June 7, 2022 – Understanding the Role and Impact of Poly (Ethylene Glycol) (PEG) on Nanoparticle Formulation: Implications for COVID-19 Vaccines “The increased use of nanoparticles as contrast agents or in drug delivery, along with the introduction of mRNA vaccines encapsulated in PEGylated lipid nanoparticles has brought this issue to the fore. Thus, while these vaccines have proven to be remarkably effective, rare cases of anaphylaxis have been reported, and this has been tentatively ascribed to the PEGylated carriers, which may trigger complement activation in susceptible individuals.”
March 7, 2022 – Hypersensitivity Reactions to COVID-19 Vaccines—Identify High-Risk Children and Vaccinate the Rest “In patients with a history of anaphylaxis unrelated to a COVID-19 vaccine or its excipients (PEG or PS), prolonged observation time is not necessary. Referral to an allergist is recommended for children with a history of PEG and/or PS-80 allergy or a history of an immediate severe reaction (≤4 hours) after the administration of a COVID-19 vaccine. It is important to note that most patients who react to the first COVID-19 vaccine dose will be able to tolerate the second dose. Because COVID-19 vaccines are safe and effective and severe allergic reactions are rare, it is important to encourage patients to get vaccinated against COVID-19 and avoid booster delays and to refer high-risk children to an allergist.”
February 2022 – Safety of COVID-19 vaccination in patients with polyethylene glycol allergy: A case series “Since the beginning of the vaccination campaign in Quebec, 9 allergists in 6 different hospitals evaluated 12 cases of confirmed or very likely PEG allergy. Patients were offered vaccination with either an mRNA or the AstraZeneca COVID-19 vaccine after discussion of the risks and benefits. Ten patients were vaccinated with an mRNA vaccine and 2 with the AstraZeneca vaccine.
January 2022 – Updated consensus statements on COVID-19 Vaccine Allergy Safety in Hong Kong
| CS #1: People with a history of immediate-type allergic reaction with systemic symptoms to prior COVID-19 vaccination should not receive further COVID-19 vaccination until allergist evaluation. |
| CS #2: People with a history of nonimmediate type allergic reaction to prior COVID-19 vaccination which required medical attention should seek allergist advice prior to further COVID-19 vaccination. |
| CS #3: People with a history of severe immediate-type allergy to multiple classes of drugs may have an undiagnosed excipient (such as polyethylene glycol [PEG]) allergy and they may be vaccinated with a non-PEG-containing vaccine†. |
| CS #4: Allergy testing with PEG or PEG-containing surrogates appear to be poorly predictive and should not be routinely performed. In cases where these tests are used, results should be interpreted in the context of a detailed clinical history by an allergist. |
| CS #5: Patients with allergic rhinitis, asthma, atopic dermatitis, chronic urticaria, drug and food allergies, and anaphylaxis unrelated to COVID-19 vaccines (without other precautions) do not need to see an allergist for evaluation of COVID-19 vaccine allergy risk. |
| CS #6: Healthcare providers should be sufficiently prepared to recognize and treat allergic reactions properly, with adrenaline and antihistamines readily available. |
| CS #7: When an immediate-type allergic reaction following COVID-19 vaccination is suspected, blood for serum tryptase should be saved from 30 minutes to 4 hours (preferably within 2 hours) of symptom onset. |
| CS #8: People should be routinely observed for at least 15 minutes after COVID-19 vaccination. Those at higher risk of COVID-19 vaccine-associated allergic reactions should be observed for at least 30 minutes after vaccination. |
| CS #9: Full excipient lists should be mandated and made available in all product inserts of registered drugs. |
June 2021 – Other excipients than PEG might cause serious hypersensitivity reactions in COVID‐19 vaccines “Lipid SM‐102 (patented ionizable lipid cholesterol) Moderna Comirnaty,
May 14, 2021 – Interim considerations: preparing for the potential management of anaphylaxis after COVID-19 vaccination “Clarification on contraindications and precautions. People with a known (diagnosed) allergy to PEG, another mRNA vaccine component, or polysorbate, have a contraindication to vaccination. People with a reaction to a vaccine or injectable therapy that contains multiple components, one of which is PEG, another mRNA vaccine component or polysorbate, but in whom it is unknown which component elicited the immediate allergic reaction have a precaution to vaccination.”
April 4, 2021 – Adverse reactions to COVID-19 vaccines: A practical approach [Correction added on 7 May 2021, after first online publication: Key Messages were omitted and have been reinstated in this version.] “Polysorbate 80 (PS80; Tween 80) is derived from polyethoxylated sorbitan and oleic acid. PS80 is used as a common emulsifier and stabilizer in the food industry and excipient in medications and vaccines such as influenza, hepatitis B and human papillomavirus (HPV) vaccines.In the United States, PS80 is an excipient in 6821 FDA approved medications. It is one of the excipients in the Astra Zeneca vaccine. The hydrophilic groups in PS80 are polyethers also known as polyoxyethylene groups, which are polymers of ethylene oxide. PEG and PS80 share an allergenic epitope, that is the repeating polyether domain. Immediate hypersensitivity to PEG 3350 with skin test cross-reactivity to PS80 has been reported but its wider clinical relevance is unclear.“
March 3, 2021 – Allergenic components of the mRNA-1273 vaccine for COVID-19: Possible involvement of polyethylene glycol and IgG-mediated complement activation “Allergic reactions to such PEGylated lipids can be IgE‐mediated,but may alsoresult from complement activation‐related pseudoallergy (CARPA) that has been described insimilar liposomes. In addition, mRNA‐1273 also contains tromethamine (trometamol), which has been reported to cause anaphylaxis to substances such asgadolinium‐based contrast media.”
December 17, 2020 – Anaphylaxis to the first COVID-19 vaccine: is polyethylene glycol (PEG) the culprit? “The vaccine contains a number of excipients and lipids, one of them based on PEG-2000. This is currently the only excipient in the vaccine with recognised allergenic potential. The severity and rapid onset of the two reported reactions to the vaccine further increase suspicion towards PEG. … However, allergy to PEG, also often called macrogol, has been reported with increasing frequency over recent years, Patients have usually had repeated systemic allergic reactions/anaphylaxis before diagnosis. A typical history is of severe allergic reactions to several classes of drugs, for example, penicillin, laxatives, injected corticosteroids, or antacids, all containing PEG. Symptoms are of rapid onset, usually within minutes, and typically result in severe generalised pruritus, urticaria, angioedema, hypotension, or difficulty in breathing. Reactions are more severe with higher doses and with higher-molecular-weight PEGs.”
November 25, 2021 – The Polysorbate containing AstraZeneca COVID-19 vaccine is tolerated by polyethylene glycol (PEG) allergic patients “Initial diagnosis was made following anaphylaxis to at least one PEG-containing drug with positive skin tests to PEG (6 skin prick tests (SPT) to PEG, 1 intradermal test to PEG and 1 SPT to Movicol). Patients were offered vaccination with the AstraZeneca COVID-19 vaccine (<100 mcg of PS80 per dose4) in clinic. All patients underwent SPTs to PS80 (20%) and to the AstraZeneca COVID-19 vaccine prior to vaccination. IV access was obtained prior to vaccination. If a patient had positive SPT to PS80 and AstraZeneca vaccine, then a split dose was given. Patients were monitored for 1 h following vaccination in our drug allergy clinic with full access to anaphylaxis and resuscitation treatment. Blood pressure, heart rate and oxygen saturations were measured when the patient entered the drug allergy clinic, and at 30 min and 1 h into the challenge. Written informed consent was obtained from all patients.”