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.

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.

Hydrolyzed Formula for Every Infant?

Presently, hydrolyzed formulas (HF) are used primarily in infants that cannot be exclusively breastfed, those with cow's milk allergy and for primary prevention of allergic disease, but HFs are increasingly being used worldwide, begging the question if they may be recommended as the optimal choice for all standard-risk, full-term, non-exclusively breastfed infants. Data regarding the nutritional adequacy of modern-day HFs are scarce and lack long-term data suggesting that growth in infants fed HF versus an intact protein formula (IPF) is different. While human breast milk is the optimal source of nutrition for multiple reasons, a 2006 systematic review determined there were no comparable long-term studies regarding prolonged use of HFs versus breastfeeding. Meta-analyses of formula consumption and risk of atopic dermatitis (AD) have found that infants fed partially HF compared to IPF had a lower risk of AD, but there are significant limitations to these studies, making conclusions about the general use of HFs problematic. Costs should be considered in decision-making regarding the choice of the formula, but global comparison of this is difficult given large cost differences in different countries. Despite the issues raised here, the desire to provide concrete recommendations of widespread HF use needs to be balanced carefully in order not to overstate claims of benefit. Long-term studies are needed to investigate the feasibility of HF as a routine feeding option for healthy, standard-risk infants. Because of the paucity of data, routine use of HF as an equivalent option to breastfeeding or IPF cannot be supported at present based on available scientific evidence.