Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination.

BACKGROUND: The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms. METHODS: Selected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020-March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination ("controls") were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay (DCBA). Anti-PEG IgG and IgM were measured using two different assays: DCBA and a PEGylated-polystyrene bead assay. Laboratorians were blinded to case/control status. RESULTS: All 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65 %) were hospitalized and 7 (35 %) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10 %) case-patients vs 8 of 30 (27 %) controls (p = 0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0 %) vs 1 of 30 (3 %) controls (p >n 0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats. CONCLUSION: Our results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination.

Evaluation of pediatric patients with suspected polyethylene glycol and polysorbate allergy before mRNA SARS-CoV2 vaccination.

mRNA vaccines, particularly, have been associated with an increased risk of allergic reactions and rarely anaphylaxis. Although rare, vaccine reactions can cause significant anxiety and fear in the population, leading to indecision and vaccine refusal. This study aimed to retrospectively evaluate the role of polyethylene glycol (PEG) sensitivity in vaccination decision-making in pediatric patients at high risk of allergy or with suspected allergic reactions to the first dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine. Seventeen enrolled patients were found to have decreased readiness to receive the Coronavirus Disease 2019 (COVID-19) vaccine after developing hypersensitivity to multiple and/or injectable drugs. Skin testing was performed. A basophil activation test with PEG-2000 and 4000 was performed on three patients who were ineligible for skin prick tests. Nine patients with negative tests received the vaccine without complications. One patient had urticarial angioedema despite negative tests. Three patients with positive tests did not agree to desensitization with the mRNA vaccine, and one of them was vaccinated with the inactivated COVID-19 vaccine. Four patients recurred despite negative tests. The general recommendation for patients describing severe reactions to drugs, foods, and allergens, such as toxins that do not contain the adjuvants of the SARS-CoV-2 vaccines, is to be routinely vaccinated with safety precautions. Excipients such as PEG and polysorbate-80 used in COVID-19 vaccines could be potential allergens, but this hypothesis is unclear. The predictive values of these adjuvants for skin testing and in vitro testing are controversial. Further research is needed on the hypersensitivity reactions of adjuvants, the predictive values of skin tests, and etiopathogenesis.

Identifying and Managing Those at Risk for Vaccine-Related Allergy and Anaphylaxis.

Immediate hypersensitivity reactions to vaccines, the most severe of which is anaphylaxis, are uncommon events occurring in fewer than 1 in a million doses administered. These reactions are infrequently immunoglobulin E-mediated. Because they are unlikely to recur, a reaction to a single dose of a vaccine is rarely a contraindication to redosing. This narrative review article contextualizes the recent knowledge we have gained from the coronavirus 2019 (COVID-19) pandemic rollout of the new mRNA platform with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines within the much broader context of what is known about immediate reactions to other vaccinations of routine and global importance. We focus on what is known about evidence-based approaches to diagnosis and management and what is new in our understanding of mechanisms of immediate vaccine reactions. Specifically, we review the epidemiology of immediate hypersensitivity vaccine reactions, differential diagnosis for immune-mediated and nonimmune reaction clinical phenotypes, including how to recognize immunization stress-related responses. In addition, we highlight what is known about mechanisms and review the rare but important contribution of excipient allergies and specifically when to consider testing for them as well as other key features that contribute to safe evaluation and management.

[Allergy to Pfizer-BioNTech® vaccine demonstrated by skin testing]. / Alergia a la vacuna Pfizer-BioNTech® demostrada mediante pruebas cutáneas.

BACKGROUND: The Pfizer-BioNTech® BNT162b2 vaccine, provides 95% effectiveness from the second dose onwards. The reported rate of anaphylaxis to COVID-19 vaccines is 4.7 cases/million doses administered. CASE REPORT: 30-year-old female, health professional, history of allergic rhinitis, asthma, reaction to eye cosmetics and adhesive tape: erythema, edema, and local pruritus. Immediately after application of the first dose of Pfizer-BioNTech vaccine, she presented grade III anaphylaxis. The patient was stratified, phenotyped and skin tests with PEG 3350 were positive. A recommendation was issued not to reapply vaccine containing polyethylene glycol and alternatives were offered. CONCLUSIONS: An adequate risk stratification should be performed before applying mRNA-based COVID-19 vaccines for the first time in at-risk groups. In case of anaphylaxis at the first dose, phenotyping and further study with PEG skin tests should be performed and vaccination alternatives should be offered.

INTRODUCCIÓN: La vacuna Pfizer-BioNTech® BNT162b2 proporciona efectividad del 95% a partir de la segunda dosis. La tasa de anafilaxia reportada de vacunas para COVID-19 es de 4.7 casos por millón de dosis administradas. REPORTE DEL CASO: Paciente femenina de 30 años, profesional de la salud, con antecedentes de rinitis alérgica, asma, reacción a productos cosméticos en los párpados y al pegamento de la cinta adhesiva (eritema, edema y prurito local). Posterior a la aplicación de la primera dosis de la vacuna Pfizer-BioNTechÒ tuvo un evento de anafilaxia grado III. Se estratificó, fenotipificó y efectuaron pruebas cutáneas con PEG-3350, que resultaron positivas. Se sugirió no aplicar la aplicar vacuna de refuerzo que contuviera polietilenglicol y se ofrecieron alternativas de tratamiento. CONCLUSIONES: Es importante efectuar la adecuada estratificación de riesgo antes de aplicar las vacunas para COVID-19 basadas en ARNm por primera vez. En caso de anafilaxia es necesario fenotipificar y ampliar el estudio con pruebas cutáneas con PEG, además de otorgar alternativas de vacunación.

Adverse event reports of anaphylaxis after Comirnaty and Vaxzevria COVID-19 vaccinations, Western Australia, 22 February to 30 June 2021.

Within the first 4 months of the Western Australian COVID-19 immunisation programme, 49 suspected anaphylaxis cases were reported to the vaccine safety surveillance system. Twelve reports met Brighton Collaboration case definition, corresponding to rates of 15.9 and 17.7 per million doses of Vaxzevria and Comirnaty administered respectively.

Case Report: Anaphylactoid Shock Associated with Snakebite Envenoming in Portugal.

Although rare in Portugal, snakebite envenoming entails severe morbidity and mortality. We present the case of a 65-year-old woman bitten on her leg in a northern coastal region in Portugal, on a walk during the COVID-19 pandemic lockdown. Despite first looking for help at the nearest pharmacy, she developed anaphylactoid shock and was promptly driven to a tertiary hospital, where antivenom was administered in a timely manner under close monitoring. Prophylactic antibiotics were started and maintained based on elevated inflammatory markers and signs of wound inflammation. She evolved favorably, with rapid weaning of vasopressors and resolution of end-organ dysfunction. This case highlights the importance of prompt recognition and describes crucial steps in envenomation management in a country where snakebite is infrequent, but potentially fatal.

An update on anaphylaxis and urticaria.

Notable scientific developments have taken place in the field of anaphylaxis and urticaria in recent years; they are highlighted in this review. Case-control studies, genome-wide association studies, and large omics analyses have promoted further insights into not only the underlying genetics but also the biomarkers of both anaphylaxis and urticaria. New evidence regarding IgE-dependent and non-IgE-dependent mechanisms of anaphylaxis and urticaria, including the Mas-related G protein-coupled receptor (MRGPR [formerly MRG]) signaling pathway, has been gained. Putative elicitors of anaphylactic reactions in the context of coronavirus disease 2019 (COVID-19) vaccination and impact of the COVID-19 pandemic on the management and course of chronic urticaria have been reported. Clinical progress has also been made regarding the severity grading and risk factors of anaphylaxis, as well as the distinction of phenotypes and elicitors of both diseases. Furthermore, novel treatment approaches for anaphylaxis and subtypes of urticaria have been assessed, with different outcome and potential for a better disease control or prevention.

[Polyethylengylcole - Friend or Foe?] / Polyethylenglycol ­ Freund oder Feind?

Anaphylactic reactions following vaccination are rare. However, anaphylactic reactions towards the Pfizer-BioNTech Covid-19 vaccine were first reported in two patients in the UK and another 19 in the USA. Pegylation with polyethylene glycol (PEG) was thought to be the possible culprit. Pegylation is a common process in the manufacture of vaccines in order to prevent early degradation by the immune system. PEG is a polyether like e. g. Laureth-9, polidocanol, thesit and macrogol and is found in foodstuffs, cosmetics and personal care products as well as in liposomes and nanoparticles, as drug-delivery-system and as osmotic laxans for gastroscopies/coloscopies. Given the widespread use of PEG, reactions to vaccinations are rare and therefore no reason to exclude allergic patients in principle or indeed those who know the exact cause of a former anaphylaxis. In Germany, medical doctors are obliged to report any severe adverse reactions following vaccination; it is hoped that this procedure will help to resolve any remaining questions.

Anaphylaxis in elderly people.

PURPOSE OF REVIEW: Anaphylaxis is common in old-age adults but is insufficiently understood by physicians, and may be underdiagnosed. This review discusses the specificities of anaphylaxis in this age group and stresses the importance of adrenaline in its management. RECENT FINDINGS: Data from the European Anaphylaxis Registry on elderly patients is a major finding. Other findings include the prevention of possible anaphylactic reactions in coronavirus disease 2019 vaccination as well as some new epidemiologic data. SUMMARY: The most common risk factors are hymenoptera venom and food and drug allergy. Cardiovascular symptoms are the most important ones to reverse in old-age adults, especially due to the multiple comorbidities. Anaphylaxis in old-age adults has a more severe outcome than in younger ones. Polypharmacy is a specific factor to be considered. The Airway, Breathing, Circulation, Disability, Exposure (ABCDE) algorithm is applicable in all clinical emergencies for immediate assessment and treatment, and should be considered for all patients. Adrenaline is the mainstay of the management of the condition. There are no absolute contraindications to the prescription of self-injectable adrenaline in elderly individuals at risk of anaphylaxis.

[Path of a fighter]. / La désensibilisation allergénique au secours de la récidive.

Allergy is a frequent and often disabling condition for the patients. In the context of allergic rhinitis and asthma or anaphylactic shock to hymenoptera venom, allergenic desensitization can be proposed to limit the symptoms or recurrence of major reactions. Access to this treatment is made difficult by a lack of allergists, a lack of products or, more recently, by the Covid-19 crisis.

Near real-time surveillance of safety outcomes in US COVID-19 vaccine recipients aged 12 to 64 years.

BACKGROUND: Active monitoring of safety outcomes following COVID-19 vaccination is critical to understand vaccine safety and can provide early detection of rare outcomes not identified in pre-licensure trials. We present findings from an early warning rapid surveillance system in three large commercial insurance databases including more than 16 million vaccinated individuals. METHODS: We evaluated 17 outcomes of interest following COVID-19 vaccination among individuals aged 12-64 years in Optum, HealthCore, and CVS Health databases from December 11, 2020, through January 22, 2022, January 7, 2022, and December 31, 2021, respectively. We conducted biweekly or monthly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination. FINDINGS: Among 17 outcomes evaluated, 15 did not meet the threshold for statistical signal in any of the three databases. Myocarditis/pericarditis met the statistical threshold for a signal following BNT162b2 in two of three databases (RRs: 1.83-2.47). Anaphylaxis met the statistical threshold for a signal in all three databases following BNT162b2 vaccination (RRs: 4.48-10.86) and mRNA-1273 vaccination (RRs: 7.64-12.40). DISCUSSION: Consistent with published literature, our near-real time monitoring of 17 adverse outcomes following COVID-19 vaccinations identified signals for myocarditis/pericarditis and anaphylaxis following mRNA COVID-19 vaccinations. The method is intended for early detection of safety signals, and results do not imply a causal effect. Results of this study should be interpreted in the context of the method's utility and limitations, and the validity of detected signals must be evaluated in fully adjusted epidemiologic studies.

Cat allergy in children and the effect of the COVID-19 pandemic.

Background: Cat allergen is among the most common household allergens and can cause respiratory allergies and anaphylaxis in children. Objective: The aim of this study was to evaluate the characteristics of cat allergies in children and the impact of the coronavirus disease 2019 (COVID-19) pandemic on these characteristics. Methods: The study included pediatric patients with cat allergen sensitization demonstrated by skin-prick test (SPT) over a period of 2 years: 1 year before and 1 year during the pandemic. Demographic data, clinical features, and laboratory findings were evaluated from the patients' records. Results: Of 7428 SPTs performed, 566 patients (7.6%) were sensitized to cat allergen (56% boys; median age, 11 years). Fifty-eight percent of the patients (n = 329) presented during the pandemic period, 44.5% (n = 252) had symptoms with cat exposure, and 9% (n = 51/566) had anaphylaxis. Allergic rhinitis and asthma were present in 76% (n = 431) and 46.6% (n = 264) of the patients, respectively. When compared to prepandemic period, patients who presented during the pandemic had higher rates of cat sensitization (15% in pandemic group versus 4.4% in prepandemic group of all SPTs performed; p < 0.05), cat ownership (29.1% versus 13.9%; p < 0.001), and symptoms on cat exposure (51% versus 34%; p < 0.001). Factors that predicted symptom development in the patients who were cat sensitized were induration > 5 mm on SPT (odds ratio [OR] 1.9 [95% confidence interval {95% CI}], 1.1-3.2), cat ownership (OR 9.2 [95% CI, 4.9-17.3]), close contact with a cat owner (OR 7.1 [95% CI, 4-12]), allergic rhinitis (OR 3.1 [95% CI, 1.6-5.8]), conjunctivitis (OR 4.7 [95% CI, 2-10]), and atopic dermatitis (OR 2.2 [95% CI, 1-4.7]). Conclusion: We observed an increase in the prevalence of cat allergy among children during the COVID-19 pandemic. Care must be taken in terms of anaphylaxis in patients who were cat sensitized.

Risk stratification through allergy history: single-centre experience of specialized COVID-19 vaccine clinic.

Anaphylaxis is a rare side-effect of COVID-19 vaccines. To (a) provide direct advice and reassurance to certain persons with a history of anaphylaxis/complex allergy, in addition to that available in national guidelines, and (b) to provide a medically supervised vaccination, a specialist regional vaccine allergy clinic was established. The main objective was to determine if risk stratification through history can lead to safe COVID-19 vaccination for maximum population coverage. A focused history was taken to establish contraindications to giving COVID-19 vaccines. People who reported a high-risk allergy history were given a vaccine not containing the excipient thought to have directly caused previous anaphylaxis. All vaccines were monitored for 30 min after administration. A total of 206 people were vaccinated between 6 July 2021 and 31 August 2021; Comirnaty (Pfizer-BioNTech) (n = 34), and Janssen (n = 172). In total, 78% were women. Ninety-two people (45%) reported a high-risk allergy history. There were no cases of anaphylaxis. Three people developed urticaria and one of these also developed transient tachycardia. One vaccinee developed a pseudoseizure. Two of 208 people (<1%) referred during this time declined vaccination based on personal preference, despite the assessment of low clinical risk. In our experience, all vaccines with high-risk allergy histories were administered Pfizer BioNTech or Janssen Covid-19 vaccines uneventfully following screening based on allergy-focussed history. Our data support that drug allergy is not associated with a higher risk of vaccine-related anaphylaxis but may act to guide the administration of alternate vaccines to people with polyethylene glycol/polysorbate 80/trometamol allergies or anaphylaxis after the first dose.

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.

BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Incidence of immediate allergic reactions to mRNA COVID-19 vaccines in adults with drug allergies and other allergic disorders.

Concerns have been raised about allergic reactions to messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccines. A history of allergic reactions, including anaphylaxis to drugs, has been frequently reported in individuals with anaphylaxis to mRNA vaccines. To estimate the rate of immediate allergic reactions in patients with a history of drug allergy or other allergic disorders. We included adult patients who had received at least 1 dose of an mRNA COVID-19 vaccine at the Special Hospital for Pulmonary Diseases between March 1, 2021, and October 1, 2021, and who reported a history of drug allergy or other allergic diseases (asthma, allergic rhinitis, atopic dermatitis, food or insect venom allergy, mastocytosis, idiopathic anaphylaxis, acute or chronic urticaria, and/or angioedema). Immediate allergic reactions, including anaphylaxis, occurring within 4 hours of vaccination were recorded. Six immediate allergic reactions were noted in the cohort of 1679 patients (0.36%). One patient experienced anaphylaxis (0.06%), which resolved after epinephrine administration, and the other reactions were mild and easily treatable. Most patients with a history of allergies can safely receive an mRNA COVID-19 vaccine, providing adequate observation periods and preparedness to recognize and treat anaphylaxis.

Reporting of Allergic Reactions During Pfizer-BioNTech BNTT162B2 Vaccination in Israel.

BACKGROUND: In December 2020, the Israeli Ministry of Health launched a national vaccination campaign against SARS-CoV-2. Concomitant sporadic reports on anaphylactic responses in other countries raised safety concerns at the outset of this operation. OBJECTIVE: To characterize reports on allergic reactions to coronavirus disease 2019 vaccines. METHODS: Allergy events were reported by health care professionals throughout the country to Israeli Ministry of Health Division of Epidemiology via a Web-based computerized national vaccine registry. The study period was from December 19, 2020 to September 13, 2021, during which 14,475,979 injections were administered. RESULTS: Allergic reactions were reported in 463 subjects, 99.3% of whom received Pfizer-BioNTech BNTT162B2. The reporting rate was 106 per million in December 2020. From January to May 2021, a reduction was observed to 66, 18, 14, eight, and zero per million, and reporting remained low until September. Mean age of subjects was 48.9 ± 16.7 years (range, 15-96 years) with a female preponderance of 78%. Epinephrine was administered in 34 subjects. Validated immediate allergy was observed in only 37 cases (8%), suggesting 2.5 to 3.3 bona fide reactions per million. In subjects with reactions classified as severe (n = 46), plausible allergy was identified in 36% to 41% of cases. A history of allergy was associated with high false reporting of immediate reactions (83%). Allergic events after the first dose did not compromise adherence to subsequent doses. CONCLUSIONS: Excessive reporting of allergy declined over time and did not affect adherence to vaccination. The existence of previous allergy may affect reporting profiles, but not the occurrence of vaccine allergy.