Updated guidance regarding the risk of allergic reactions to COVID-19 vaccines and recommended evaluation and management: A GRADE assessment and international consensus approach.

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history.

Atopic outcomes at 2 years in the CORAL cohort, born in COVID-19 lockdown.

INTRODUCTION: The CORAL study is a cohort of infants born during the first weeks of the first SARS-CoV-2 (COVID-19) lockdown. This cohort has had lower antibiotic exposure, higher breastfeeding rates and lower infection rates, especially in the first year of life. We hypothesized that the altered early-life environment of infants born during lockdown would change the incidence of allergic conditions. METHODS: This longitudinal, observational study followed 365 infants born between March and May 2020 from enrolment to the age of 2 years. Infants attended three research appointments at 6-, 12-, and 24-months and completed detailed questionnaires. At research appointments, children had skin prick testing, and atopic dermatitis (AD) assessment. Statistical analysis focused on changes within the group at different time points, the influence of specific environmental factors on allergic risk and compared the incidence of atopic conditions with a pre-pandemic Irish infant cohort, BASELINE. RESULTS: AD was more common in CORAL group at both 12 (26.5% vs. 15.5%; p < .001) and 24 months (21.3% vs. 15.9%; p = .02) compared with pre-pandemic BASELINE cohort. Within the CORAL group, those with AD at both 12- and 24-month appointments had a more severe AD phenotype associated with a higher risk of allergic sensitization. There was less milk (0% vs. 1%; p = .09), peanut (0.6% vs. 1.8%; p = .3), and egg allergy (0% vs. 2.9%; p < .001) in the CORAL group at 24 months compared with the BASELINE cohort. Aeroallergen sensitization increased between 12 and 24 months in the CORAL cohort (1.5% vs. 8.9%; p < .001), as did parent-reported wheezing episodes (9% vs. 24%; p < .001). CONCLUSIONS: Despite higher AD incidence in the CORAL cohort, the incidence of food sensitization and allergy are lower than expected pre-pandemic rates possibly reflecting the early introduction and maintenance of dietary allergens enhanced by changes in infant infections, antibiotic use, and breastfeeding in the first 2 years of life in the group. These beneficial effects of the lockdown could be outweighing the expected risk of less early-life microbial encounters outlined by the hygiene hypothesis.

Single low-dose exposure to cow's milk at diagnosis accelerates cow's milk allergic infants' progress on a milk ladder programme.

BACKGROUND: Cow's milk protein allergy (CMPA) is one of the most common food allergies in infancy. Most infants with CMPA tolerate baked milk from diagnosis and gradually acquire increased tolerance. Nevertheless, parents often display significant anxiety about this condition and a corresponding reluctance to progress with home introduction of dairy due to concerns about possible allergic reactions. OBJECTIVE: To evaluate the impact on gradual home introduction of foods containing cows' milk after a supervised, single low-dose exposure to whole milk at time of diagnosis. METHODS: Infants less than 12 months old referred with suspected IgE-mediated cow's milk allergy were recruited to an open-label randomized, controlled trial of intervention-a single dose of fresh cow's milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects-the ED05 - vs routine care. Both groups implemented graded exposure to CM (using the 12 step MAP Milk Tolerance Induction Ladder), at home. Parents completed food allergy quality of life questionnaires and State and Trait Anxiety Inventories (STAI). Main outcome measures were milk ladder position at 6 months and 12 months post-randomization. RESULTS: Sixty patients were recruited, 57 (95%) were followed to 6 months. By 6 months, 27/37 (73%) intervention subjects had reached step 6 or above on the milk ladder compared to 10/20 (50%) control subjects (p = .048). By 6 months, 11/37 (30%) intervention subjects had reached step 12 (i.e. drinking unheated cow's milk) compared to 2/20 (10%) of the controls (p = .049). Twelve months post-randomization, 31/36(86%) of the intervention group and 15/19(79%) of the control group were on step 6 or above. However, 24/37 (65%) of the intervention group were at step 12 compared to 7/20 (35%) of the control group (p = .03). Maternal STAIs were significantly associated with their infants' progress on the milk ladder and with changes in skin prick test and spIgE levels at 6 and 12 months. CONCLUSION: This study demonstrates the safety and effectiveness of introduction of baked milk implemented immediately after diagnosis of cows' milk allergy in a very young cohort. A supervised single dose of milk at the ED05  significantly accelerates this further, probably by giving parents the confidence to proceed. Maternal anxiety generally reflects infants' progress towards completion of the milk ladder, but pre-existing high levels of maternal anxiety are associated with poorer progress.

Ion chromatograph with three-dimensional printed absorbance detector for indirect ultraviolet absorbance detection of phosphate in effluent and natural waters.

An ion chromatography system employing a low-cost three-dimensional printed absorbance detector for indirect ultraviolet detection towards portable phosphate analysis of environmental and industrial waters has been developed. The optical detection cell was fabricated using stereolithography three-dimensional printing of nanocomposite material. Chromatographic analysis and detection of phosphate were carried out using a CS5A 4 × 250 mm analytical column with indirect ultraviolet detection using a 255 nm light-emitting diode. Isocratic elution using a 0.6 mM potassium phthalate eluent combined with 1.44 mM sodium bicarbonate was employed at a flow rate of 0.75 mL/min. A linear calibration range of 0.5 to 30 mg/L PO4 3- applicable to environmental and wastewater analysis was achieved. For retention time and peak area repeatability, relative standard deviation values were 0.68 and 4.09%, respectively. Environmental and wastewater samples were analyzed with the optimized ion chromatography platform and the results were compared to values obtained by an accredited ion chromatograph. For the analysis of environmental samples, relative errors of <14 % were achieved. Recovery analysis was also carried out on both freshwater and wastewater samples and recovery results were within the acceptable range for water analysis using standard ion chromatography methods.

Mass food challenges in a vacant COVID-19 stepdown facility: Exceptional opportunity provides a model for the future.

BACKGROUND: Internationally, the COVID-19 pandemic severely curtailed access to hospital facilities for those awaiting elective/semi-elective procedures. For allergic children in Ireland, already waiting up to 4 years for an elective oral food challenge (OFC), the restrictions signified indefinite delay. At the time of the initiative, there were approx 900 children on the Children's Health Ireland (CHI) waiting list. In July 2020, a project was facilitated by short-term (6 weeks) access to an empty COVID stepdown facility built, in a hotel conference centre, commandeered by the Health Service Executive (HSE), Ireland. The aim of this study was to achieve the rapid roll-out of an offsite OFC service, delivering high throughput of long waiting patients, while aligning with existing hospital policies and quality standards, international allergy guidelines and national social distancing standards. METHODS: The working group engaged key stakeholders to rapidly develop an offsite OFC facility. Consultant paediatric allergists, consultant paediatricians, trainees and allergy clinical nurse specialists were seconded from other duties. The facility was already equipped with hospital beds, bedside monitors (BP, pulse and oxygen saturation) and bedside oxygen. All medication and supplies had to be brought from the base hospital. Daily onsite consultant anaesthetic cover was resourced and a resuscitation room equipped. Standardized food challenge protocols were created. Access to the onsite hotel chef facilitated food preparation. A risk register was established. RESULTS: After 6 weeks of planning, the remote centre became operational on 7/9/2020, with the capacity of 27 OFC/day. 474 challenges were commenced: 465 (98%) were completed and 9 (2%) were inconclusive. 135 (29%) OFCs were positive, with 25 (5%) causing anaphylaxis. No child required advanced airway intervention. 8 children were transferred to the base hospital. The CHI allergy waiting list was reduced by almost 60% in only 24 days. CONCLUSIONS: Oral food challenges remain a vital tool in the care of allergic children, with their cost saving and quality-of-life benefits negatively affected by a delay in their delivery. This project has shown it is possible to have huge impacts on a waiting list efficiently, effectively and safely with good planning and staff buy-in-even in a pandemic. Adoption of new, flexible and efficient models of service delivery will be important for healthcare delivery in the post-COVID-19 era.

Long-term, open-label extension study of the efficacy and safety of epicutaneous immunotherapy for peanut allergy in children: PEOPLE 3-year results.

BACKGROUND: The PEPITES (Peanut EPIT Efficacy and Safety) trial, a 12-month randomized controlled study of children with peanut allergy and 4 to 11 years old, previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT) for peanut allergy (250 µg, daily epicutaneous peanut protein; DBV712 250 µg). OBJECTIVE: We sought to assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) PEOPLE (PEPITES Open-Label Extension) study. METHODS: Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250 µg, subjects who had received DBV712 250 µg in PEPITES underwent month-36 double-blind, placebo-controlled food challenge with an optional month-38 sustained unresponsiveness assessment. RESULTS: Of 213 eligible subjects who had received DBV712 250 µg in PEPITES, 198 (93%) entered PEOPLE, of whom 141 (71%) had assessable double-blind, placebo-controlled food challenge at month 36. At month 36, 51.8% of subjects (73 of 141) reached an eliciting dose of ≥1000 mg, compared with 40.4% (57 of 141) at month 12; 75.9% (107 of 141) demonstrated increased eliciting dose compared with baseline; and 13.5% (19 of 141) tolerated the full double-blind, placebo-controlled food challenge of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. Eighteen subjects underwent an optional sustained unresponsiveness assessment; 14 of those (77.8%) maintained an eliciting dose of ≥1000 mg at month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events were low (1%). CONCLUSIONS: These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen.

Googling Allergy in Ireland: Content Analysis.

BACKGROUND: Internet search engines are increasingly being utilized as the first port of call for medical information by the public. The prevalence of allergies in developed countries has risen steadily over time. There exists significant variability in the quality of health-related information available on the web. Inaccurately diagnosed and mismanaged allergic disease has major downstream effects on patients, general practitioners, and regional allergy services. OBJECTIVE: This study aimed to verify whether Ireland has a relatively high rate of web-based allergy-related searches, to establish the proportion of medically accurate web pages encountered by the public, and to compare current search results localized to Dublin, Ireland with urban centers elsewhere. METHODS: Google Trends was used to evaluate regional interest of allergy-related search terms over a 10-year period using terms "allergy," "allergy test," "food allergy," and "food intolerance." These terms were then inputted into Google search, localizing them to cities in Ireland, the United Kingdom, and the United States. Output for each search was reviewed by two independent clinicians and deemed rational or nonevidence based, as per current best practice guidelines. Searches localized to Dublin were initially completed in 2015 and repeated in 2019 to assess for changes in the quality of search results over time. RESULTS: Ireland has a persistently high demand for web-based information relating to allergy and ranks first worldwide for "allergy test," second for "food allergy" and "food intolerance," and seventh for "allergy" over the specified 10-year timeframe. Results for each of the four subsearches in Dublin (2015) showed that over 60% of websites promoted nonevidence-based diagnostics. A marginal improvement in scientifically robust information was seen in 2019, but results for "allergy test" and "food intolerance" continued to promote alternative testing 57% (8/14) of the time. This strongly contrasted with results localized to Southampton and Rochester, where academic and hospital-affiliated web pages predominantly featured. Government-funded Department of Health websites did not feature in the top five results for Dublin searches "allergy testing," "food allergy," or "food intolerance" in either 2015 or 2019. CONCLUSIONS: The Irish public demonstrates a keen interest in seeking allergy-related information on the web. The proportion of evidence-based websites encountered by the Irish public is considerably lower than that encountered by patients in other urban centers. Factors contributing to this are the lack of a specialist register for allergy in Ireland, inadequate funding for allergy centers currently in operation, and insufficient promotion by the health service of their web-based health database, which contains useful patient-oriented information on allergy. Increased funding of clinical allergology services will more meaningfully impact the health of patients if there is a parallel investment by the health service in information and communication technology consultancy to amplify their presence on the web.

Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion Among Children With Peanut Allergy: The PEPITES Randomized Clinical Trial.

Importance: There are currently no approved treatments for peanut allergy. Objective: To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic children. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled trial conducted at 31 sites in 5 countries between January 8, 2016, and August 18, 2017. Participants included peanut-allergic children (aged 4-11 years [n = 356] without a history of a severe anaphylactic reaction) developing objective symptoms during a double-blind, placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein. Interventions: Daily treatment with peanut patch containing either 250 µg of peanut protein (n = 238) or placebo (n = 118) for 12 months. Main Outcomes and Measures: The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose (highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed) determined by food challenges at baseline and month 12. Participants with baseline eliciting dose of 10 mg or less were responders if the posttreatment eliciting dose was 300 mg or more; participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. Adverse event evaluation included collection of treatment-emergent adverse events (TEAEs). Results: Among 356 participants randomized (median age, 7 years; 61.2% male), 89.9% completed the trial; the mean treatment adherence was 98.5%. The responder rate was 35.3% with peanut-patch treatment vs 13.6% with placebo (difference, 21.7% [95% CI, 12.4%-29.8%; P < .001]). The prespecified lower bound of the CI threshold was not met. TEAEs, primarily patch application site reactions, occurred in 95.4% and 89% of active and placebo groups, respectively. The all-causes rate of discontinuation was 10.5% in the peanut-patch group vs 9.3% in the placebo group. Conclusions and Relevance: Among peanut-allergic children aged 4 to 11 years, the percentage difference in responders at 12 months with the 250-µg peanut-patch therapy vs placebo was 21.7% and was statistically significant, but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result. The clinical relevance of not meeting this lower bound of the confidence interval with respect to the treatment of peanut-allergic children with epicutaneous immunotherapy remains to be determined. Trial Registration: ClinicalTrials.gov Identifier: NCT02636699.

Factors influencing accidental food allergic reactions in schools and preschools.

BACKGROUND: Children spend a large proportion of their childhood in schools. In Ireland, there is no government policy on the management of food allergy (FA) in schools or preschool childcare settings (CCS). There is limited data worldwide on rate of accidental allergic reactions (AARs) within these settings. AIM: The aim of this paper is to report the management of FA and the incidence of AARs in Irish school or preschool CCS. METHODS: A prospective observational study was established, enrolling children aged 2 to 16 years with confirmed FA. Participants were contacted at three monthly intervals for 1 year to report AARs to food. Data pertaining to schools and preschool CCS is reported here. RESULTS: A total of 521 children (402 attending school and 119 attending preschool CCS) were enrolled. The annualised incidence of AARs in school was 4.5% (95% CI 2.6-7.0) and in preschool CCS 5% (95% CI 1.8-11.1); 6 of 7 of the nut reactions occurred in schools banning nuts. Half (3/6) of the preschool reactions were to cow's milk; 174/521 (33%) children did not provide their individualised allergy action plan (AAP). Four out of 18 (22%) AARs in school were anaphylaxis and none were administered adrenaline by school staff. CONCLUSION: The incidence of AARs in this Irish cohort was found to be equivalent to the international experience. However, many of the recorded reactions identified in this study were likely avoidable. Preparation for AARs needs optimising. The ineffectiveness of "nut bans" remains unrecognised. Promoting milk and egg allergy resolution in infancy would likely reduce preschool- and school-based reaction numbers.

Foreign body granuloma secondary to ventriculo-peritoneal shunt: a rare scenario with a new insight.

Ventriculo-peritoneal shunts are used extensively for the management of hydrocephalus and frequently present with complications such as shunt blockage and infection. Cerebrospinal fluid (CSF) eosinophilia and allergic responses to the shunt itself are rare, poorly understood but increasingly recognised complications. Here, the authors describe a child who required multiple shunt revision surgeries due to extensive scalp tenderness overlying the shunt tubing and persistent severe headaches despite having a normal working shunt and no CSF infection or eosinophilia. Histological investigation of excised tissue during the last shunt revision demonstrated fibrosis with scar tissue and chronic inflammatory infiltrate with foreign body giant cells and few abortive granulomata. This was felt to represent a foreign body reaction to the shunt. A hypoallergenic 'extracted' shunt was trialled (extracted Delta® valve and extracted ventricular and peritoneal catheters; Medtronic) and the child has had no further shunt revisions and is currently asymptomatic 1 year after the insertion.