti-nucleocapsid Antibody Avidity Method for Identifying SARS-CoV-2 Reinfections.

Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections is challenging with current serology assays and is further complicated by the marked decrease in routine viral testing practices as viral transmission increased during Omicron. Here, we provide proof-of-principle that high-avidity anti-nucleocapsid (N) antibodies detects reinfections after a single infection with higher specificity (85%; 95% confidence interval [95% CI], 80%-90%) compared to anti-N antibody levels (72%; 95% CI, 66%-79%) in a vaccinated cohort. This method could be used to retroactively investigate the epidemiology and incremental long-term health consequences of SARS-CoV-2 reinfections.

Investigating the Antibody Imprinting Hypothesis among Canadian Paramedics after SARS-CoV-2 Omicron Variant Circulation.

Recent research has highlighted the Omicron variant's capacity to evade immune protection conferred by wild-type (WT) mRNA vaccines. Despite this observation, the potential involvement of antigenic sin phenomena remains unclear. Our hypothesis posited that a greater number of prior WT vaccine doses might lead to reduced anti-Omicron neutralization Abs following Omicron infection. To investigate this, we analyzed blood samples from human participants in the COVID-19 Occupational Risk, Seroprevalence, and Immunity among Paramedics (CORSIP) study who had received at least one WT mRNA vaccine before contracting Omicron. The exposure variable was the number of WT mRNA vaccines administered, and the outcome was the angiotensin-converting enzyme 2 (ACE-2) percent inhibition specific to the BA.4/BA.5 Omicron Ag. Contrary to expectations, our findings revealed that more WT-based vaccines were associated with an enhanced Omicron-specific immune response.

Minimal impact on the resistome of children in Botswana after azithromycin treatment for acute severe diarrhoeal disease.

BACKGROUND: Macrolide antibiotics, including azithromycin, can reduce under-five mortality rates and treat various infections in children in sub-Saharan Africa. These exposures, however, can select for antibiotic-resistant bacteria in the gut microbiota. METHODS: Our previous randomized controlled trial (RCT) of a rapid-test-and-treat strategy for severe acute diarrhoeal disease in children in Botswana included an intervention (three-day azithromycin dose) group and a control group that received supportive treatment. In this prospective matched cohort study using stools collected at baseline and 60 days after treatment from RCT participants, the collection of antibiotic resistance genes or resistome was compared between groups. RESULTS: Certain macrolide resistance genes increased in prevalence by 13% to 55% at 60 days, without differences in gene presence between the intervention and control groups. These genes were linked to tetracycline resistance genes and mobile genetic elements. CONCLUSIONS: Azithromycin treatment for bacterial diarrhoea for young children in Botswana resulted in similar effects on the gut resistome as the supportive treatment and did not provide additional selective pressure for macrolide resistance gene maintenance. The gut microbiota of these children contains diverse macrolide resistance genes that may be transferred within the gut upon repeated exposures to azithromycin or co-selected by other antibiotics.

Factors associated with SARS-CoV-2 infection in unvaccinated children and young adults.

BACKGROUND AND OBJECTIVES: Pediatric COVID-19 cases are often mild or asymptomatic, which has complicated estimations of disease burden using existing testing practices. We aimed to determine the age-specific population seropositivity and risk factors of SARS-CoV-2 seropositivity among children and young adults during the pandemic in British Columbia (BC). METHODS: We conducted two cross-sectional serosurveys: phase 1 enrolled children and adults < 25 years between November 2020-May 2021 and phase 2 enrolled children < 10 years between June 2021-May 2022 in BC. Participants completed electronic surveys and self-collected finger-prick dried blood spot (DBS) samples. Samples were tested for immunoglobulin G antibodies against ancestral spike protein (S). Descriptive statistics from survey data were reported and two multivariable analyses were conducted to evaluate factors associated with seropositivity. RESULTS: A total of 2864 participants were enrolled, of which 95/2167 (4.4%) participants were S-seropositive in phase 1 across all ages, and 61/697 (8.8%) unvaccinated children aged under ten years were S-seropositive in phase 2. Overall, South Asian participants had a higher seropositivity than other ethnicities (13.5% vs. 5.2%). Of 156 seropositive participants in both phases, 120 had no prior positive SARS-CoV-2 test. Young infants and young adults had the highest reported seropositivity rates (7.0% and 7.2% respectively vs. 3.0-5.6% across other age groups). CONCLUSIONS: SARS-CoV-2 seropositivity among unvaccinated children and young adults was low in May 2022, and South Asians were disproportionately infected. This work demonstrates the need for improved diagnostics and reporting strategies that account for age-specific differences in pandemic dynamics and acceptability of testing mechanisms.

Eleven-month SARS-CoV-2 binding antibody decay, and associated factors, among mRNA vaccinees: implications for booster vaccination.

Background: We examined the 11 month longitudinal antibody decay among two-dose mRNA vaccinees, and identified factors associated with faster decay. Methods: The study included samples from the COVID-19 Occupational Risk, Seroprevalence and Immunity among Paramedics (CORSIP) longitudinal observational study of paramedics in Canada. Participants were included if they had received two mRNA vaccines without prior SARS-CoV-2 infection and provided two blood samples post-vaccination. The outcomes of interest were quantitative SARS-CoV-2 antibody concentrations. We employed spaghetti and scatter plots (with kernel-weighted local polynomial smoothing curve) to describe the trend of the antibody decay over 11 months post-vaccine and fit a mixed effect exponential decay model to examine the loss of immunogenicity and factors associated with antibody waning over time. Results: This analysis included 652 blood samples from 326 adult paramedics. Total anti-spike antibody levels peaked on the twenty-first day (antibody level 9042 U ml-1) after the second mRNA vaccine dose. Total anti-spike antibody levels declined thereafter, with a half-life of 94 [95 % CI: 70, 143] days, with levels plateauing at 295 days (antibody level 1021 U ml-1). Older age, vaccine dosing interval <35 days, and the BNT162b2 vaccine (compared to mRNA-1273 vaccine) were associated with faster antibody decay. Conclusion: Antibody levels declined after the initial mRNA series with a half-life of 94 days, plateauing at 295 days. These findings may inform the timing of booster vaccine doses and identifying individuals with faster antibody decay.

The association of post-COVID-related symptoms and preceding SARS-CoV-2 infection among fully vaccinated paramedics in Canada.

This study investigated the association between previous SARS-CoV-2 infection and risk of symptoms associated with post COVID conditions among fully vaccinated paramedics in Canada. We included vaccinated paramedics who provided blood sample and questionnaire data on the same date during the study period. We examined the presence of symptoms associated with post-COVID conditions, depression severity against prior SARS-CoV-2 infection categories. Compared to "no previous SARS-CoV-2 infection" group, there was no detected association between "known prior SARS-CoV-2 infection" (OR: 1.42, 95% CI:0.96-2.09), nor "unknown prior SARS-Cov-2 infection" (OR: 0.54, 95% CI:0.29-1.00), and "the presence of symptoms associated with post-COVID conditions".

Frequent microbiological surveillance during inpatient cystic fibrosis pulmonary exacerbations has limited clinical value.

BACKGROUND: No evidence exists to guide the frequency of obtaining bacterial respiratory cultures during inpatient treatment of pediatric cystic fibrosis (CF) pulmonary exacerbations (PEx). At our institution, admission and weekly respiratory cultures are routinely collected to guide antimicrobial selection. This study evaluates the extent that this practice informs clinical management and the healthcare-related costs associated with routinely repeating cultures. METHODS: All children with CF with at least one hospital admission for IV antibiotics from January 2015 to December 2019 were included. Data collected included patient demographics, culture results, and antibiotic history. Respiratory cultures were numbered from the last clinic culture (`Culture 1'), culture on admission (`Culture 2'), and so on (`Cultures 3-6'). Outcomes assessed were microbiological results, frequency and timing of antibiotic change, and total microbiological laboratory costs. RESULTS: Seventy-eight children with 224 admissions and 695 bacterial cultures were analyzed. Repeated microbiology sampling revealed 118 new bacterial species in 82 admissions.  Culture 2 was most likely to identify a new bacterial species (91/115, 79.1 %) and most likely to be followed by a change in antibiotic (33/37; 89.2 %). The total cost of all cultures was $18,264.79. Eliminating Cultures 3-6 from routine practice could represent a 51 % cost-savings ($9,362.89), without significant impact on identification of new clinically relevant isolates. CONCLUSION: Ongoing bacterial surveillance during a CF PEx beyond admission culture provides minimal information, rarely impacts clinical management, and can increase healthcare costs. An optimized approach would be to routinely obtain admission cultures and to obtain further cultures only if clinically indicated.

Respiratory syncytial virus epidemiology and clinical severity before and during the COVID-19 pandemic in British Columbia, Canada: a retrospective observational study.

Background: The COVID-19 pandemic has perturbed the seasonality of respiratory syncytial virus (RSV) infections. However, we lack data on how this impacted the severity of paediatric RSV cases. The objective of this study was to describe the clinical severity of RSV cases before, during and after pandemic measures in British Columbia (BC), Canada. Methods: Retrospective study of RSV cases from September 1st, 2017 to May 15th, 2023, with a review of RSV outcomes in children below 18 years old at BC's paediatric hospital. Temporal changes in RSV cases and hospitalisations were quantified using interrupted time series. Findings: BC experienced only 11 RSV cases (from 95,266 tests) between September 2020 and August 2021. This was followed by a resurgence of 9,529 RSV cases (219,566 tests [4.3% positive tests]) in 2021-22 and 8,215 cases (124,449 tests [6.6% positive tests]) in 2022-23, increased compared to 1,750 cases (48,664 tests [3.6% positive tests]) per corresponding yearly period in 2017-20. From September 2017 to May 2023, the median age of children with RSV at BC Children's Hospital increased from 8.7 [IQR: 2.0-26.0] to 19.6 [3.9-43.7] months per yearly period. More children were hospitalised in 2022-23 (n = 360), compared to 2017-20 (n = 168 per period) and 2021-22 (n = 172). However, we detected no increase in hospitalisations or ICU admissions in children born prematurely or with chronic cardiorespiratory conditions. Interpretation: The increased detection of symptomatic RSV cases in older children in 2021-22 and increased RSV-related hospitalisations in 2022-23 suggest a gradual increase in the pool of immunologically vulnerable children due to a prolonged lack of viral exposure. Funding: Government of Canada via its COVID-19 Immunity Task Force.

Effect of vaccine dosing intervals on Omicron surrogate neutralization after three doses of BNT162b2.

Background: Increasing the interval between the first and second SARS-CoV-2 vaccine doses enhances vaccine immunogenicity, however the optimal timing of the third vaccine is unknown. In this study, we investigated how the time interval between the first and second (V1-V2), or second and third (V2-V3) doses affects immunogenicity after three doses of the BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine. Methods: This is an observational cohort consisting of 360 participants enrolled in the COVID-19 Occupational Risks, Seroprevalence, and Immunity among Paramedics in Canada (CORSIP) study. Immune responses to BA.1 and other variants were measured from serum using an ACE2 competitive binding assay for surrogate SARS-CoV-2 neutralization. We fit a multiple linear regression model to estimate the independent association between both the V1-V2 and V2-V3 intervals and serum SARS-CoV-2 neutralization, while adjusting for age, sex, and the V3-to-blood collection interval. We examined vaccine dosing intervals as continuous variables and categorized them into quartiles. Results: The mean age was 40 years, 45% were female sex (at birth), and the median BA.1 surrogate neutralization was 61% (IQR 38-77%). The multivariate analysis indicated that longer V1-V2 (ß = 0.1292, 95% CI: 0.04807-0.2104) and V2-V3 (ß = 0.2653, 95% CI: 0.2291-0.3015) intervals were associated with increased surrogate neutralization of BA.1. These results were consistent when examining responses against Spike from other SARS-CoV-2 strains. When categorized into V2-V3 quartiles, the first (56-231 days), and second (231-266 days) quartiles demonstrated decreased BA.1 surrogate neutralization compared to the longest V2-V3 quartile (282-329 days). There was no significant difference in surrogate neutralization between the long (266-282 days) and longest (282-329 days) V2-V3 intervals. Conclusion: Longer intervals between first, second and third doses are independently associated with increased immunogenicity for all tested SARS-CoV-2 strains. Increasing the intervals between the second and third vaccine doses up to 8.9 months provided additive benefits increasing the immunogenicity of BNT162b2 vaccine schedules.

Rapid diagnostic testing for syphilis in Arctic communities (the STAR study): a multisite prospective field diagnostic accuracy study in an intended-use setting.

OBJECTIVES: We evaluated the field diagnostic accuracy of a syphilis rapid test (RDT), using serum and whole blood by non-laboratorians in two Canadian Arctic communities. METHODS: We implemented a multisite prospective field evaluation wherein patients were screened by an RDT containing treponemal and non-treponemal components (Chembio DPP® Syphilis Screen & Confirm) between January 2020 and December 2021. Venous whole blood and serum were collected for rapid testing and compared with laboratory-based serology reference testing using a reverse sequence algorithm of treponemal and rapid plasma reagin (RPR) testing. RESULTS: Overall, 135 whole blood and 139 serum specimens were collected from 161 participants during clinical encounters. Treponemal-RDT sensitivity against a treponemal-reference standard (38/161 confirmed cases) was similar for serum (78% [95% CI: 61-90%]) and whole blood (81% [95% CI: 63-93%]). In those with RPR titres ≥1:8 (i.e. suggestive of recent/active infection), sensitivity increased to 93% (95% CI: 77-99%) for serum and 92% (95% CI: 73-99%) for whole blood. Treponemal-RDT specificity was excellent (99% [95% CI: 95-100%]) for both specimen types. Non-treponemal-RDT sensitivity against RPR was 94% (95% CI: 80-99%) for serum and 79% (95% CI: 60-92%) for whole blood. Sensitivity increased to 100% (95% CI: 88-100%) for serum and 92% (95% CI: 73-99%) for whole blood when RPR titres ≥1:8. RDT performance with whole blood was similar to that with serum. DISCUSSION: Non-laboratorians using the RDT accurately identified individuals with infectious syphilis under real-world conditions in an intended-use setting at the point of care. Implementing the RDT can eliminate treatment delays and may enhance disease control.

SARS-CoV-2 cross-sectional seroprevalence study among public school staff in Metro Vancouver after the first Omicron wave in British Columbia, Canada.

OBJECTIVE: To determine the SARS-CoV-2 seroprevalence among school workers within the Greater Vancouver area, British Columbia, Canada, after the first Omicron wave. DESIGN: Cross-sectional study by online questionnaire, with blood serology testing. SETTING: Three main school districts (Vancouver, Richmond and Delta) in the Vancouver metropolitan area. PARTICIPANTS: Active school staff enrolled from January to April 2022, with serology testing between 27 January and 8 April 2022. Seroprevalence estimates were compared with data obtained from Canadian blood donors weighted over the same sampling period, age, sex and postal code distribution. PRIMARY AND SECONDARY OUTCOMES: SARS-CoV-2 nucleocapsid antibody testing results adjusted for test sensitivity and specificity, and regional variation across school districts using Bayesian models. RESULTS: Of 1850 school staff enrolled, 65.8% (1214/1845) reported close contact with a COVID-19 case outside the household. Of those close contacts, 51.5% (625/1214) were a student and 54.9% (666/1214) were a coworker. Cumulative incidence of COVID-19 positive testing by self-reported nucleic acid or rapid antigen testing since the beginning of the pandemic was 15.8% (291/1845). In a representative sample of 1620 school staff who completed serology testing (87.6%), the adjusted seroprevalence was 26.5% (95% CrI 23.9% to 29.3%), compared with 32.4% (95% CrI 30.6% to 34.5%) among 7164 blood donors. CONCLUSION: Despite frequent COVID-19 exposures reported, SARS-CoV-2 seroprevalence among school staff in this setting remained no greater than the community reference group. Results are consistent with the premise that many infections were acquired outside the school setting, even with Omicron.

Is a Lower Dose of More Bioavailable Iron (18-mg Ferrous Bisglycinate) Noninferior to 60-mg Ferrous Sulfate in Increasing Ferritin Concentrations While Reducing Gut Inflammation and Enteropathogen Detection in Cambodian Women? A Randomized Controlled Noninferiority Trial.

BACKGROUND: Global guidelines recommend untargeted iron supplementation for women in regions of anemia prevalence ≥40%, such as Cambodia. However, the potential harms of untargeted iron on the gut have not been rigorously studied in women and likely vary depending on iron dose and form. OBJECTIVES: We investigated if a lower dose of a highly bioavailable iron amino acid chelate was as effective as the standard dose of iron salts in increasing ferritin concentrations and whether any differences were observed in gut inflammation or enteropathogen detection. METHODS: A double-blind, randomized placebo-controlled noninferiority trial was conducted in Cambodia. Nonpregnant women (n = 480, 18-45 y) were randomly assigned to 60-mg ferrous sulfate, 18-mg ferrous bisglycinate, or placebo for 12 wk. Nonfasting blood and stool specimens were collected at baseline and 12 wk. Ferritin and fecal calprotectin were measured with an ELISA. A molecular assay was used to detect 11 enteropathogens in a random subset of n = 100 women. Generalized linear mixed-effects models were used to estimate the adjusted mean difference in ferritin concentrations at 12 wk (primary outcome), as compared with our 'a priori' noninferiority margin of 20 µg/L. RESULTS: Baseline anemia and iron deficiency prevalence was low (17% and 6%, respectively). The adjusted mean difference in ferritin concentrations between the iron groups was 14.6 (95% confidence interval [CI]: 7.6, 21.6) µg/L. Mean ferritin concentration at 12 wk was higher in the ferrous sulfate (99 [95% CI: 95, 103] µg/L, P < 0.001) than in ferrous bisglycinate (84 [95% CI: 80, 88] µg/L) and placebo groups (78 [95% CI: 74, 82] µg/L). No differences in fecal calprotectin concentrations or enteropathogen detection were observed across groups at 12 wk. CONCLUSIONS: Ferrous bisglycinate (18-mg) was not as effective as ferrous sulfate (60-mg) in increasing ferritin concentrations and did not differentially influence biomarkers of gut health in this predominantly iron-replete population of Cambodian women. This trial was registered at clinicaltrials.gov registry as NCT04017598.

The Effect of Oral Iron Supplementation on Gut Microbial Composition: a Secondary Analysis of a Double-Blind, Randomized Controlled Trial among Cambodian Women of Reproductive Age.

The World Health Organization recommends untargeted iron supplementation for women of reproductive age (WRA) in countries where anemia prevalence is greater than 40%, such as Cambodia. Iron supplements, however, often have poor bioavailability, so the majority remains unabsorbed in the colon. The gut houses many iron-dependent bacterial enteropathogens; thus, providing iron to individuals may be more harmful than helpful. We examined the effects of two oral iron supplements with differing bioavailability on the gut microbiomes in Cambodian WRA. This study is a secondary analysis of a double-blind, randomized controlled trial of oral iron supplementation in Cambodian WRA. For 12 weeks, participants received ferrous sulfate, ferrous bisglycinate, or placebo. Participants provided stool samples at baseline and 12 weeks. A subset of stool samples (n = 172), representing the three groups, were randomly selected for gut microbial analysis by 16S rRNA gene sequencing and targeted real-time PCR (qPCR). At baseline, 1% of women had iron-deficiency anemia. The most abundant gut phyla were Bacteroidota (45.7%) and Firmicutes (42.1%). Iron supplementation did not alter gut microbial diversity. Ferrous bisglycinate increased the relative abundance of Enterobacteriaceae, and there was a trend towards an increase in the relative abundance of Escherichia-Shigella. qPCR detected an increase in the enteropathogenic Escherichia coli (EPEC) virulence gene, bfpA, in the group that received ferrous sulfate. Thus, iron supplementation did not affect overall gut bacterial diversity in predominantly iron-replete Cambodian WRA, however, evidence does suggest an increase in relative abundance within the broad family Enterobacteriaceae associated with ferrous bisglycinate use. IMPORTANCE To the best of our knowledge, this is the first published study to characterize the effects of oral iron supplementation on the gut microbiomes of Cambodian WRA. Our study found that iron supplementation with ferrous bisglycinate increases the relative abundance of Enterobacteriaceae, which is a family of bacteria that includes many Gram-negative enteric pathogens like Salmonella, Shigella, and Escherichia coli. Using qPCR for additional analysis, we were able to detect genes associated with enteropathogenic E. coli, a type of diarrheagenic E. coli known to be present around the world, including water systems in Cambodia. The current WHO guidelines recommend blanket (untargeted) iron supplementation for Cambodian WRA despite a lack of studies in this population examining iron's effect on the gut microbiome. This study can facilitate future research that may inform evidence-based global practice and policy.

Extraction-free clinical detection of SARS-CoV-2 virus from saline gargle samples using Hamilton STARlet liquid handler.

As part of the COVID-19 pandemic, clinical laboratories have been faced with massive increases in testing, resulting in sample collection systems, reagent, and staff shortages. We utilized self-collected saline gargle samples to optimize high throughput SARS-CoV-2 multiplex polymerase chain reaction (PCR) testing in order to minimize cost and technologist time. This was achieved through elimination of nucleic acid extraction and automation of sample handling on a widely available robotic liquid handler, Hamilton STARlet. A customized barcode scanning script for reading the sample ID by the Hamilton STARlet's software system was developed to allow primary tube sampling. Use of pre-frozen SARS-CoV-2 assay reaction mixtures reduced assay setup time. In both validation and live testing, the assay produced no false positive or false negative results. Of the 1060 samples tested during validation, 3.6% (39/1060) of samples required retesting as they were either single gene positive, had internal control failure or liquid aspiration error. Although the overall turnaround time was only slightly faster in the automated workflow (185 min vs 200 min), there was a 76% reduction in hands-on time, potentially reducing staff fatigue and burnout. This described process from sample self-collection to automated direct PCR testing significantly reduces the total burden on healthcare systems in terms of human resources and reagent requirements.

Neonatal Intensive Care Unit Interventions to Improve Breastfeeding Rates at Discharge Among Preterm and Low Birth Weight Infants: A Systematic Review and Meta-Analysis.

Background: While breast milk is widely accepted as the best source of nutrients for almost all newborns, breastfeeding can be especially challenging for preterm and low birth weight (LBW) infants. With increased risk of admission to neonatal intensive care units (NICUs) and separation from parents, this population experiences significant barriers to successful breastfeeding. Thus, it is crucial to identify interventions that can optimize breastfeeding for preterm and LBW infants that is continued from birth and admission, through to hospital discharge and beyond. Objectives: To identify and analyze evidence-based interventions that promote any and exclusive breastfeeding among preterm and LBW neonates at discharge and/or postdischarge from hospital. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. Searches were performed in the following databases: MEDLINE Ovid, EMBASE, Web of Science, and Cumulative Index to Nursing and Allied Health (CINAHL). Results: From the 42 studies included, 6 groups of intervention types were identified: educational and breastfeeding support programs, early discharge, oral stimulation, artificial teats and cups, kangaroo mother care (KMC), and supportive policies within NICUs. All groupings of interventions were associated with significantly increased rates of any breastfeeding at discharge. All types of interventions except artificial teats/cups and oral stimulation showed statistically significant increases in exclusive breastfeeding at discharge. KMC demonstrated the highest increased odds of breastfeeding at discharge among preterm and LBW infants. Conclusions: A variety of effective interventions exist to promote breastfeeding among hospitalized preterm and LBW infants. Hospital settings hold unique opportunities for successful breastfeeding promotion. PROSPERO registration: CRD42021252610.

The Relationship Between Anti-Spike SARS-CoV-2 Antibody Levels and Risk of Breakthrough COVID-19 Among Fully Vaccinated Adults.

The relationship between antibodies to wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens and the risk of breakthrough infections is unclear, especially during circulation of the Omicron strain. We investigated the association of anti-spike and anti-receptor binding domain antibody levels and the risk of subsequent breakthrough coronavirus disease 2019 (COVID-19). We included adult paramedics from an observational cohort study who received 2 mRNA vaccines but did not have COVID-19 before the blood collection. Higher postvaccination antibody levels to wild-type SARS-CoV-2 antigens were associated with a reduced risk of COVID-19. Further research into clinical utility of antibody levels, to inform a threshold for protection and timing of boosters, should be prioritized.

Novel care pathway to optimise antimicrobial prescribing for uncomplicated community-acquired pneumonia: study protocol for a prospective before-after cohort study in the emergency department of a tertiary care Canadian children's hospital.

INTRODUCTION: Evidence-based recommendations for paediatric community-acquired pneumonia (CAP) diagnosis and management are needed. Uncomplicated CAP is often caused by respiratory viruses, especially in younger children; these episodes self-resolve without antibiotic treatment. Unfortunately, there are no clinical criteria that reliably discriminate between viral and bacterial disease, and so the majority of children diagnosed with CAP are given antibiotics-even though these will often not help and may cause harm. We have developed a novel care pathway that incorporates point-of-care biomarkers, radiographic patterns, microbiological testing and targeted follow-up. The primary study objective is to determine if the care pathway will be associated with less antimicrobial prescribing. METHODS AND ANALYSIS: A prospective, before-after, study. Previously well children aged≥6 months presenting to a paediatric emergency department (ED) that have at least one respiratory symptom/sign, receive chest radiography, and are diagnosed with CAP by the ED physician will be eligible. Those with medical comorbidities, recently diagnosed pulmonary infection, or ongoing fever after≥4 days of antimicrobial therapy will be excluded. In the control (before) phase, eligible participants will be managed as per the standard of care. In the intervention (after) phase, eligible participants will be managed as per the novel care pathway. The primary outcome will be the proportion of participants in each phase who receive antimicrobial treatment for CAP. The secondary outcomes include: clinical cure; re-presentation to the ED; hospitalisation; time to resolution of symptoms; drug adverse events; caregiver satisfaction; child absenteeism from daycare/school; and caregiver absenteeism from work. ETHICS AND DISSEMINATION: All study documentation has been approved by the Hamilton Integrated Research Ethics Board and informed consent will be obtained from all participants. Data from this study will be presented at major conferences and published in peer-reviewed publications to facilitate collaborations with networks of clinicians experienced in the dissemination of clinical guidelines. TRIAL REGISTRATION NUMBER: NCT05114161.

Characterizing Longitudinal Antibody Responses in Recovered Individuals Following COVID-19 Infection and Single-Dose Vaccination: A Prospective Cohort Study.

BACKGROUND: Investigating antibody titers in individuals who have been both naturally infected with SARS-CoV-2 and vaccinated can provide insight into antibody dynamics and correlates of protection over time. METHODS: Human coronavirus (HCoV) IgG antibodies were measured longitudinally in a prospective cohort of qPCR-confirmed, COVID-19 recovered individuals (k = 57) in British Columbia pre- and post-vaccination. SARS-CoV-2 and endemic HCoV antibodies were measured in serum collected between Nov. 2020 and Sept. 2021 (n = 341). Primary analysis used a linear mixed-effects model to understand the effect of single dose vaccination on antibody concentrations adjusting for biological sex, age, time from infection and vaccination. Secondary analysis investigated the cumulative incidence of high SARS-CoV-2 anti-spike IgG seroreactivity equal to or greater than 5.5 log10 AU/mL up to 105 days post-vaccination. No re-infections were detected in vaccinated participants, post-vaccination by qPCR performed on self-collected nasopharyngeal specimens. RESULTS: Bivariate analysis (complete data for 42 participants, 270 samples over 472 days) found SARS-CoV-2 spike and RBD antibodies increased 14-56 days post-vaccination (p < 0.001) and vaccination prevented waning (regression coefficient, B = 1.66 [95%CI: 1.45-3.46]); while decline of nucleocapsid antibodies over time was observed (regression coefficient, B = -0.24 [95%CI: -1.2-(-0.12)]). A positive association was found between COVID-19 vaccination and endemic human ß-coronavirus IgG titer 14-56 days post vaccination (OC43, p = 0.02 & HKU1, p = 0.02). On average, SARS-CoV-2 anti-spike IgG concentration increased in participants who received one vaccine dose by 2.06 log10 AU/mL (95%CI: 1.45-3.46) adjusting for age, biological sex, and time since infection. Cumulative incidence of high SARS-CoV-2 spike antibodies (>5.5 log10 AU/mL) was 83% greater in vaccinated compared to unvaccinated individuals. CONCLUSIONS: Our study confirms that vaccination post-SARS-CoV-2 infection provides multiple benefits, such as increasing anti-spike IgG titers and preventing decay up to 85 days post-vaccination.