Patients with a previous allergy history and women are at increased risk of rare anaphylactic reaction to mRNA COVID-19 vaccines

1. A case series of 22 patients found that women and patients with an allergy history were more likely to have experienced an anaphylactic reaction to the mRNA COVID-19 vaccine.

2. An IgG-mediated reaction to polyethylene glycol (PEG) was found to be the most frequent mechanism of reactivity amongst this sample.

Evidence Rating Level: 4 (Below Average)

Study Rundown: The development of a vaccine against COVID-19 has dramatically altered the course of the present pandemic. As expected with the introduction of any novel intervention to the public, reports of adverse events including anaphylactic reactions have occurred with the vaccine’s widespread distribution. The prevalence and nature of hypersensitivity reactions to the COVID-19 vaccine, and mRNA vaccines in general, are poorly understood. The present study sought to describe the immunological mechanisms driving anaphylaxis associated with mRNA COVID-19 vaccination. A case series of 22 patients recruited from the Stanford Research Repository was conducted. 91% of the included patients were women, and their mean age was 40.9 years (range 26-58). 68% had a documented history of allergic reactions most commonly to antibiotics (45%). True anaphylactic reactions to the COVID-19 vaccine were thought to have occurred in 17 of 22 patients (77%), all of which resolved. 10 patients underwent skin prick testing, with 1 individual (10%) reacting to the same brand of COVID-19 vaccine that they had previously received. Zero patients demonstrated a positive test following PEG or Polysorbate 80, another vaccine component.  However, the bloodwork demonstrated that all patients had activated basophils in response to the vaccine, and most (10/11, 91%) also demonstrated basophil activation in response to PEG specifically. Warren et al. concluded that anaphylactic reactions to mRNA COVID-19 vaccines are more likely to occur in women and in patients with a previous history of allergies. This study contributes important initial data to understanding the risk factors and mechanisms driving hypersensitivity reactions to the COVID-19 vaccine. Considering the novelty of this technology and the ongoing politicization surrounding it, it is imperative that the vaccine’s safety profile be well understood. The major pitfall of this study was it’s case series design and extremely small sample size. As a hypothesis-generating study, this work should be followed with larger studies to validate the findings reported here in a broader population.

Click to read this study in JAMA Network Open

Relevant Reading: Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer BioNTech COVID-19 vaccine

In-Depth [case series]: Eligible patients were first identified through a search of the Stanford Research Repository hospitals’ databases for several diagnostic codes corresponding to anaphylaxis within 3 hours of receiving a COVID-19 vaccine. 4,212,410 patients’ health data was available through this repository and 148 anaphylaxis diagnostic codes were found. A thorough chart review of clinical notes excluded 126 incidents coded as anaphylaxis and maintained a pool of 22 eligible patients. Allergic reactions were defined using pre-specified criteria and graded using the Brighton scale. Skin prick testing was done using standardized methodology with a histamine sample as a positive control and normal saline as a negative control. Basophil activation was measured through blood allergy testing using a heparin preservative and flow cytometry analysis. Finally, immunochemistry testing was used to assess for anti-PEG immunoglobulins using the same blood sample. No statistical analysis was performed. The most common known allergens amongst the sample were as follows: antibiotics (45%), foods (41%), non-antibiotic medications (36%). Only 10 patients underwent skin prick testing, and only 11 underwent a blood draw for immunological analysis. To determine the mechanism driving basophil activation and subsequent hypersensitivity, an enzyme-linked immunosorbent assay was performed to measure IgG and IgE responses to PEG, respectively.

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