1. Introduction

Data are sparse on the risk of allergic reactions associated with COVID-19 infection and COVID- 19 vaccination among individuals with food allergies. We aimed to assess the effect of COVID-19 infection and the safety of COVID-19 vaccines among patients with milk allergies.

Milk allergy is an IgE mediated immune system response to milk and is one of the most common food allergies with a global incidence estimated at 2% to 7.5% in the first year of life [1]. Initial reports on COVID vaccine safety raised concern regarding increased risk for allergic reactions in those with a history of anaphylaxis following the Pfizer-BioNTech BNT162b2 (hereafter referred to as BNT162b2) and the Moderna mRNA-1273 (hereafter referred to as mRNA-1273) COVID-19 vaccine [1-2]. The current government guidelines do not involve any restrictions for COVID-19 vaccination for children with milk allergy. However, despite the very low risk, there is a lack of safety data, which may contribute to vaccine hesitancy [2]. We aimed to assess the safety of COVID-19 vaccines in a cohort of children with milk allergy.

2. Methods

From June 2022 - June 2023, we contacted families with patients aged 4-30 years old from a previously established registry of children with milk allergies recruited for oral immunotherapy from two allergy clinics in Montreal, Canada. All children with milk allergies (vaccinated or not) who were reachable by phone and consented to participate in the study were included in the analysis.

Data was collected at study entry with a questionnaire on demographics and comorbidities. Our standardized COVID-19 questionnaire queried on COVID-19 vaccination status and on the post-vaccination development of urticaria/angioedema, respiratory or gastrointestinal symptoms, anaphylaxis (defined as a reaction involving at least two systems and/or hypotension) or any other symptom [4]. An additional questionnaire was given to participants infected with COVID-19 to assess their symptoms.

All data analysis was performed using R version 4.3.1. The demographic data and the association of common post-vaccination symptoms with first and second COVID-19 vaccination visits were analyzed via generalized estimating equation logistic regression using the R package geepack . The statistical difference in children reporting side effects after the first and second doses of vaccination was calculated using the Chi-Square test.

A total of 50 patients with challenge-confirmed milk allergy undergoing oral immunotherapy treatment at the Montreal Children’s Hospital were included in the study. Thirty (60%) were male and their median age was 17 (interquartile range (IQR) = 7.5).

3. Results

Five children (10.0%) were not vaccinated (Table 1) as they have all previously been infected with COVID-19. One child (2.0%) only received the first dose of the COVID-19 vaccine and not the second dose for unspecified reasons.

Table 1: Patient demographics, comorbidities.

NA: Not applicable

Forty-five children (90.0%) received the first dose of the COVID-19 vaccine (Tabel 1), 42 (93.3%) received BNT162b2 and 3 (6.7%) received mRNA-1273. Following vaccination, 23 (51.1%) did not experience any symptoms, 18 (40.0%) had an injection site reaction (hereafter shown as ISR, i.e., redness, soreness, swelling), three patients (6.7%) reported flu-like symptoms (chills, fatigue, arthralgia, headache, mild fever, myalgia), and 1 patient (2.2%) reported chest discomfort or palpitations (Table 2).

Table 2: Medication and side effects after COVID-19 infection and first and second doses of COVID-19 vaccine.

NA: Not applicable

¹One patient took both Acetaminophen and Ibuprofen

Fourty-four children (88.0%) received the second dose of the COVID-19 vaccine (Table 1), 39 (88.6%) received BNT162b2 and 5 (11.4%) received mRNA-1273. Twenty-five (56.8%) did not report any post-vaccination symptoms, 17 patients (38.6%) reported ISR and 2 patients reported flu-like symptoms (4.6%) (Table 2).

For both the first and second doses of COVID-19 vaccines (BNT162b2 and RNA-1273), no patients had been infected by COVID-19 at the time of vaccination. Additionally, no patients reported any allergic reactions such as respiratory symptoms after vaccination. Furthermore, there was no statistically significant difference (chi-square statistic= 0.63, P-value = 0.89 > 0.05) when done the Chi-Square test between the proportion of children having reported each type of side effect after the first and second-dose vaccines (Table 2).

A total of 32 patients (64.0%) had been infected by COVID-19. Most infected children (28, 87.5%) reported flu-like symptoms, three (9.4%) reported respiratory symptoms which seemed to be an allergic reaction and one (3.1%) was asymptomatic. At the time of infection, all 32 patients had not been vaccinated (Table 1).

Our results are in line with previous studies in adults suggesting that 99.22% of patients with previous severe allergic diseases (mainly drugs) tolerated mRNA vaccination with no reaction [5]. Another study suggested that the rate of allergic reactions, particularly anaphylactic reactions to the BNT162b2 vaccine, is higher than for other commonly used vaccines, though they can be safely immunized by using an algorithm [4]. Even though there have been incidents like the two employees of the National Health Service (NHS) in England developing severe allergic reactions after being administered the COVID-19 vaccine as they were allergic to the vaccine components, such cases are extremely rare [6].

4. Conclusion

While our study has provided valuable insights into the safety of COVID-19 vaccination in children with milk allergies, it is important to acknowledge its inherent limitations. Our research focused primarily on children with milk allergies, and the generalizability of our findings to broader populations requires further investigation through larger-scale studies. Moreover, the low sample size reduces the likelihood of identifying adverse reactions, which are rare complications of COVID-19 vaccination in the general population but may still be more common among milk allergy patients.

Therefore, while our results suggest minimal risk for allergic reactions in children with milk allergies, a comprehensive risk assessment framework that considers various factors, including patient history, vaccine components, and potential cross-reactivity, remains an area for future exploration. As our understanding of COVID-19 vaccination and allergic responses evolves, it is imperative to continue refining our approach to ensure the safety and well-being of all individuals.

Statements and Declarations

Funding Sources: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Conflicts of Interests: The authors have no relevant financial or non-financial conflict of interests to disclose.

Consent to participate: Informed consent was obtained from all individual participants included in the study.

Ethics Committee: This study is approved by the McGill university ethics committee.

References

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