First-Dose mRNA COVID-19 Vaccine Allergic Reactions: Limited Role for Excipient Skin Testing.

The Centers for Disease Control and Prevention state that a severe or immediate allergic reaction to the first dose of an mRNA COVID-19 vaccine is a contraindication for the second dose. To assess outcomes associated with excipient skin testing after a reported allergic reaction to the first dose of mRNA COVID-19 vaccine. We identified a consecutive sample of patients with reported allergic reactions after the first dose of mRNA COVID-19 vaccine who underwent allergy assessment with skin testing to polyethylene glycol (PEG) and, when appropriate, polysorbate 80. Skin testing results in conjunction with clinical phenotyping of the first-dose mRNA COVID-19 vaccine reaction guided second-dose vaccination recommendation. Second-dose mRNA COVID-19 vaccine reactions were assessed. Eighty patients with reported first-dose mRNA COVID-19 vaccine allergic reactions (n = 65; 81% immediate onset) underwent excipient skin testing. Of those, 14 (18%) had positive skin tests to PEG (n = 5) and/or polysorbate 80 (n = 12). Skin testing result did not affect tolerance of the second dose in patients with immediate or delayed reactions. Of the 70 patients who received the second mRNA COVID-19 vaccine dose (88%), 62 had either no reaction or a mild reaction managed with antihistamines (89%), but 2 patients required epinephrine treatment. Three patients with positive PEG-3350 intradermal (methylprednisolone) testing tolerated second-dose mRNA COVID-19 vaccination. Refresh Tears caused nonspecific skin irritation. Most individuals with a reported allergic reaction to the first dose of mRNA COVID-19 vaccines, regardless of skin test result, received the second dose safely. More data are needed on the value of skin prick testing to PEG (MiraLAX) in evaluating patients with mRNA COVID-19 vaccine anaphylaxis. Refresh Tears should not be used for skin testing.

Wolfson AR ，Robinson LB ，Li L ，McMahon AE ，Cogan AS ，Fu X ，Wickner P ，Samarakoon U ，Saff RR ，Blumenthal KG ，Banerji A ... -  《-》

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.

Greenhawt M ，Abrams EM ，Shaker M ，Chu DK ，Khan D ，Akin C ，Alqurashi W ，Arkwright P ，Baldwin JL ，Ben-Shoshan M ，Bernstein J ，Bingemann T ，Blumchen K ，Byrne A ，Bognanni A ，Campbell D ，Campbell R ，Chagla Z ，Chan ES ，Chan J ，Comberiati P ，Dribin TE ，Ellis AK ，Fleischer DM ，Fox A ，Frischmeyer-Guerrerio PA ，Gagnon R ，Grayson MH ，Horner CC ，Hourihane J ，Katelaris CH ，Kim H ，Kelso JM ，Lang D ，Ledford D ，Levin M ，Lieberman J ，Loh R ，Mack D ，Mazer B ，Mosnaim G ，Munblit D ，Mustafa SS ，Nanda A ，Oppenheimer J ，Perrett KP ，Ramsey A ，Rank M ，Robertson K ，Sheikh J ，Spergel JM ，Stukus D ，Tang MLK ，Tracy JM ，Turner PJ ，Whalen-Browne A ，Wallace D ，Wang J ，Waserman S ，Witry JK ，Worm M ，Vander Leek TK ，Golden DBK ... -  《-》

The Polysorbate containing AstraZeneca COVID-19 vaccine is tolerated by polyethylene glycol (PEG) allergic patients.

Polyethylene glycol (PEG) is the excipient found in the mRNA COVID-19 vaccines. We previously demonstrated PEG allergy was a cause of severe anaphylaxis to the Pfizer/BioNTech COVID-19 vaccine. PEG is widely used in many household products, cosmetics and medicines. However PEG allergy is rare, there have been few confirmed cases of PEG allergy. The excipient of potential concern in the AstraZeneca COVID-19 vaccine is polysorbate 80 (PS80). Cross-reactivity between PEG and polysorbate has been suggested, based on their composition and skin-test data. The aim of this study was to determine whether PEG-allergic patients could be vaccinated with the PS80 containing AstraZeneca COVID-19 vaccine. Eight patients with PEG allergy were identified by the allergy clinic at Cambridge University Hospital. Patients underwent skin prick testing to PS80 (20%) and to the AstraZeneca COVID-19 vaccine prior to vaccination. All eight patients allergic to PEG tolerated the AstraZeneca COVID-19 vaccine, even in 2 patients where the PS80 skin prick test was positive and 1 with a positive skin prick test to the AstraZeneca COVID-19 vaccine. Patients allergic to PEG, previously denied COVID vaccination, may now be safely vaccinated with the PS80 containing AstraZeneca vaccine and need only avoid the PEG-containing mRNA COVID-19 vaccines. This opens up the possibility that these patients will also tolerate other vaccines containing PS80 such as the Janssen/Johnson and Johnson COVID-19 vaccine. Clinical cross-reactivity between PEG and PS80 did not occur in this vaccine setting.

Sellaturay P ，Gurugama P ，Harper V ，Dymond T ，Ewan P ，Nasser S ... -  《-》

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

Chu DK ，Abrams EM ，Golden DBK ，Blumenthal KG ，Wolfson AR ，Stone CA Jr ，Krantz MS ，Shaker M ，Greenhawt M ... -  《-》

COVID vaccination can be performed in patients with a history of allergic reactions to the vaccines or their components: experience from a specialist clinic in South Australia.

The development of vaccines against SARS-CoV2 has been a key public health response to the COVID-19 pandemic. However, since their introduction, there have been reports of anaphylactic reactions to vaccines in individuals with history of allergic reactions to other vaccines, excipients or to COVID vaccines. A dedicated adult COVID vaccine allergy clinic with a standardised allergy testing protocol was set up to investigate safety and suitability of available COVID vaccines in Australia. Patients referred to a state-wide COVID-19 vaccine allergy clinic between March and August 2021 with a history of allergy underwent skin-prick testing and intradermal testing to both available vaccine formulations (BNT162b2 and ChAdOx1-S), excipients (polyethylene glycol and polysorbate 80), excipient-containing medications and controls. Basophil activation testing was conducted in few subjects with convincing history of immediate type reactions. Fifty-three patients underwent testing for possible excipient allergy (n = 19), previous non-COVID vaccine reaction (n = 13) or previous reaction to dose 1 of COVID-19 vaccine (n = 21). Patients were predominantly female (n = 43, 81%), aged 18-83 (median 54) years. Forty-four patients tested negative and 42 of these received at least their first dose of a COVID-19 vaccine. Nine patients tested positive to excipients or excipient-containing medication only (n = 3), or vaccines (n = 6). Five patients were positive to just BNT162b2, 3/5 have been vaccinated with ChAdOx1-S. One who was skin test positive to both vaccines, but negative BAT to ChAdOx1-S was successfully vaccinated with ChAdOx1-S. Even in a high-risk population, most patients can be vaccinated with available COVID-19 vaccines. This paper reports local experiences using a combined allergy testing protocol with skin testing and BAT during the pandemic.

Tunbridge M ，Perkins G ，Lee M ，Salehi T ，Ryoo D ，Kette F ，Smith W ，Gold M ，Le TA ，Yuson C ，Hissaria P ... -  《-》