Trends in Disease Severity Among Critically Ill Children With Severe Acute Respiratory Syndrome Coronavirus 2: A Retrospective Multicenter Cohort Study in the United States.

OBJECTIVES: To describe trends in critical illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children over the course of the COVID-19 pandemic. We hypothesized that PICU admission rates were higher in the Omicron period compared with the original outbreak but that fewer patients needed endotracheal intubation. DESIGN: Retrospective cohort study. SETTING: This study took place in nine U.S. PICUs over 3 weeks in January 2022 (Omicron period) compared with 3 weeks in March 2020 (original period). PATIENTS: Patients less than or equal to 21 years old who screened positive for SARS-CoV-2 infection by polymerase chain reaction or hospital-based rapid antigen test and were admitted to a PICU or intermediate care unit were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 267 patients (239 Omicron and 28 original) were reviewed. Forty-five patients in the Omicron cohort had incidental SARS-CoV-2 and were excluded from analysis. The Omicron cohort patients were younger compared with the original cohort patients (median [interquartile range], 6 yr [1.3-13.3 yr] vs 14 yr [8.3-17.3 yr]; p = 0.001). The Omicron period, compared with the original period, was associated with an average increase in COVID-19-related PICU admissions of 13 patients per institution (95% CI, 6-36; p = 0.008), which represents a seven-fold increase in the absolute number admissions. We failed to identify an association between cohort period (Omicron vs original) and odds of intubation (odds ratio, 0.7; 95% CI, 0.3-1.7). However, we cannot exclude the possibility of up to 70% reduction in intubation. CONCLUSIONS: COVID-19-related PICU admissions were seven times higher in the Omicron wave compared with the original outbreak. We could not exclude the possibility of up to 70% reduction in use of intubation in the Omicron versus original epoch, which may represent differences in PICU/hospital admission policy in the later period, or pattern of disease, or possibly the impact of vaccination.

Optimizing Vancomycin Dosing and Monitoring in Neonates and Infants Using Population Pharmacokinetic Modeling.

We determined optimal vancomycin starting dose regimens in infants ≤180 days of age to achieve the highest probability of target attainment with an area under the concentration-time curve for 24 h (AUC24) of ≥400 using population pharmacokinetic (PK) modeling. Secondarily, determination of the relationship between serum creatinine (SCR) and vancomycin clearance in neonates was done. A retrospective population PK study was designed and included pediatric patients ≤180 days old who had received vancomycin and had a serum vancomycin concentration sampled. A population PK model was developed using Pumas (v1.0.5). Simulation was performed with various dosing regimens to evaluate the probability of AUC24 target attainment and probability of trough of ≤20 mg/liter, and comparison to published models was performed. Individual clearance estimates, obtained from the final model, were plotted against SCR and faceted by age quartiles to assess the relationship between SCR and vancomycin clearance. A total of 934 patients were included in the study (58.6% male; median age, 43.6 days [range of 0 to 184]; median number of concentration samples, 1 [range of 1 to 29]). A one-compartment model was developed with body weight (WT), SCR, and postmenstrual age (PMA) identified as significant covariates on clearance. Plotting vancomycin clearance versus SCR demonstrated no clear relationship between the two at <10 days postnatal age (PNA). Dosing regimens to attain AUC24 and trough targets were stratified according to SCR for ≥10 days PNA and PMA for <10 days PNA. A vancomycin population PK model was developed for pediatric patients <180 days of age incorporating WT, SCR, and PMA. The relationship between vancomycin clearance and serum creatinine is not clear at <10 days PNA.

Measles, mumps, rubella (vaccine) and varicella vaccines in pediatric liver transplant: An initial analysis of post-transplant immunity.

Varicella and measles infection represents a significant source of morbidity and mortality for pediatric LT recipients. We evaluated the prevalence and correlates of post-transplant immunity in pediatric LT recipients previously immunized against measles (n = 72) and varicella (n = 67). Sixteen of seventy-two (22%) patients were measles non-immune, and 42/67 (63%) were varicella non-immune after LT. Median time from LT to titers for measles and varicella was 4.0 and 3.3 years, respectively. In the measles cohort, non-immune patients received fewer pretransplant vaccine doses (P = 0.026) and were younger at both time of vaccination (P = 0.006) and LT (P = 0.004) compared with immune patients. Upon multivariable analysis, weight > 10 kg at LT (OR 5.91, 95% CI 1.27-27.41) and technical variant graft (OR 0.07, 95% CI 0.01-0.37) were independently, significantly associated with measles immunity. In the varicella cohort, non-immune patients received fewer pretransplant vaccine doses (P = 0.028), were younger at transplant (P = 0.022), and had less time lapse between their last vaccine and transplant (P = 0.012) compared with immune patients. Upon multivariate analysis, time > 1 year from last vaccine to LT was independently, significantly associated with varicella immunity (OR 3.78, CI 1.30-11.01). This study demonstrates that non-immunity to measles and varicella is a prevalent problem after liver transplantation in children and identifies 3 unique risk factors for non-immunity in this high-risk population.

The half-life of maternal transplacental antibodies against diphtheria, tetanus, and pertussis in infants: an individual participant data meta-analysis.

AIM: There are few reliable estimates of the half-lives of maternal antibodies to the antigens found in the primary series vaccines. We aimed to calculate the half-lives of passively acquired diphtheria, tetanus and pertussis (DTP) antibodies in infants. We aimed to determine whether decay rates varied according to country, maternal age, gestational age, birthweight, World Bank income classifications, or vaccine received by the mother during pregnancy. METHODS: De-identified data from infants born to women taking part in 10 studies, in 9 countries (UK, Belgium, Thailand, Vietnam, Canada, Pakistan, USA, Guatemala and the Netherlands) were combined in an individual participant data meta-analysis. Blood samples were taken at two timepoints before any DTP-containing vaccines were received by the infant: at birth and at 2-months of age. Decay rates for each antigen were log2-transformed and a mixed effects model was applied. Half-lives were calculated by taking the reciprocal of the absolute value of the mean decay rates. RESULTS: Data from 1426 mother-infant pairs were included in the analysis. The half-lives of the 6 antigen-specific maternal antibodies of interest were similar, with point estimates ranging from 28.7 (95% CI: 24.4 - 35) days for tetanus toxoid antibodies to 35.1 (95% CI: 30.7 - 41.1) days for pertactin antibodies. The decay of maternal antibodies did not significantly differ by maternal age, gestational age, birthweight, maternal vaccination status or type of vaccine administered. CONCLUSION: Maternal antibodies decay at different rates for the different antigens; however, the magnitude of the difference is small. Decay rates are not modified by key demographic or vaccine characteristics.

Transmission of Bordetella pertussis to young infants.

BACKGROUND: Pertussis vaccination has reduced the number of notified cases in industrialized countries from peak years by more than 95%. The effect of recently recommended adult and adolescent vaccination strategies on infant pertussis depends, in part, on the proportion of infants infected by adults and adolescents. This proportion, however, remains unclear, because studies have not been able to determine the source case for 47%-60% of infant cases. METHODS: A prospective international multicenter study was conducted of laboratory confirmed infant pertussis cases (aged