The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism ...proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms.
Selected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020–March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination (“controls”) were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay (DCBA). Anti-PEG IgG and IgM were measured using two different assays: DCBA and a PEGylated-polystyrene bead assay. Laboratorians were blinded to case/control status.
All 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65 %) were hospitalized and 7 (35 %) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10 %) case-patients vs 8 of 30 (27 %) controls (p = 0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0 %) vs 1 of 30 (3 %) controls (p >n 0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats.
Our results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination.
Abstract
Background
The 2019–2020 influenza season was characterized by early onset with B/Victoria followed by A(H1N1)pdm09 viruses. Emergence of new B/Victoria viruses raised concerns about ...possible vaccine mismatch. We estimated vaccine effectiveness (VE) against influenza-associated hospitalizations and emergency department (ED) visits among children in the United States.
Methods
We assessed VE among children aged 6 months–17 years with acute respiratory illness and ≤10 days of symptoms enrolled at 7 pediatric medical centers in the New Vaccine Surveillance Network. Combined midturbinate/throat swabs were tested for influenza virus using molecular assays. Vaccination history was collected from parental report, state immunization information systems, and/or provider records. We estimated VE from a test-negative design using logistic regression to compare odds of vaccination among children testing positive vs negative for influenza.
Results
Among 2029 inpatients, 335 (17%) were influenza positive: 37% with influenza B/Victoria alone and 44% with influenza A(H1N1)pdm09 alone. VE was 62% (95% confidence interval CI, 52%–71%) for influenza-related hospitalizations, 54% (95% CI, 33%–69%) for B/Victoria viruses, and 64% (95% CI, 49%–75%) for A(H1N1)pdm09. Among 2102 ED patients, 671 (32%) were influenza positive: 47% with influenza B/Victoria alone and 42% with influenza A(H1N1)pdm09 alone. VE was 56% (95% CI, 46%–65%) for an influenza-related ED visit, 55% (95% CI, 40%–66%) for B/Victoria viruses, and 53% (95% CI, 37%–65%) for A(H1N1)pdm09.
Conclusions
Influenza vaccination provided significant protection against laboratory-confirmed influenza-associated hospitalizations and ED visits associated with the 2 predominantly circulating influenza viruses among children, including against the emerging B/Victoria virus subclade.
In the New Vaccine Surveillance Network of 7 US pediatric medical centers, influenza vaccine effectiveness was 62% (95% confidence interval CI, 52%–71%) and 56% (95% CI, 46%–65%) against influenza-related hospitalizations and ED visits, respectively, protecting against B/Victoria and A(H1N1)pdm09 viruses.
Human coronaviruses (HCoVs) have been detected in children with upper and lower respiratory symptoms, but little is known about their relationship with severe respiratory illness.
To compare the ...prevalence of HCoV species among children hospitalized for acute respiratory illness and/or fever (ARI/fever) with that among asymptomatic controls and to assess the severity of outcomes among hospitalized children with HCoV infection compared with other respiratory viruses.
From December 2003 to April 2004 and October 2004 to April 2005, we conducted prospective, population-based surveillance of children <5 years of age hospitalized for ARI/fever in 3 US counties. Asymptomatic outpatient controls were enrolled concurrently. Nasal/throat swabs were tested for HCoV species HKU1, NL63, 229E, and OC43 by real-time reverse-transcription polymerase chain reaction. Specimens from hospitalized children were also tested for other common respiratory viruses. Demographic and medical data were collected by parent/guardian interview and medical chart review.
Overall, HCoV was detected in 113 (7.6%) of 1481 hospitalized children (83 5.7% after excluding 30 cases coinfected with other viruses) and 53 (7.1%) of 742 controls. The prevalence of HCoV or individual species was not significantly higher among hospitalized children than controls. Hospitalized children testing positive for HCoV alone tended to be less ill than those infected with other viruses, whereas those coinfected with HCoV and other viruses were clinically similar to those infected with other viruses alone.
In this study of children hospitalized for ARI/fever, HCoV infection was not associated with hospitalization or with increased severity of illness.
Since diarrheagenic
E. coli are not identified by common clinical laboratory techniques, we hypothesized that these organisms might be an unrecognized cause of enteritis in children in the U.S.
1327 ...children with acute gastroenteritis were identified prospectively by active surveillance in the Emergency Department (ED) and the inpatient units at Cincinnati Children's Hospital Medical Center. Stool samples were evaluated for diarrheagenic
E. coli using a panel of DNA probes and adherence pattern to HEp-2 cells. Stool samples from a reference group of 555 well children were studied for comparison.
Gene probe studies, but not HEp-2 cell adherence, demonstrated that enteroaggregative, diffusely adherent and enteropathogenic
E. coli were associated with clinical illness. Each was isolated significantly more often from study subjects in the ED than controls. In children <1 year of age, enteroaggregative
E. coli were isolated significantly more often from both inpatients (4.7%, Odds Ratio
=
3.4, 95% confidence intervals 1.3-9.1, p <0.03) and ED patients (10.0%, Odds Ratio
=
7.2, 95% confidence intervals 2.9-18.2, p <0.001) than from well children (1.4%).
Diarrheagenic
E. coli, especially enteroaggregative
E. coli, may be an important, unrecognized cause of childhood diarrhea in the U.S.
Abstract
Studies have shown egg-adaptive mutations in influenza vaccine strains that might have impaired protection against circulating A(H3N2) influenza viruses during the 2016–2017 and 2017–2018 ...seasons. We used the test-negative design and multivariable models to assess vaccine effectiveness against influenza-associated hospitalization and emergency department visits among children (<18 years old) during the 2016–2017 and 2017–2018 seasons. Effectiveness was 71% (95% confidence interval, 59%–79%), 46% (35%–55%), and 45% (33%–55%) against A(H1N1)pdm09, A(H3N2), and B viruses respectively, across both seasons. During high-severity seasons with concerns for vaccine mismatch, vaccination offered substantial protection against severe influenza outcomes requiring hospitalization or emergency department visits among children.
With use of the test-negative design to evaluate influenza vaccine effectiveness, vaccination in the 2016–2017 and 2017–2018 seasons halved the risk of children requiring hospitalization or emergency department visits owing to influenza-related illness.
Adjuvanted inactivated influenza vaccine (aIIV) and high-dose inactivated influenza vaccine (HD-IIV) are U.S.-licensed for adults aged ≥ 65 years. This study compared serum hemagglutination ...inhibition (HAI) antibody titers for the A(H3N2) and A(H1N1)pdm09 and B strains after trivalent aIIV3 and trivalent HD-IIV3 in an older adult population.
The immunogenicity population included 342 participants who received aIIV3 and 338 participants who received HD-IIV3. The proportion of participants that seroconverted to A(H3N2) vaccine strains after allV3 (112 participants 32.8%) was inferior to the proportion of participants that seroconverted after HD-IIV3 (130 participants 38.5%) at day 29 after vaccination (difference, - 5.8%; 95%CI, - 12.9% to 1.4%). There were no significant differences between the vaccine groups in percent seroconversion to A(H1N1)pdm09 or B vaccine strains, in percent seropositivity for any of the strains, or in post-vaccination GMT for the A(H1N1)pdm09 strain. The GMTs for the post-vaccination A(H3N2) and B strains were higher after HD-IIV than after aIIV3.
Overall immune responses were similar after aIIV3 and HD-IIV3. For the primary outcome, the aIIV3 seroconversion rate for H3N2 did not meet noninferiority criteria compared with HD-IIV3, but the HD-IIV3 seroconversion rate was not statistically superior to the aIIV3 seroconversion rate.
ClinicalTrials.gov Identifier: NCT03183908.
Respiratory syncytial virus (RSV) is the leading cause of hospitalization in US infants. Accurate estimates of severe RSV disease inform policy decisions for RSV prevention.
We conducted prospective ...surveillance for children <5 years old with acute respiratory illness from 2016 to 2020 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested midturbinate nasal ± throat swabs by reverse transcription polymerase chain reaction for RSV and other respiratory viruses. We describe characteristics of children hospitalized with RSV, risk factors for ICU admission, and estimate RSV-associated hospitalization rates.
Among 13 524 acute respiratory illness inpatients <5 years old, 4243 (31.4%) were RSV-positive; 2751 (64.8%) of RSV-positive children had no underlying condition or history of prematurity. The average annual RSV-associated hospitalization rate was 4.0 (95% confidence interval CI: 3.8-4.1) per 1000 children <5 years, was highest among children 0 to 2 months old (23.8 95% CI: 22.5-25.2 per 1000) and decreased with increasing age. Higher RSV-associated hospitalization rates were found in premature versus term children (rate ratio = 1.95 95% CI: 1.76-2.11). Risk factors for ICU admission among RSV-positive inpatients included: age 0 to 2 and 3 to 5 months (adjusted odds ratio aOR = 1.97 95% CI: 1.54-2.52 and aOR = 1.56 95% CI: 1.18-2.06, respectively, compared with 24-59 months), prematurity (aOR = 1.32 95% CI: 1.08-1.60) and comorbid conditions (aOR = 1.35 95% CI: 1.10-1.66).
Younger infants and premature children experienced the highest rates of RSV-associated hospitalization and had increased risk of ICU admission. RSV prevention products are needed to reduce RSV-associated morbidity in young infants.
Few U.S. women meet the public health recommendations to exclusively breastfeed for 6 months and continue breastfeeding for at least 1-2 years. We compared prenatally collected demographic, health, ...and breastfeeding support/intention variables to examine how these factors intersect to predict meeting breastfeeding recommendations.
PREVAIL, a CDC-funded birth cohort in Cincinnati, OH, was approved by the IRB at CDC, Cincinnati Children's Hospital, and the hospitals where enrollment (third trimester, 2017-2018) occurred. The prenatal questionnaire captured sociodemographics, pre-pregnancy weight and height, breastfeeding environment, and breastfeeding intention, while health factors were obtained from obstetrical records. Body mass index (BMI) (kg/m
) was categorized as healthy (18.5-24.9), overweight (25-29.9), obesity 1 (30-34.9), and obesity 2+ (≥35). Mothers self-reported date of exclusive and any breastfeeding cessation through quarterly postnatal questionnaires. Random forest was used for variable selection, cross-validated in multivariable logistic models.
Analysis included
= 237 mothers with BMI ≥18.5. Random forest identified BMI category, prenatal intention, and insurance type as the most important predictors of meeting breastfeeding recommendations. The resulting logistic models explained >40% of the variance with an area under the curve of ≥0.89 for both recommendations. More than 73% of the risk of not meeting breastfeeding recommendations was attributable to having an elevated BMI or lacking strong breastfeeding intention.
In PREVAIL, maternal BMI and prenatal intention explained most risks of not meeting breastfeeding exclusivity and duration recommendations. Our findings suggest efforts to improve breastfeeding exclusivity and duration should focus on strengthening prenatal breastfeeding intention and identifying effective interventions for supporting breastfeeding among mothers with higher BMI.
Influenza rapid antigen detection (rapid tests) can provide timely identification of infection and aid in clinical decision-making. Although the interpretation of test results depends on test ...characteristics and influenza prevalence, this information is limited in routine clinical practice.
We sought to assess the times at which rapid tests are most predictive of influenza infection.
The New Vaccine Surveillance Network enrolled children aged < 5 years who were hospitalized with respiratory symptoms or fever from October 2000 through September 2004. Nasal and throat swabs were obtained, and influenza virus was detected by culture and reverse-transcription polymerase chain reaction. Provider-ordered rapid influenza tests were compared with the criterion standard (culture and reverse-transcription polymerase chain reaction) to determine their sensitivity and specificity. The New Vaccine Surveillance Network also enrolled children in outpatient settings during the 2002-2003 and 2003-2004 influenza seasons and determined the weekly influenza prevalence among symptomatic children. Trends in weekly predictive values of the rapid tests were estimated over the influenza seasons.
Rapid influenza tests had an overall sensitivity of 63% and specificity of 97%. In 2002-2003, the prevalence of influenza in symptomatic outpatient children peaked at 21% and stayed above 10% for approximately 4 weeks. In contrast, in 2003-2004, influenza prevalence peaked at 60% and remained above 20% for approximately 6 weeks. The positive predictive value of the rapid tests approached 80% when influenza prevalence was > or = 15% but decreased to < 70% when influenza prevalence was < 10%.
Influenza prevalence varies between and within seasons. On the basis of our estimates, rapid tests are of limited use when prevalence is < 10%. The appropriate interpretation of rapid influenza tests requires local influenza surveillance and timely communication of this information to the practitioners.
Abstract
Multisystem inflammatory syndrome in children (MIS-C) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; in the United States, reporting of MIS-C ...after coronavirus disease 2019 (COVID-19) vaccination is required for vaccine safety monitoring. Pfizer-BioNTech COVID-19 vaccine was authorized for children aged 5−11 years on 29 October 2021. Covering a period when approximately 7 million children received vaccine, surveillance for MIS-C ≤ 90 days postvaccination using passive systems identified 58 children with MIS-C and laboratory evidence of past/recent SARS-CoV-2 infection, and 4 without evidence. During a period with extensive SARS-CoV-2 circulation, MIS-C illness in children after COVID-19 vaccination who lacked evidence of SARS-CoV-2 infection was rare (<1 per million vaccinated children).
Covering a period when approximately 7 million children aged 5–11 years received Pfizer-BioNTech COVID-19 vaccine, passive surveillance for MIS-C ≤ 90 days postvaccination identified 58 children with MIS-C and laboratory evidence of past or recent SARS-CoV-2 infection, and 4 without evidence.
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