The document discusses allergic reactions to mRNA COVID-19 vaccines. It provides statistics on reported cases of anaphylaxis following the Pfizer and Moderna vaccines. It examines the proposed mechanisms of allergic reactions related to components like PEG and polysorbates. Guidance is presented from organizations on evaluating and managing risks of allergic reactions for first and second doses. Ongoing studies are exploring the safety of administering second doses to those with initial allergic reactions through methods like skin testing. Updates are also provided on vaccine trials in children and immunocompromised groups that demonstrate safety and efficacy.

1. Allergic Reactions to mRNA
COVID-19 Vaccines
Puttatida Chetwong, M.D.
Pediatric Allergy, Immunology and Rheumatology
King Chulalongkorn Memorial Hospital
25-Mar-2022

2. Outline
• Statistics
• Infection rate
• Vaccination rate
• Reports on allergic reactions, anaphylaxis/nonanaphylaxis
• Vaccine components, proposed mechanisms of reactions
• Guidance related to concerns of allergic reactions
• Update: COVID-19 Vaccines in Children and
Immunocompromised Patients

3. COVID-19 Data Repository by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University

4. COVID-19 Data Repository by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University

5. Dec 2020 Feb 2021 Apr 2021 Jun 201 Aug 2021 Oct 2021 Dec 2021 Feb 2022
Reports of anaphylactic reactions after first dose mRNA vaccine

6. During December 14–23, 2020, monitoring by the Vaccine
Adverse Event Reporting System detected 21 cases of anaphylaxis
after administration of a reported 1,893,360 first doses of the
Pfizer-BioNTech COVID-19 vaccine (11.1 cases per million doses);
71% of these occurred within 15 minutes of vaccination.
MMWR Morb Mortal Wkly Rep 2021;70:46–51.

7. MMWR Morb Mortal Wkly Rep 2021;70:46–51.

8. MMWR Morb Mortal Wkly Rep 2021;70:46–51.

9. Brighton Collaboration case definition
Vaccine. 2007 Aug 1;25(31):5675-84.

10. Vaccine. 2007 Aug 1;25(31):5675-84.

11. MMWR Morb Mortal Wkly Rep 2021;70:46–51.

12. MMWR Morb Mortal Wkly Rep 2021;70:46–51.

13. MMWR Morb Mortal Wkly Rep 2021;70:125–129.
During December 21, 2020–January 10, 2021, monitoring by the
Vaccine Adverse Event Reporting System detected 10 cases of anaphylaxis
after administration of a reported 4,041,396 first doses of Moderna
COVID-19 vaccine (2.5 cases per million doses administered). In nine
cases, onset occurred within 15 minutes of vaccination. No anaphylaxis-
related deaths were reported.

14. MMWR Morb Mortal Wkly Rep 2021;70:125–129.

15. Shimabukuro TT, Cole M, Su JR. JAMA. 2021;325(11):1101-2.
• Clinical characteristics of anaphylaxis
cases following both vaccines were
similar.
• There were no apparent clinical differences
between anaphylaxis cases with symptom
onset within 30 minutes and those with
symptom onset after 30 minutes.

16. Alhumaid S, et al. Allergy Asthma Clin Immunol. 2021;17(1):109.

17. Alhumaid S, et al. Allergy Asthma Clin Immunol. 2021;17(1):109.

18. Vaccine components,
proposed mechanisms of allergic reactions

19. Risma, K. A. J Allergy Clin Immunol, 147(6), 2075-2082 e2072.

20. Banerji A. J Allergy Clin Immunol Pract. 2021 Apr;9(4): 1423-1437

21. Banerji A. J Allergy Clin Immunol Pract. 2021 Apr;9(4): 1423-1437

22. Banerji A. J Allergy Clin Immunol Pract. 2021 Apr;9(4): 1423-1437

23. Risma, K. A. J Allergy Clin Immunol, 147(6), 2075-2082 e2072.

24. Guidance related to concerns of
allergic reactions

25. Dec 2020 Feb 2021 Apr 2021 Jun 201 Aug 2021 Oct 2021 Dec 2021 Feb 2022
Reports of
anaphylactic reactions
after first dose mRNA
vaccine
Feb 2021
WAO recommendations
COVID-19 vaccine-associated
anaphylaxis: A statement of the
World Allergy Organization
Anaphylaxis Committee

26. Individuals who develop a systemic allergic reaction to a vaccine should
not receive a second dose of that vaccine, nor a vaccine with similar excipients.
For example, patients who react with systemic symptoms of the Pfizer BioNTech
vaccine should not be given a second dose of this vaccine, nor should they receive a
dose of the Moderna vaccine which is also a mRNA-based vaccine which contains
PEG. Although data are not currently available as to protection offered using a
combination of different vaccines, current UK advice is that the AstraZeneca
vaccine can be used as an alternative (if not otherwise contraindicated, for
example, in a patient with a proven allergy to polysorbate 80).
World Allergy Organ J. 2021 Feb;14(2):100517.

27. Advice from the British Society for Allergy and Clinical Immunology
(BSACI) (and published by Public Health England) advises that individuals who
develop just a localized urticarial skin reaction (without systemic symptoms)
to the first dose of a COVID-19 vaccine should receive the second dose using
the same vaccine, in a setting with full resuscitation facilities (eg, a hospital);
a 30 min observation period is advised.
World Allergy Organ J. 2021 Feb;14(2):100517.

28. World Allergy Organ J. 2021 Feb;14(2):100517.

29. Dec 2020 Feb 2021 Apr 2021 Jun 201 Aug 2021 Oct 2021 Dec 2021 Feb 2022
Reports of
anaphylactic reactions
after first dose mRNA
vaccine
WAO recommendations
Apr 2021
JACI Pract
mRNA Vaccines to Prevent COVID-
19 Disease and Reported Allergic
Reactions: Current Evidence and
Suggested Approach

30. Banerji A. J Allergy Clin Immunol Pract. 2021 Apr;9(4): 1423-1437
Prior to first dose

31. Banerji A. J Allergy Clin Immunol Pract. 2021 Apr;9(4): 1423-1437
Prior to second dose

32. Dec 2020 Feb 2021 Apr 2021 Jun 201 Aug 2021 Oct 2021 Dec 2021 Feb 2022
Reports of
anaphylactic reactions
after first dose mRNA
vaccine
WAO recommendations
JACI Pract

33. Barbaud A. Allergies and COVID-19 vaccines: An ENDA/EAACI Position Paper. Allergy.2022

34. Barbaud A. Allergies and COVID-19 vaccines: An ENDA/EAACI Position Paper. Allergy.2022

35. Barbaud A. Allergies and COVID-19 vaccines: An ENDA/EAACI Position Paper. Allergy.2022

36. Barbaud A. Allergies and COVID-19 vaccines: An ENDA/EAACI Position Paper. Allergy.2022

37. Barbaud A. Allergies and COVID-19 vaccines: An ENDA/EAACI Position Paper. Allergy.2022

38. Barbaud A. Allergies and COVID-19 vaccines: An ENDA/EAACI Position Paper. Allergy.2022

39. Barbaud A. Allergies and COVID-19 vaccines: An ENDA/EAACI Position Paper. Allergy.2022

40. Barbaud A. Allergies and COVID-19 vaccines: An ENDA/EAACI Position Paper. Allergy.2022
Prior to first dose

41. Barbaud A. Allergies and COVID-19 vaccines: An ENDA/EAACI Position Paper. Allergy.2022
Prior to subsequent dose

42. AAAAI COVID-19 Response Task Force Guidance on Administration
of COVID-19 Vaccines Related to Concerns of Allergic Reactions
• All COVID-19 vaccines should be administered in a facility where each person
can be monitored for at least 15 minutes with treatment readily available for
anaphylaxis. Anyone with a history of non-anaphylactic reactions to food, oral
medication, latex, environmental, or venom allergens can safely receive either the
Pfizer or Moderna vaccine in this manner.
• Anyone with a history of anaphylaxis to food, oral medication, latex,
environmental, or venom allergies can receive either the Pfizer or Moderna vaccine
without any precautions other than a recommended 30-minute observation period.
https://education.aaaai.org/resources-for-a-i-clinicians/reactionguidance_COVID-19 Accessed on 24 Mar 2022
Guidance Prior to the First COVID-19 Vaccine Dose

43. AAAAI COVID-19 Response Task Force Guidance on Administration
of COVID-19 Vaccines Related to Concerns of Allergic Reactions
• Anyone with a history of immediate onset hypersensitivity reactions (urticaria,
wheezing, angioedema, anaphylaxis) to any prior vaccine or injected medication can
receive either the Pfizer or Moderna vaccine with a recommended 30-minute
observation period.
• Anyone with known and proven IgE mediated reactions to PEG or polysorbate
are currently advised to avoid the Pfizer and Moderna vaccines. Given the rarity of
allergies to these ingredients, it is unlikely for anyone to have this known allergy, unless
specifically evaluated by a board certified allergist and confirmed with prior skin
testing.
Guidance Prior to the First COVID-19 Vaccine Dose
https://education.aaaai.org/resources-for-a-i-clinicians/reactionguidance_COVID-19 Accessed on 24 Mar 2022

44. AAAAI COVID-19 Response Task Force Guidance on Administration
of COVID-19 Vaccines Related to Concerns of Allergic Reactions
• If a person experienced delayed onset symptoms, including
rash, swelling, lymphadenopathy, fever, fatigue, etc., then
- they should not be considered at increased risk for anaphylaxis with
the second dose
- skin testing to vaccine components is not indicated in these
situations
Guidance Prior to the Second COVID-19 Vaccine Dose
https://education.aaaai.org/resources-for-a-i-clinicians/reactionguidance_COVID-19 Accessed on 24 Mar 2022

45. AAAAI COVID-19 Response Task Force Guidance on Administration
of COVID-19 Vaccines Related to Concerns of Allergic Reactions
• If the history is highly suggestive for possible IgE-mediated
reaction to the first COVID-19 vaccine dose, then evaluation by an
allergist should be considered. Shared decision making regarding
risks and benefits of receiving a second dose should be discussed,
including options to
1) avoid,
2) receive under physician supervision, or
3) evaluation with skin testing.
Guidance Prior to the Second COVID-19 Vaccine Dose
https://education.aaaai.org/resources-for-a-i-clinicians/reactionguidance_COVID-19 Accessed on 24 Mar 2022

46. AAAAI COVID-19 Response Task Force Guidance on Administration
of COVID-19 Vaccines Related to Concerns of Allergic Reactions
• Given the speculation surrounding potential reactions to PEG or
polysorbate, skin testing protocols with non-irritant concentrations
have been published for the allergist to consider as part of their
evaluation, but are not validated or currently recommended in every
situation.
Although these vaccines do not contain polysorbate, there are
reports of cross-reactivity with PEG and future vaccines do contain
polysorbate.
Guidance Prior to the Second COVID-19 Vaccine Dose
https://education.aaaai.org/resources-for-a-i-clinicians/reactionguidance_COVID-19 Accessed on 24 Mar 2022

47. AAAAI COVID-19 Response Task Force Guidance on Administration
of COVID-19 Vaccines Related to Concerns of Allergic Reactions
• Skin testing to the vaccine is of unclear utility in evaluating
possible allergic reactions to these vaccines. The validity of this
approach has not been proven, nor have non-irritant
concentrations been determined. Further, from a public health
standpoint, the stock of vaccines is limited and (at this time) is
likely better used for vaccinations rather than evaluation of
potential reactions.
Guidance Prior to the Second COVID-19 Vaccine Dose
https://education.aaaai.org/resources-for-a-i-clinicians/reactionguidance_COVID-19 Accessed on 24 Mar 2022

48. Ongoing Trial

49. COVID Vaccine Allergy Reaction (COVAAR)
A Randomized, Placebo-controlled Crossover Study to Assess the Safety of
Administering a Second Dose of a COVID-19 mRNA Vaccine in Individuals
Who Experienced a Systemic Allergic Reaction to an Initial Dose
https://clinicalstudies.info.nih.gov/protocoldetails.aspx?id=000460-I&&query=000460-I
Aims:
a) What is the risk of recurrence of allergic reactions in individuals who had anaphylaxis or a systemic
allergic reaction after receiving the 1st dose of an mRNA COVID-19 vaccine?
b) What is/are the underlying mechanism(s) of these reactions and are there any specific biochemical,
molecular, or genetic factors that influence these reactions?
c) How likely is skin testing to predict a systemic reaction to the mRNA COVID-19 vaccines?
d) How is the immune response to mRNA vaccines impacted by variable dosing?

50. Inclusion criteria
- Aged 16-69 years.
- Must have experienced a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR
Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2 ng/mL] per modified CoFAR Grading Scale for
Systemic Allergic Reactions Version 3.0) to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine.
Patients without documented hypoxia, hypotension, or evidence of end-organ damage who were treated
with epinephrine infusion would be considered as CoFAR Grade 3 reaction and may be eligible per
investigator discretion.
- Must be at least 28 days out from their first dose of the Moderna vaccine or 21 days from their first dose of
the Pfizer-BioNTech vaccine before proceeding with the placebo or vaccine challenge in this study.
Exclusion criteria
- Experienced a Grade 4 systemic allergic reaction (per CoFAR Grading Scale for Systemic Allergic Reactions
Version 3.0) to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine.

51. Burks AW, Jones SM, Wood RA, et al. N Engl J Med. 2012;367:233-243.
CoFAR Grading Scale

52. COVID-19 Vaccines in Children and
Immunocompromised Patients

53. รศ. พญ.วนัทปรียา พงษ์สามารถ
คําแนะนําการฉีดวัคซีนป้องกันโรคโควิด-19 สําหรับเด็ก และวัยรุ่น (ฉบับที่ 5)

54. รศ. พญ.วนัทปรียา พงษ์สามารถ
คําแนะนําการฉีดวัคซีนป้องกันโรคโควิด-19 สําหรับเด็ก และวัยรุ่น (ฉบับที่ 5)

55. • A randomized, placebo-controlled,
observer-blinded, phase 3 trial
• 2260 adolescents (12-15 yr)
received BNT162b2, 1129 received
placebo
• 2 injections, 21 days apart, 30 ug
of BNT162b2 or placebo
• Noninferiority of immune
response to BNT162b2 in 12-to-
15-yr-old compared with that in
16-t0-25-year-old
• Efficacy against confirmed COVID-
19 onset at least 7 days after
second dose was 100%
N Engl J Med 2021; 385:239-250

56. N Engl J Med 2021; 385:239-250

57. N Engl J Med 2021; 385:239-250

58. N Engl J Med 2022; 386:35-46