Updated Guidance Regarding The Risk ofAllergic Reactions to COVID-19 Vaccines and Recommended Evaluation and Management: A GRADE Assessment, and International Consensus Approach.

This guidance updates 2021 GRADE recomendations regarding immediate allergic reactions following COVID-19 vaccines and addresses re-vaccinating individuals with 1st dose allergic reactions and allergy testing to determine re-vaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 re-vaccination 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 recommenations. 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 UK, and the US formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy, and re-vaccination after a prior immediate allergic reaction. We suggest against >15-minute post-vaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest re-vaccination 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 pre-medication, split-dosing, or special precautions because of a comorbid allergic history.

Anaphylaxis: Revision of the Brighton collaboration case definition.

The Brighton Collaboration (BC) has formulated a number of case definitions which have primarily been applied to adverse events of special interest in the context of vaccine safety surveillance. This is a revision of the 2007 BC case definition for anaphylaxis. Recently, the BC definition has been widely used for evaluating reports of suspected anaphylaxis following COVID-19 vaccination. This has led to debate about the performance of the BC definition in comparison with those from the US National Institute of Allergy and Infectious Disease/Food Allergy Anaphylaxis Network (NIAID/FAAN) and the World Allergy Organization (WAO). BC convened an expert working group to revise the case definition based on their usual process of literature review and expert consensus. This manuscript presents the outcome of this process and proposes a revised case definition for anaphylaxis. Major and minor criteria have been re-evaluated with an emphasis on the reporting of observable clinical signs, rather than subjective symptoms, and a clearer approach to the ascertainment of levels of certainty is provided. The BC case definition has also been aligned with other contemporary and international case definitions for anaphylaxis.

Diagnostic accuracy of vaccine and vaccine excipient testing in the setting of allergic reactions to COVID-19 vaccines: A systematic review and meta-analysis.

For persons with immediate allergic reactions to mRNA COVID-19 vaccines, skin testing (ST) to the vaccine/excipients (polyethylene glycol[PEG] and polysorbate 80 [PS]) has been recommended, but has unknown accuracy. To assess vaccine/excipient ST accuracy in predicting all-severity immediate allergic reactions upon re-vaccination, systematic review was performed searching Medline, EMBASE, Web of Science, and the WHO global coronavirus database (inception-Oct 4, 2021) for studies addressing immediate (≤4 h post-vaccination) all-severity allergic reactions to 2nd mRNA COVID-19 vaccination in persons with 1st dose immediate allergic reactions. Cases evaluating delayed reactions, change of vaccine platform, or revaccination without vaccine/excipient ST were excluded. Meta-analysis of diagnostic testing accuracy was performed using Bayesian methods. The GRADE approach evaluated certainty of the evidence, and QUADAS-2 assessed risk of bias. Among 20 studies of mRNA COVID-19 first dose vaccine reactions, 317 individuals underwent 578 ST to any one or combination of vaccine, PEG, or PS, and were re-vaccinated with the same vaccine. Test sensitivity for either mRNA vaccine was 0.2 (95%CrI 0.01-0.52) and specificity 0.97 (95%CrI 0.9-1). PEG test sensitivity was 0.02 (95%CrI 0.00-0.07) and specificity 0.99 (95%CrI 0.96-1). PS test sensitivity was 0.03 (95%CrI 0.00-0.0.11) and specificity 0.97 (95%CrI 0.91-1). Combined for use of any of the 3 testing agents, sensitivity was 0.03 (95%CrI 0.00-0.08) and specificity was 0.98 (95%CrI 0.95-1.00). Certainty of evidence was moderate. ST has low sensitivity but high specificity in predicting all-severity repeat immediate allergic reactions to the same agent, among persons with 1st dose immediate allergic reactions to mRNA COVID-19 vaccines. mRNA COVID-19 vaccine or excipient ST has limited risk assessment utility.

Allergic diseases and immunodeficiencies in children, lessons learnt from COVID-19 pandemic by 2022: A statement from the EAACI-section on pediatrics.

By the April 12, 2022, the COVID-19 pandemic had resulted in over half a billion people being infected worldwide. There have been 6.1 million deaths directly due to the infection, but the pandemic has had many more short- and long-term pervasive effects on the physical and mental health of the population. Allergic diseases are among the most prevalent noncommunicable chronic diseases in the pediatric population, and health-care professionals and researchers were seeking answers since the beginning of pandemic. Children are at lower risk of developing severe COVID-19 or dying from infection. Allergic diseases are not associated with a higher COVID-19 severity and mortality, apart from severe/poorly controlled asthma. The pandemic disrupted routine health care, but many mitigation strategies, including but not limited to telemedicine, were successfully implemented to continue delivery of high-standard care. Although children faced a multitude of pandemic-related issues, allergic conditions were effectively treated remotely while reduction in air pollution and lack of contact with outdoor allergens resulted in improvement, particularly respiratory allergies. There is no evidence to recommend substantial changes to usual management modalities of allergic conditions in children, including allergen immunotherapy and use of biologicals. Allergic children are not at greater risk of multisystem inflammatory syndrome development, but some associations with Long COVID were reported, although the data are limited, and further research is needed. This statement of the EAACI Section on Pediatrics provides recommendations based on the lessons learnt from the pandemic, as available evidence.

Allergic diseases and immunodeficiencies in children, lessons learnt from COVID‐19 pandemic by 2022: A statement from the EAACI‐section on pediatrics

By the April 12, 2022, the COVID‐19 pandemic had resulted in over half a billion people being infected worldwide. There have been 6.1 million deaths directly due to the infection, but the pandemic has had many more short‐ and long‐term pervasive effects on the physical and mental health of the population. Allergic diseases are among the most prevalent noncommunicable chronic diseases in the pediatric population, and health‐care professionals and researchers were seeking answers since the beginning of pandemic. Children are at lower risk of developing severe COVID‐19 or dying from infection. Allergic diseases are not associated with a higher COVID‐19 severity and mortality, apart from severe/poorly controlled asthma. The pandemic disrupted routine health care, but many mitigation strategies, including but not limited to telemedicine, were successfully implemented to continue delivery of high‐standard care. Although children faced a multitude of pandemic‐related issues, allergic conditions were effectively treated remotely while reduction in air pollution and lack of contact with outdoor allergens resulted in improvement, particularly respiratory allergies. There is no evidence to recommend substantial changes to usual management modalities of allergic conditions in children, including allergen immunotherapy and use of biologicals. Allergic children are not at greater risk of multisystem inflammatory syndrome development, but some associations with Long COVID were reported, although the data are limited, and further research is needed. This statement of the EAACI Section on Pediatrics provides recommendations based on the lessons learnt from the pandemic, as available evidence.

COVID-19 and the importance of effective risk communication with children.

During the current COVID-19 pandemic, effective risk communication is essential to mitigate the mental health impact on children and their families. Effective risk communication involves being honest but yet reassuring, framing issues in an actionable way, and modeling realistically reassuring communication among adults. Health care providers may discuss with families principles of modeling good media consumption habits to mitigate misinformation on social media. In addition, health numeracy and health literacy need to be integrated into proper risk communication.

The Role of Access and Cost-Effectiveness in Managing Asthma: A Systematic Review.

BACKGROUND: Inconsistent and unequal access to medical care is an issue that predates the COVID19 pandemic, which only worsened the problem. Limited access to care from asthma specialists and other specialists treating comorbid diseases may adversely affect asthma. OBJECTIVE: The purpose of this review is to identify health disparities associated with access to care for asthma, and cost-effectiveness of therapies and interventions addressing this health disparity. METHODS: A narrative systematic review was undertaken using MeSH searches of English language articles published in CINAHL, Scopus, or PubMed. RESULTS: A total of 725 articles were identified. Barriers recognized from the literature included access to diagnostic spirometry, access to specialists, medication formulary restrictions, and issues leading to medical nonadherence. Telemedicine, school-based health care interventions, digital applications, and non-office-based digital spirometry could be used to address these gaps in access to asthma care while potentially being cost-effective. CONCLUSION: With the widespread adoption of telemedicine because of the pandemic, and adoption of other mobile services, we now have potential tools that can increase access to asthma care, which can help address this health care inequity. Evidence is limited, but favorable, that some of these tools may be cost-effective.

Risk of Second Allergic Reaction to SARS-CoV-2 Vaccines: A Systematic Review and Meta-analysis.

IMPORTANCE: Vaccination against SARS-CoV-2 is a highly effective strategy to prevent infection and severe COVID-19 outcomes. The best strategy for a second dose of vaccine among persons who had an immediate allergic reaction to their first SARS CoV-2 vaccination is unclear. OBJECTIVE: To assess the risk of severe immediate allergic reactions (eg, anaphylaxis) to a second dose of SARS-CoV-2 mRNA vaccine among persons with immediate allergic reactions to their first vaccine dose. DATA SOURCES: MEDLINE, Embase, Web of Science, and the World Health Organization Global Coronavirus database were searched from inception through October 4, 2021. STUDY SELECTION: Included studies addressed immediate allergic reactions of any severity to a second SARS-CoV-2 vaccine dose in persons with a known or suspected immediate allergic reaction (<4 hours after vaccination) after their first SARS-CoV-2 vaccine dose. Studies describing a second vaccine dose among persons reporting delayed reactions (>4 hours after vaccination) were excluded. DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently selected studies, extracted data, and assessed risk of bias. Random-effects models were used for meta-analysis. The GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach evaluated certainty of the evidence. MAIN OUTCOMES AND MEASURES: Risk of severe immediate allergic reaction and repeated severe immediate allergic reactions with a second vaccine dose. Reaction severity was defined by the reporting investigator, using Brighton Collaboration Criteria, Ring and Messmer criteria, World Allergy Organization criteria, or National Institute of Allergy and Infectious Diseases criteria. RESULTS: Among 22 studies of SARS-CoV-2 mRNA vaccines, 1366 individuals (87.8% women; mean age, 46.1 years) had immediate allergic reactions to their first vaccination. Analysis using the pooled random-effects model found that 6 patients developed severe immediate allergic reactions after their second vaccination (absolute risk, 0.16% [95% CI, 0.01%-2.94%]), 232 developed mild symptoms (13.65% [95% CI, 7.76%-22.9%]), and, conversely, 1360 tolerated the dose (99.84% [95% CI, 97.09%-99.99%]). Among 78 persons with severe immediate allergic reactions to their first SARS-CoV-2 mRNA vaccination, 4 people (4.94% [95% CI, 0.93%-22.28%]) had a second severe immediate reaction, and 15 had nonsevere symptoms (9.54% [95% CI, 2.18%-33.34%]). There were no deaths. Graded vaccine dosing, skin testing, and premedication as risk-stratification strategies did not alter the findings. Certainty of evidence was moderate for those with any allergic reaction to the first dose and low for those with severe allergic reactions to the first dose. CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of case studies and case reports, the risk of immediate allergic reactions and severe immediate reactions or anaphylaxis associated with a second dose of an SARS-CoV-2 mRNA vaccine was low among persons who experienced an immediate allergic reaction to their first dose. These findings suggest that revaccination of individuals with an immediate allergic reaction to a first SARS-CoV-2 mRNA vaccine dose in a supervised setting equipped to manage severe allergic reactions can be safe.

Risk factors for post-COVID-19 condition in previously hospitalised children using the ISARIC Global follow-up protocol: a prospective cohort study.

BACKGROUND: The long-term sequelae of coronavirus disease 2019 (COVID-19) in children remain poorly characterised. This study aimed to assess long-term outcomes in children previously hospitalised with COVID-19 and associated risk factors. METHODS: This is a prospective cohort study of children (≤18 years old) admitted to hospital with confirmed COVID-19. Children admitted between 2 April 2020 and 26 August 2020 were included. Telephone interviews used the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 Health and Wellbeing Follow-up Survey for Children. Persistent symptoms (>5 months) were further categorised by system(s) involved. RESULTS: 518 out of 853 (61%) eligible children were available for the follow-up assessment and included in the study. Median (interquartile range (IQR)) age was 10.4 (3-15.2) years and 270 (52.1%) were girls. Median (IQR) follow-up since hospital discharge was 256 (223-271) days. At the time of the follow-up interview 126 (24.3%) participants reported persistent symptoms, among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%) and sensory problems (29, 5.6%) were the most common. Multiple symptoms were experienced by 44 (8.4%) participants. Risk factors for persistent symptoms were: older age "6-11 years" (OR 2.74, 95% CI 1.37-5.75) and "12-18 years" (OR 2.68, 95% CI 1.41-5.4), and a history of allergic diseases (OR 1.67, 95% CI 1.04-2.67). CONCLUSIONS: A quarter of children experienced persistent symptoms months after hospitalisation with acute COVID-19 infection, with almost one in 10 experiencing multisystem involvement. Older age and allergic diseases were associated with higher risk of persistent symptoms at follow-up.

The Revenge of Unintended Consequences of Anaphylaxis-Risk Overdiagnosis: How Far We Have Come and How Far We Have to Go.

Overdiagnosis of anaphylaxis risk is an underappreciated aspect of anaphylaxis prevention. Whereas the benefits of anaphylaxis-risk prevention are well known, potential harms resulting from preemptive approaches to mitigate anaphylaxis-risk are not insignificant. Still, great progress has been made in recent years to avoid the unintended consequences of anaphylaxis-risk overdiagnosis. Reflection on recent advances in the use of diagnostic testing, as well as the application of diagnostic labels, provides an important perspective to understand how far the specialty of allergy and immunology has come in improving the lives of patients and families. Examples of recent paradigm shifts in anaphylaxis-risk management include approaches to peanut allergy prevention without screening, deferral of corticosteroids to prevent biphasic anaphylaxis reactions, reevaluation of reflex use of emergency medical services for resolved community anaphylaxis, and an approach to penicillin allergy delabeling with direct oral challenge. Routine medical practices to decrease anaphylaxis risk can have lifelong impacts for patients-beyond just preventing anaphylaxis. As our understanding of these trade-offs evolves, it becomes necessary to weigh both the benefits and the harms of past management approaches. Because medicine remains a science of uncertainty and an art of probability, a critical approach to risk mitigation remains necessary to find the often-elusive balance in anaphylaxis prevention.

The COVID-19 pandemic: Adverse effects on the social determinants of health in children and families.

OBJECTIVE: To describe the impact of social determinants on the experience of the coronavirus disease 2019 (COVID-19) pandemic within the pediatric population, how this impact may influence the long-term health and security of children, and what measures can be taken to ameliorate this impact moving forward. DATA SOURCES: Nonsystematic review of relevant literature and news sources. STUDY SELECTIONS: Relevant literature and news sources. RESULTS: There have been increases in housing insecurity and food insecurity during the pandemic, including global increases in poverty. Public policies such as school closures have had a disproportionate impact on those facing adverse social determinants. There has been a dramatic increase in reports of abuse-related injuries and other injuries indicative of child abuse during the pandemic. In addition, there are disproportionate impacts of COVID-19 based on race and ethnicity within the United States. It is clear that children are facing more adverse determinants as a result of this pandemic and that there are both short-term and long-term implications associated. For those living in poverty or with other adverse social determinants of health, the pandemic has made a bad situation worse. Ongoing studies are required to measure the impact of COVID-19 on those with adverse social determinants, in particular among children. CONCLUSION: Social determinants of health must be part of pandemic research priorities, public health and vaccination goals, and economic policy implementation. The impact of the COVID-19 pandemic has further served to shed a light on the broad disparities that exist within our society and their direct and indirect impacts on health outcomes.