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.

Comparison of Standard, Cluster, and Rush Allergy Immunotherapy Buildup Protocols.

BACKGROUND: Allergy immunotherapy (AIT) involves a dose-escalation phase following 1 of 3 protocols: standard, cluster, or rush. Although the cluster and rush protocols have been shown to decrease the time to reach maintenance dosing, there is a lack of direct comparison between the protocols. OBJECTIVE: This study aimed to evaluate the differences in time to maintenance dosing and occurrence of adverse reactions among the dose-escalation protocols. METHODS: A retrospective observation study of patients on AIT was conducted. Patients were categorized as participating in the standard, cluster, or rush buildup protocols. Patients on the rush protocol, unlike the standard and cluster protocols, were required to receive prednisone, montelukast, cetirizine, and famotidine on the rush day and first 2 weekly injections thereafter. Variables analyzed include patient demographics, time until maintenance dosing, rate of adverse reactions, treatments required for reactions, and AIT formulation. RESULTS: Data were reviewed on 237 patients on the standard (n = 41), cluster (n = 122), and rush (n = 74) protocols. The maintenance dose was achieved faster with the rush (16.50 weeks) and cluster (19.33 weeks) buildup protocols than the standard (31.09 weeks) protocol (P < .001). There was no statistically significant difference between time to maintenance dosing when comparing the cluster and rush protocols (P = .322). Despite pretreatment with the rush protocol, the rate of systemic reactions was the same for the standard (9.76%), cluster (9.84%), or rush (14.86%) buildup protocols (P = .526). CONCLUSION: Patients on the cluster buildup protocol for AIT achieved maintenance dosing in a comparable time frame as the rush protocol with a similar rate of systemic reactions and without the need for the pretreatment required with rush immunotherapy.

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.

The adverse reactions to vaccines practice parameter 10 years on-what have we learned?

OBJECTIVE: To provide updated information on the evaluation and management of adverse reactions to vaccines. DATA SOURCES: PubMed (MEDLINE) search since publication of a practice parameter in 2012. STUDY SELECTIONS: Original articles and guidelines on adverse reactions to vaccines, including vaccines against severe acute respiratory syndrome coronavirus 2 or coronavirus disease 2019 (COVID-19). RESULTS: Current guidelines conclude that patients with egg allergy are not at increased risk for reaction to egg-based influenza vaccines. Except for gelatin, most patients with allergy to vaccine constituents tolerate vaccines containing them. Most patients who have immediate reactions after receiving COVID-19 vaccines go on to receive a subsequent dose uneventfully. CONCLUSION: The risk of reactions to vaccination should be weighed against the risk of having a vaccine-preventable disease if the vaccine is withheld. There is no need to ask about egg allergy before the administration of influenza vaccines, including on screening forms. In most cases, an allergy to a vaccine constituent is not a contraindication to the vaccine containing it. Patients who have had possible anaphylactic reactions to vaccines should be evaluated by an allergist rather than simply being labeled allergic, because most can go on to receive subsequent doses. Most immediate reactions to COVID-19 vaccines are not allergic, and care should be taken to not label such reactions as anaphylactic. The role, if any, of polyethylene glycol in these reactions has yet to be revealed.

The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach.

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.

Sensorineural hearing loss (SNHL) as an adverse event following immunization (AEFI): Case definition & guidelines for data collection, analysis, and presentation of immunization safety data.

This is a Brighton Collaboration case definition of the term "Sensorineural Hearing Loss" to be utilized in the evaluation of adverse events following immunization. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for Lassa Fever and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and define levels of diagnostic certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network.

Unproven Diagnostic Tests for Adverse Reactions to Foods.

Patients often seek opinions from allergists regarding unconventional testing for adverse reactions to foods. These tests include flow cytometry to measure the change in white blood cell volumes after incubation with foods, measurement of serum IgG or IgG4 antibodies directed against foods, intradermal provocation-neutralization with food allergens, hair analysis, electrodermal testing, and applied kinesiology. In some cases, although the laboratory methods may be valid, there are no studies showing correlation with disease. In other cases, blinded, controlled studies have shown a lack of reproducibility and a lack of correlation with disease. Most of the tests lack biologic plausibility. By understanding the methodology of these tests and the lack of evidence supporting their utility, allergists can provide knowledgeable, evidence-based information to patients who inquire about them.