James D. Campbell

Background: Cell-mediated immunity (CMI) may help protect against emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that are less susceptible to neutralizing antibodies. We present CMI data after the mRNA-1273 primary series in a subset of participants aged 6 months to 11 years from the phase 2/3 KidCOVE trial. Methods: T-cell responses were assessed after 2 doses of mRNA-1273 (6 months to 5 years, 25 μg; 6–11 years, 50 μg) or placebo administered 28 days apart. Magnitude, phenotype, and percentage of ancestral SARS-CoV-2 spike (S) protein T-cell responses to pooled peptides were assessed by intracellular cytokine staining and polyfunctionality analyses. Results: A total of 68 children aged 6 months to 11 years received either the 2-dose mRNA-1273 primary series or placebo (51 and 17, respectively) at 28-day interval. mRNA-1273 induced S-protein–specific CD4+ T-cell responses exhibiting a type 1 T helper (Th1)–biased profile at day 43 and day 209 compared with placebo. S-protein–specific CD8+ T-cell responses were less frequently detected in children <5 years and undetectable in those <2 years. Compared with placebo, mRNA-1273 induced higher frequencies of S-specific polyfunctional CD4+ T cells at day 43; frequencies declined but remained detectable at day 209. Correlation between Th1 CD4+ responses and neutralizing antibodies was observed across age groups following mRNA-1273 vaccination. Conclusions: The 2-dose mRNA-1273 primary series elicited robust and durable (≥ 6 months) Th1-biased CD4+ T-cell responses in children aged 6 months to 11 years. CD8+ T-cell responses varied by age. Clinical Trials Registration. NCT04796896.

OBJECTIVES: To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC₂₄/MIC) greater than or equal to 400. DESIGN: Prospective population pharmacokinetic study of vancomycin. SETTING: Critically ill patients in quaternary care PICUs. PATIENTS: Children 90 days old or older to younger than 18 years who received IV vancomycin treatment, irrespective of the indication for use, in the ICUs at the University of Maryland Children’s Hospital and Texas Children’s Hospital were enrolled. INTERVENTIONS: Vancomycin was prescribed at doses and intervals chosen by the treating clinicians. MEASUREMENTS AND MAIN RESULTS: A median of four serum levels of vancomycin per patient were collected along with other variables for up to 7 days following the first administration. These data were used to characterize vancomycin pharmacokinetics and evaluate the factors affecting the variability in achieving AUC₂₄/MIC ratio greater than or equal to 400 in PICU patients who are not on extracorporeal therapy. A total of 302 children with a median age of 6.0 years were enrolled. A two-compartment model described the pharmacokinetics of vancomycin with the clearance of 2.76 L/hr for a typical patient weighing 20 kg. The glomerular filtration rate estimated using either the bedside Schwartz equation or the chronic kidney disease in children equation was the only statistically significant predictor of clearance among the variables evaluated, exhibiting equal predictive performance. The trough levels achieving AUC₂₄/MIC = 400 were 5.6–10.0 μg/mL when MIC = 1 μg/mL. The target of AUC₂₄/MIC greater than or equal to 400 was achieved in 60.4% and 36.5% with the typical dosing regimens of 15 mg/kg every 6 and 8 hours (q6h and q8h), respectively. CONCLUSIONS: The pharmacokinetics of vancomycin in critically ill children were dependent on the estimated glomerular filtration rate only. Trough concentrations accurately predict AUC₂₄. Typical pediatric vancomycin dosing regimens of 15 mg/kg q6h and q8h will often lead to AUC₂₄/MIC under 400.

Little is known about parental awareness of multisystem inflammatory syndrome in children (MIS-C), a rare but severe sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Via a nationally representative, cross-sectional survey of US parents conducted via Ipsos KnowledgePanel from October to November 2021, we used bivariate and multivariable analyses to describe and identify demographic variables associated with parental knowledge of and attitudes toward MIS-C and to examine associations with perceived coronavirus disease 2019 (COVID-19) severity and susceptibility. Response rate was 64.2% (3230/5034). Thirty-two percent of respondents had heard of MIS-C. After adjustment, higher educational level (compared to high school degree; some college: odds ratio [OR], 2.00 [95% confidence interval {CI}, 1.44–2.77]; bachelor's degree or higher: OR, 3.14 [95% CI, 2.26–4.35]), being a healthcare worker (OR, 1.82 [95% CI, 1.37–2.42]), having a child with a chronic medical condition (OR, 1.62 [95% CI, 1.22–2.14]), and experience with more severe COVID-19 (OR, 1.46 [95% CI, 1.14–1.86]) were associated with MIS-C awareness. Respondents with a child aged 12–17 years were less likely to be aware of MIS-C compared to those without (OR, 0.78 [95% CI, .63–.96]), as were male respondents (OR, 0.56 [95% CI, .46–.69]) and respondents aged 18–34 years (OR, 0.72 [95% CI, .54–.94]) compared to those aged 35–44 years. Awareness of MIS-C was associated with higher perceived COVID-19 severity and susceptibility (regression coefficients, 0.18 [95% CI, .10–.25], P < .001; 0.19 [95% CI, .11–.28], P < .001, respectively). This survey highlights the need to increase parental awareness of MIS-C. Future studies should explore how education regarding MIS-C as a complication of SARS-CoV-2 infection could improve understanding of pediatric disease severity and susceptibility.

Respiratory syncytial virus (RSV) is the most common cause of early childhood lower respiratory tract infection (LRTI) in low- and middle-income countries (LMICs). Maternal vaccines, birth-dose extended half-life monoclonal antibodies (mAbs), and pediatric vaccines are under development for prevention of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children. We analyzed the health and economic impact of RSV interventions used alone or in combinations in Mali. We modeled age-specific and season-specific risks of RSV LRTI in children through three years, using WHO Preferred Product Characteristics and data generated in Mali. Health outcomes included RSV LRTI cases, hospitalizations, deaths, and disability-adjusted life-years (DALYs). We identified the optimal combination of products across a range of scenarios. We found that mAb delivered at birth could avert 878 DALYs per birth cohort at an incremental cost-effectiveness ratio (ICER) of $597 per DALY averted compared to no intervention if the product were available at $1 per dose. Combining mAb with pediatric vaccine administered at 10/14 weeks, 1947 DALYs would be prevented. The ICER of this combination strategy is $1514 per DALY averted compared to mAb alone. Incorporating parameter uncertainty, mAb alone is likely to be optimal from the societal perspective at efficacy against RSV LRTI above 66%. The optimal strategy was sensitive to economic considerations, including product prices and willingness-to-pay for DALYs. For example, the combination of mAb and pediatric vaccine would be optimal from the government perspective at a willingness-to-pay above $775 per DALY. Maternal vaccine alone or in combination with other interventions was never the optimal strategy, even for high vaccine efficacy. The same was true for pediatric vaccine administered at 6/7 months. At prices comparable to existing vaccine products, extended half-life RSV mAbs would be impactful and efficient components of prevention strategies in LMICs such as Mali.

Background: Little was known about US parental attitudes, beliefs, and intentions surrounding coronavirus disease 2019 (COVID-19) vaccines for children before their introduction. Methods: An online cross-sectional nationally representative survey of US parents/guardians of children < 18 years old via Ipsos KnowledgePanel, fielded from October 26, 2021 to November 30, 2021. Results: Response rate was 64.2% (3230/5034). For children ages 0–4 years, 51.5% of parents were likely to have their children vaccinated, and for ages 5–11 and 12–17, 54.0% and 69.7% of parents, respectively, reported they were likely to vaccinate or had already vaccinated their children. Among respondents with unvaccinated children, 25.2% (ages 0–4) and 22.0% (ages 5–11) reported they would seek COVID-19 vaccination for their children as soon as authorization occurred. Factors associated with willingness to have children receive a COVID-19 vaccine were: belief in benefits of COVID-19 vaccination (odds ratio [OR] = 6.44, 5.68, 4.57 in ages 0–4, 5–11, and 12–17 respectively), acceptance of routine childhood vaccines (OR = 6.42, 5.48, 1.76), parental COVID-19 vaccination (OR = 1.85, 3.70, 6.16), perceptions that pediatric COVID-19 is severe (OR = 1.89, 1.72, 1.35), Hispanic ethnicity (OR = 2.07, 2.29, 2.60), influenza vaccine acceptance (OR = 1.07, 0.88, 1.62), presence of children of another age group in the household (OR = 0.71, 0.71, 0.65), and attitudinal barriers to COVID-19 vaccination (OR = 0.30, 0.26, 0.49). Conclusions: Belief in the benefits of COVID-19 vaccination and acceptance of routine childhood vaccines are the strongest predictors of intention to vaccinate children. Further research is needed to track how parental attitudes change as more data about pediatric COVID-19 vaccines become available and how intentions translate into pediatric vaccine uptake.

SARS-CoV-2 continues to develop new, increasingly infectious variants, such as delta and omicron. Here, we evaluate the efficacy of the Abbott BinaxNOW Rapid Antigen Test against the gold standard of Reverse Transcription Polymerase Chain Reaction (“RT-PCR”) in 1054 pediatric participants presenting to a state-owned high-volume Coronavirus Disease 2019 (COVID-19) testing site. During the testing period, the delta variant was predominant. Prior to sample collection, symptomatic and exposure status was collected for all participants based on Centers for Disease Control (CDC) criteria. RT-PCR results demonstrated an overall prevalence rate of 5.2%. For all participants, the sensitivity of the rapid antigen tests was 92.7% (95% CI 82.4% - 98.0%) and specificity was 98.0% (95% CI 97.0%-98.8%). For symptomatic participants, the sensitivity was 92.3% (95% CI 74.9% - 99.1%), specificity was 96.6% (95% CI 93.6%-98.4%), positive predictive value (PPV) was 72.7% (95% CI 54.5% - 86.7%) and negative predictive value (NPV) was 99.2% (95% CI 98.2% - 100%). Among asymptomatic participants, the sensitivity was 92.6% (95% CI 75.7% - 99.1%), specificity was 98.6% (95% CI 97.5% - 99.3%) the PPV was 71.4% (95% CI 53.7% - 85.4%) and the NPV was 99.7% (95% CI 99.0% - 100%). Our reported sensitivity and NPV are higher than other pediatric studies, but specificity and PPV are lower. Importance Children are especially impacted by the disease and its ability to disrupt educational opportunities. Although vaccinations have been approved for children 5 years and older, many children remain unvaccinated. Widespread testing may improve the ability for children to remain in in-person activities, minimizing absences from school and extracurriculars. Highly accurate rapid antigen tests may be vital to containing future COVID-19 waves while mitigating detrimental effects.