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

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Basophil reactivity to BNT162b2 is mediated by PEGylated lipid nanoparticles in patients with PEG allergy.

BACKGROUND: The mechanisms underpinning allergic reactions to the BNT162b2 (Pfizer) COVID-19 vaccine remain unknown, with polyethylene glycol (PEG) contained in the lipid nanoparticle suspected as being the cause. OBJECTIVE: Our aim was to evaluate the performance of skin testing and basophil activation testing to PEG, polysorbate 80, and the BNT162b2 (Pfizer) and AZD1222 (AstraZeneca) COVID-19 vaccines in patients with a history of PEG allergy. METHODS: Three known individuals with PEG allergy and 3 healthy controls were recruited and evaluated for hypersensitivity to the BNT162b2 and AZD1222 vaccines, and to related compounds by skin testing and basophil activation, as measured by CD63 upregulation using flow cytometry. RESULTS: We found that the BNT162b2 vaccine induced positive skin test results in patients with PEG allergy, whereas the result of traditional PEG skin testing was negative in 2 of 3 patients. One patient was found to be cosensitized to both the BNT162b2 and AZD1222 vaccines because of cross-reactive PEG and polysorbate allergy. The BNT162b2 vaccine, but not PEG alone, induced dose-dependent activation of all patients' basophils ex vivo. Similar basophil activation could be induced by PEGylated liposomal doxorubicin, suggesting that PEGylated lipids within nanoparticles, but not PEG in its native state, are able to efficiently induce degranulation. CONCLUSIONS: Our findings implicate PEG, as covalently modified and arranged on the vaccine lipid nanoparticle, as a potential trigger of anaphylaxis in response to BNT162b2, and highlight shortcomings of current skin testing protocols for allergy to PEGylated liposomal drugs.

Drug allergy management in the elderly.

PURPOSE OF REVIEW: Drug allergy management has previously not been emphasized in the elderly. However, the geriatric population poses several unique characteristics, challenges for drug allergy testing and considerations in the management. Especially in the era of COVID-19, the elderly population is a vulnerable cohort and reviewing the management during this unprecedented time is both timely and relevant. RECENT FINDINGS: In recent years, larger scale studies focusing on the epidemiology and prevalence trends of drug allergies among older adults has been summarized in this review. Emphasis on anaphylaxis in the older adults has been studied. SUMMARY: There are many implications of these findings. Epidemiological studies are useful in realizing the burden and spectrum of drug allergies on our healthcare system. It has allowed us to identify certain barriers in drug allergy management and develop ways to overcome these challenges through. Lastly, we have proposed an approach to drug allergy management based on previous studies as well as from our perspective and local experience.

Optimizing investigation of suspected allergy to polyethylene glycols.

BACKGROUND: Polyethylene glycols (PEGs) are polymers of varying molecular weight (MW) used widely as excipients in drugs and other products, including the mRNA vaccines against coronavirus disease 2019. Allergy to PEGs is rare. Skin testing and graded challenge carries a high risk of inducing systemic reactions. OBJECTIVE: We evaluated skin prick test (SPT) results and in vitro reactivity over time to different MW PEGs and assessed cross-sensitization patterns in PEG allergy. METHODS: Ten patients with previously diagnosed PEG allergy underwent SPT twice with PEGs 26 months apart. Lower MW (PEG 300, 3000, 6000) were tested, followed by PEG 20,000, in stepwise, increasing concentrations. Cross-sensitization to polysorbate 80 and poloxamer 407 was assessed. SPT was performed in 16 healthy controls. In vitro basophil histamine release (HR) test and passive sensitization HR test were performed in patients and controls. RESULTS: Patients previously testing positive on SPT to PEG 3000 and/or 6000 also tested positive to PEG 20,000. Patients with a longer interval since diagnosis tested negative to lower MW PEGs and positive mainly to higher concentrations of PEG 20,000. Three patients developed systemic urticaria during SPT. Eight patients showed cross-sensitization to poloxamer 407 and 3 to polysorbate 80. All controls tested negative. In vitro tests showed limited usefulness. CONCLUSIONS: Skin test reactivity to PEG can decrease over time, but titrated SPT with increasing concentrations of PEG 20,000 can be diagnostic when lower MW PEGs test negative. To avoid systemic reactions, stepwise SPT is mandatory.

Are the Allergic Reactions of COVID-19 Vaccines Caused by mRNA Constructs or Nanocarriers? Immunological Insights.

The Food and Drug Administration (FDA) has recently authorized the two messenger RNA (mRNA) vaccines BNT162b2 and mRNA-1273 for emergency use against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the COVID-19 coronavirus disease. BNT162b2 and mRNA-1273 vaccines were developed by Pfizer-BioNTech and Moderna, respectively, in 2020. The United Kingdom, Bahrain, Canada, Mexico, United States, Singapore, Oman, Saudi Arabia, Kuwait, and European Union began their vaccination programs with the BNT162b2 vaccine, while the United States and Canada also started the mRNA-1273 vaccination program in mid December 2020. On 28th December 2020, studies reported severe allergic reactions in people who received the BNT162b2, and few people who received the mRNA-1273 vaccine. Authors of the letter thus attempt to explore possible causes of anaphylaxis following COVID-19 vaccination.

Anaphylaxis associated with the mRNA COVID-19 vaccines: Approach to allergy investigation.

Reports about cases of anaphylaxis to mRNA vaccines have created anxiety in the community and could increase vaccine hesitancy in the population. There are no standardized protocols for allergy testing to mRNA vaccines. PEG is currently the only excipient in both vaccines with recognized allergenic potential. Allergy to PEG has been reported with increasing frequency over recent years, often in patients who had repeated systemic allergic reactions/anaphylaxis to several classes of drugs before diagnosis. Proposed protocols are based on current knowledge about potential mechanisms of anaphylaxis associated with the mRNA vaccines, and the assumption that polyethylene glycol (PEG) is the most likely culprit. Allergy testing to PEGs and mRNA vaccines is complex and carries the risk of anaphylaxis and should be conducted in a specialist drug allergy center. Appropriate PEG-free emergency medical treatment and supervision should be readily available.

Allergy to COVID-19 vaccines: A current update.

Adverse allergic reactions due to the administration of the vaccines developed for the protection of coronavirus disease 2019 (COVID-19) have been reported since the initiation of the vaccination campaigns. Current analyses provided by the Center for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) in the United States have estimated the rates of anaphylactic reactions in 2.5 and 11.1 per million of mRNA-1273 and BNT162b2 vaccines administered, respectively. Although rather low, such rates could have importance due to the uncommon fact that a large majority of the world population will be subjected to vaccination with the aforementioned vaccines in the following months and vaccination will most likely be necessary every season as for influenza vaccines. Health regulators have advised that any subject with a previous history of allergy to drugs or any component of the vaccines should not be vaccinated, however, certain misunderstanding exists since allergy to specific excipients in drugs and vaccines are in occasions misdiagnosed due to an absence of suspicion to specific excipients as allergenic triggers or due to inaccurate labeling or nomenclature. In this review, we provide an updated revision of the most current data regarding the anaphylactic reactions described for BNT162b2 vaccine, mRNA-1273 vaccine, and AZD1222 vaccine. We extensively describe the different excipients in the vaccines with the potential to elicit systemic allergic reactions such as polyethylene glycol (PEG), polysorbates, tromethamine/trometamol, and others and the possible immunological mechanisms involved.

Potential mechanisms of anaphylaxis to COVID-19 mRNA vaccines.

Anaphylaxis to vaccines is historically a rare event. The coronavirus disease 2019 pandemic drove the need for rapid vaccine production applying a novel antigen delivery system: messenger RNA vaccines packaged in lipid nanoparticles. Unexpectedly, public vaccine administration led to a small number of severe allergic reactions, with resultant substantial public concern, especially within atopic individuals. We reviewed the constituents of the messenger RNA lipid nanoparticle vaccine and considered several contributors to these reactions: (1) contact system activation by nucleic acid, (2) complement recognition of the vaccine-activating allergic effector cells, (3) preexisting antibody recognition of polyethylene glycol, a lipid nanoparticle surface hydrophilic polymer, and (4) direct mast cell activation, coupled with potential genetic or environmental predispositions to hypersensitivity. Unfortunately, measurement of anti-polyethylene glycol antibodies in vitro is not clinically available, and the predictive value of skin testing to polyethylene glycol components as a coronavirus disease 2019 messenger RNA vaccine-specific anaphylaxis marker is unknown. Even less is known regarding the applicability of vaccine use for testing (in vitro/vivo) to ascertain pathogenesis or predict reactivity risk. Expedient and thorough research-based evaluation of patients who have suffered anaphylactic vaccine reactions and prospective clinical trials in putative at-risk individuals are needed to address these concerns during a public health crisis.

Management of Allergic Diseases During COVID-19 Outbreak.

PURPOSE OF REVIEW: The coronavirus disease 2019 (COVID-19) has challenged healthcare system capacities and safety for health care workers, reshaping doctor-patient interaction favoring e-Health or telemedicine. The pandemic situation may make difficult to prioritize patients with allergies diseases (AD), face-to-face evaluation, and moreover concern about the possible COVID-19 diagnosis, since COVID-19 shared many symptoms in common with AD. Being COVID-19 a novel disease, everyone is susceptible; there are some advances on vaccine and specific treatment. We evaluate existing literature on allergic diseases (AD): allergic rhinitis, asthma, food allergy, drug allergy, and skin allergy, and potential underlying mechanisms for any interrelationship between AD and COVID-19. RECENT FINDINGS: There is inconclusive and controversial evidence of the association between AD and the risk of adverse clinical outcomes of COVID-19. AD patients should minimize hospital and face-to-face visits, and those who have used biologics and allergen immunotherapy should continue the treatment. It is essential to wear personal protective equipment for the protection of health care workers. Social distancing, rational use of facemasks, eye protection, and hand disinfection for health care workers and patients deserve further attention and promotion. Teleconsultation during COVID-19 times for AD patients is very encouraging and telemedicine platform can provide a reliable service in patient care.