Anaphylaxis and Coronavirus Disease 2019 vaccine: a danger relationship?

PURPOSE OF REVIEW: Anaphylactic reactions reported after Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) RNA vaccines were expected to be more frequent in atopic subjects and attributed to its polyethylene glycol component. RECENT FINDINGS: Anaphylaxis to SARS-CoV2 RNA vaccines is no more frequent than in any vaccine and direct proofs for the role of its polyethylene glycol component are lacking. SUMMARY: Vaccines against coronavirus disease 2019 (COVID-19) are an essential global intervention to control the current pandemic situation. Anaphylactic reactions have rapidly been reported after SARS-CoV2 RNA vaccines. This risk is now measured at 2.5-11/1 000 000 in the context of vaccine safety surveillance programs and only one case was documented to be due to polyethylene glycol. Suggestions for its role are indirect. The COVID-19 vaccination is rolling out vastly and surveillance programs are key to monitor severe adverse reactions, such as anaphylaxis. Anaphylaxis due to vaccine is extremely rare and specific cases should receive individualized investigation and care, highlighting the key role of allergists in the vaccination programmes.

Immunization practices and risk of anaphylaxis: a current update, comprehensive of COVID-19 vaccination data.

PURPOSE OF REVIEW: This review aims to provide an updated report in regards to the correlation between vaccines and anaphylaxis and the related risk in the population. RECENT FINDINGS: Initial reports showed higher incidence of anaphylaxis following messenger RNA COVID-19 vaccines compared with 'routine' vaccinations, likely influenced by the great attention paid to these 'new' vaccines. However, anaphylaxis has still to be considered quite rare and its incidence will be systematically reconsidered in the light of additional data collected. SUMMARY: Adverse reactions to vaccines are commonly reported but most of them are nonspecific mild events, whereas vaccine-related anaphylaxis is considered a rare event, with an incidence rate equal to 1.3 cases per million vaccine doses administered. As anaphylaxis reports usually start to be reported to passive pharmacovigilance during postmarketing surveillance, the first data are used to be influenced by under- and over-reporting and lack of denominators and following studies are needed to confirm the causal relationship. This might create an initial overcautiously approach to new immunization practices but, being anaphylaxis a potential life-threatening event, every suspected contraindication has to be deepened to maximize effectiveness and safety profile and constantly redefined not to exclude an overestimated population group who could receive the vaccine uneventfully.

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.

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.

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.