mRNA COVID-19 vaccine: Safe in people with allergy history?

A large prospective, observational study has suggested that while individuals with a history of high-risk allergy may have an increased risk of allergic reactions following receipt of a messenger RNA (mRNA) COVID-19 vaccine, they are still able to receive both vaccine doses.

“We found that a self-reported history of high-risk allergy was associated with a 2.5-fold higher risk for self-reported allergic reactions in the 3 days after vaccination and an approximately fourfold higher risk of hives and angioedema specifically,” the authors said.

“This study not only highlighted that high-risk allergy history was associated with allergy symptoms after COVID-19 vaccination but also supported the overall safety of mRNA vaccines in all eligible individuals,” they added.

“The results … can help guide expectations for patients with high-risk allergy histories,” noted lead author Dr Lily Li from Brigham and Women’s Hospital, Boston, Massachusetts, US.

The researchers obtained data of 52,998 individuals (mean age 42 years, 72 percent female) who were employees of the Mass General Brigham healthcare system, US, and who had received ≥1 dose of a mRNA COVID-19 vaccine between December 14, 2020 and February 1, 2021 (97.6 percent completed two doses). Only individuals who completed ≥1 post-vaccination symptom survey within 3 days of either dose of vaccination* were included.

Through a pre-vaccination questionnaire, 0.9 percent (n=474) had a self-reported history of high-risk allergy (prior severe allergic reaction to a vaccine, injectable medication [45.8 percent], or other allergen [47 percent]). Nine individuals had a history of a severe allergic reaction to polyethylene glycol (PEG) or PEG-containing products. Individuals with a history of high-risk allergy had a 30-minute observation period following vaccination, while those without a history of severe allergy had a 15-minute observation period.

Compared with individuals without a history of high-risk allergy, those with were older (46 vs 42 years) and were more likely to have atopic disease (16.7 percent vs 8.7 years; p<0.001), anxiety (28.9 percent vs 23.9 percent; p=0.01), hypertension (14.6 percent vs 10.9 percent; p=0.01), or malignant neoplasm (4.0 percent vs 2.4 percent; p=0.03). There was also a higher percentage of women (80.8 percent vs 71.9 percent) and Black individuals (9.5 percent vs 4.8 percent) in the group with vs without high-risk allergy.

The incidence of self-reported allergic reactions** in the first 3 days after the first or second dose of a mRNA COVID-19 vaccine was higher among individuals with vs without a history of high-risk allergy (11.6 percent vs 4.7 percent). [JAMA Network Open 2021;4:e2131034]

The most common reactions were mild symptoms of non-injection site rash or itching (2.7 percent), respiratory symptoms (1.3 percent), hives (0.9 percent), and angioedema (0.6 percent).

Individuals with a history of high-risk allergy were at greater risk of developing allergic reactions after receipt of an mRNA COVID-19 vaccine (adjusted relative risk [adjRR], 2.46, 95 percent confidence interval [CI], 1.92–3.16).

The most common post-vaccination allergic reactions among those with a history of high-risk allergy were hives (3.4 percent vs 0.9 percent; adjRR, 3.81, 95 percent CI, 2.33–6.22) and angioedema (2.7 percent vs 0.6 percent; adjRR, 4.36, 95 percent CI, 2.52–7.54). The risks of these reactions were more common after the first vaccine dose (adjRRs, 5.47 and 6.33, respectively, vs 2.81 and 2.15, respectively after the second dose).

The results were consistent regardless of sex, age, race, and vaccine manufacturer (Moderna and Pfizer-BioNTech). Older age, Black race, higher Charlson comorbidity index score, and receipt of Moderna (vs Pfizer BioNTech vaccine) were tied to an increased risk of allergic reactions post-vaccination (RRs, 1.00, 1.69, 1.04, and 1.49, respectively), while male sex (vs female) was tied to a lower risk (RR, 0.66).

Severe allergic reactions within 3 days of vaccination were only reported by 0.3 percent (n=140), six of whom had a history of high-risk allergy. A history of high-risk allergy was tied to a fivefold risk of post-vaccination severe allergic reactions (adjRR, 5.20).

Allergy history not a deal-breaker?

Based on several guidelines, the patients with a history of severe allergy to injectable medications or vaccines or PEG may have been ineligible for the mRNA COVID-19 vaccines.

“However, following the CDC guidelines, with allergist consultation, risk stratification, and shared decision-making, all employees were able to complete the two-dose vaccine series. For the rare individuals with a history of severe allergic reactions to PEG, consultation with an allergist or immunologist is recommended because the mRNA vaccine may not be an absolute contraindication for such individuals,” the authors said. Nonetheless, they called for further studies in diverse populations to assess the safety of mRNA COVID-19 vaccines in those with PEG allergy.

“Symptoms such as hives and swelling may occur, particularly with the first vaccine dose, but most reported allergic symptoms did not impede completion of the two-dose mRNA vaccine series,” said Li.

“[This raises] the possibility that not all first-dose reactions are truly allergic or may occur through non–IgE-mediated mechanisms,” the authors added.

“We hope these data will help inform ongoing conversations with patients who are hesitant to receive COVID-19 vaccination due to allergy concerns,” said senior author Dr Kimberly Blumenthal, co-director of the Clinical Epidemiology Program, Massachusetts General Hospital, Boston, Massachusetts, US.