We read with interest Cabanillas et al’s discussion of polyethylene glycol (PEG) as a hidden allergen in BNT162b2 COVID-19 vaccine.1
We were referred to two patients in December 2020, who reacted a few minutes after the vaccination. Patient 1 was 53 years old and had no history of anaphylaxis. Patient 2 was 35 years old with well-controlled asthma, with previous shellfish and contrast media anaphylaxis. We performed allergy testing to PEG3350 and to the vaccine itself. The second doses were successfully administered via graduated dosing.
Five minutes after her first vaccination, Patient 1 experienced dizziness, tingling lips and mouth, chest tightness, flushing of the face, palpitations and sudden tenesmus. She remained normotensive. Nursing has documented facial erythema, swelling of the lips, angioedema, difficulty breathing, a feeling of tightness in the throat, and a feeling of dread. The patient challenged throat tightness or angioedema 5 days later. Code blue has been called. Her symptoms improved quickly with 0.5 mg IM epinephrine and IV fluids.
Patient 2 experienced a feeling of tight throat, mild itching in the mouth, profound weakness, shortness of breath, and difficulty breathing 2-3 minutes after vaccination. Nursing records indicated angioedema. Code blue has been called. No vital signs were taken. Epinephrine 0.5 mg IM was administered. She was transferred to the emergency room and experienced a second wave of shortness of breath, tightness in her throat, and documented wheezing. Salbutamol, methylprednisolone and diphenhydramine were given with improvement.
Both patients were referred for urgent allergy assessment. The PEG3350 skin test two weeks after the initial reaction was negative. Patient 2 was challenged orally with PEG3350 without reaction. None of the patients had known allergy to PEG. The literature on PEG allergies suggests that tolerating higher molecular weight formulations implies tolerance to lower molecular weight formulations.2 As a result, it was reassuring that our patients tolerated PEG3350, suggesting that they would tolerate PEG2000 in the vaccine.2, 3 That said, more recent work suggests that native PEG skin tests may be falsely negative. Tests on pegylated liposomes, which look more like PEG in the vaccine, may improve sensitivity.4
We got a vaccine that would otherwise be thrown away (leftovers) for skin testing. Full strength skin tests were performed without reaction. Skin tests for dilution (1:10) and full strength vaccine (1: 1) were also negative. A healthy control confirmed that there was no irritation from the vaccine.
As there were no reports of administration of second doses to high-risk patients, we administered second doses to the emergency room using a graduated dosing schedule (Table 1), following the protocols described previously.5 The regimen used 0.05 ml of the remainder of the vaccine, in addition to the dose assigned to the patient. This has limited vaccine waste. The patients were premedicated with 40 mg of prednisone the day before and the day of the second dose, and 10 mg of cetirizine. This regimen was extrapolated from the literature describing premedication for reactions to contrast media, in order to attenuate reactions mediated by mast cells and T cells. Mast cell-mediated reactions were considered to be possible, since skin tests did not confirm IgE reactions. Both patients received their doses successfully with no objective reaction. Patient 1 described warmth on her face with the final graduated dose, but had no visible flushing or hemodynamic changes.
|Solution||Volume (equivalent volume of vaccine)||Time after previous dose|
|Diluted vaccine, 1:10||0.1 ml (0.01 ml)||10 minutes|
|Diluted vaccine, 1:10||0.4 ml (0.04 ml)||10 minutes|
|Full strength vaccine||0.05 ml||15 minutes|
|Full strength vaccine||0.10 ml||15 minutes|
|Full strength vaccine||0.15 ml||15 minutes|
As discussed by Cabanillas et al, PEG allergy testing should be considered when patients respond to Pfizer vaccine; in case of negative result, a test for pegylated liposomes should be considered.4 As Troelnikov did and in our study, skin testing on vaccine scraps is also suggested.4
Our two patients successfully received their second dose via a graduated dosing protocol. Premedication has been extrapolated from the literature on non-IgE reactions to contrast media, as skin tests have not confirmed allergy to IgE. Future administration of the protocol without premedication may be considered.
As with other vaccines, patients with severe reactions to COVID-19 vaccines can safely undergo allergy testing and vaccine desensitization.
CONFLICT OF INTEREST
The authors have no conflicts of interest to declare. Both contributed equally to the work undertaken for the allergy assessment and writing of this article.
Both patients provided written informed consent for the protocol and publication of their cases.