COVID19 SARS Vaccinations: Systemic Allergic Reactions to SARS-CoV-2 Vaccinations

COVID-19 Clinical Trial

— SARS  

Official title:

Systemic Allergic Reactions to SARS-CoV-2 Vaccination

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04761822
• Other study ID #: DAIT COVID-19-004
• Secondary ID: NIAID CRMS ID#:
• Status: Completed
• Phase: Phase 2
• Start date: April 7, 2021
• Est. completion date: April 27, 2022

Study information

• Verified date: November 2023
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background: Allergic reactions have been reported to occur after vaccination with both the Pfizer-BioNTech COVID-19 Vaccine and Moderna COVID-19 Vaccine. Allergic reactions range from mild to severe and include life- threatening anaphylactic reactions, although no deaths have been reported with either vaccine. This study is designed with two principal aims: - To estimate the proportions of systemic allergic reactions to the Pfizer-BioNTech COVID-19 Vaccine and the Moderna COVID-19 Vaccine in a High-Allergy/Mast Cell Disorder (HA/MCD) population, and - If the risk in the HA/MCD is demonstrable, to determine whether the proportions are higher in the HA/MCD in comparison to a representative population without severe allergies or mast cell disorders

Description:

This is a multicenter, randomized, initially blinded (masked), phase 2 trial to assess SARS-CoV-2 vaccination reactions in two populations: - One population including individuals with a history of allergic reactions or Mast Cell Disorder (HA/MCD), and - One comparison population without severe allergies or mast cell disorders. Approximately 2040 HA/MCD and 1360 comparison participants will be enrolled across participating sites in the United States. Approximately two-thirds of participants enrolled in each of the 2 groups will be female. This is because the vast majority of cases of anaphylaxis to the COVID-19 vaccines have occurred in women. Enrollment of participants who qualify only on the basis of reactions to multiple unrelated drugs will be limited to approximately 300. Enrollment of the MCD group is anticipated to be at least 200 participants, and not more than 300 participants. Participants in each population will be randomized 2:2:1:1 to receive the Pfizer-BioNTech COVID-19 Vaccine, Moderna COVID-19 Vaccine, placebo + Pfizer-BioNTech COVID-19 Vaccine, or placebo + Moderna COVID-19 Vaccine, if enrolled in the initial study period under protocol versions 1.0 -4.0. Participants enrolled under protocol version 5.0 will be randomized 2:1 to receive the Pfizer-BioNTech COVID-19 Vaccine or placebo + Pfizer-BioNTech COVID-19 Vaccine. If enrollment under protocol version 5.0 is robust and sustained, the active vaccine randomization may be changed to the Moderna COVID-19 Vaccine. Participants randomized to one of the placebo groups will receive placebo as a first dose and will receive two doses of their assigned active vaccine at subsequent visits. During the first visit, all participants will be initially-blinded to whether they are receiving placebo or vaccine, and to which vaccine they are receiving (if enrolling under protocol versions 1.0 -4.0). Due to the different dosing schedules for the Pfizer-BioNTech COVID-19 Vaccine and Moderna COVID-19 Vaccine, it will become apparent to both the site staff and the study participant which vaccine has been assigned, once the second injection visit is scheduled. However, the blind over placebo versus vaccine will remain in effect until after the second visit. During a follow-up call, scheduled 3 days after the second injection, participants will be unblinded as to whether they received placebo or active vaccine. However under protocol version 5.0, participants will be told if they received placebo as the first injection during the following up conducted 3 days after. Participants in this phase of the study will also know which company's vaccine they are receiving, as the vaccines are anticipated to be used sequentially and will also be noted in the consent form. Study Duration: Randomized and vaccinated participants will complete study participation in approximately 29 days if vaccinated with the Pfizer-BioNTech COVID-19 Vaccine, 36 days if vaccinated with the Moderna COVID-19 Vaccine. Participants enrolled under protocol versions 1.0 -4.0 will complete study participation in 50 or 64 days if administered placebo before receiving two doses of either the Pfizer-BioNTech COVID-19 Vaccine or the Moderna COVID-19 Vaccine, respectively and participants enrolled under protocol version 5.0 will complete participation in approximately 36 of 43 days, respectively, if they receive placebo first.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 746
• Est. completion date: April 27, 2022
• Est. primary completion date: April 20, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years and older

Eligibility

Inclusion Criteria:

Individuals who meet all of the following criteria are eligible for enrollment as study participants: Both groups (e.g., High-Allergy and Mast Cell Disorder (HA/MCD) Group and Comparison

Group):

1. Able to understand and provide informed consent

2. Male or non-pregnant female =12 years of age on the date of first study vaccination/placebo administration (protocol versions 1.0 - 4.0) OR male or non-pregnant female 5-17 years of age on the date of first study vaccination/placebo administration (protocol version 5.0)

3. Females of childbearing potential must have a negative pregnancy test prior to the first vaccination and placebo administration, if applicable. --If a participant becomes pregnant after receiving a placebo dose but prior to receiving study vaccination, she will be discontinued from the study

4. Females of reproductive potential° and sexually active must agree to use FDA approved methods of birth control for the duration of the study. These include hormonal contraceptives, intrauterine device, double barrier contraception (i.e., condom plus diaphragm), or male partner with documented vasectomy.

• Menopause is defined as at least 12 consecutive months without menses; if in question, a follicle stimulating hormone of =25 U/mL must be documented.
• Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation must be documented, as applicable; if documented, women with these conditions are not required to use additional contraception. High-Allergy and Mast Cell Disorder (HA/MCD) Group: Individuals who meet at least one of the following criteria are eligible for enrollment in

the HA/MCD group:

1. History of a severe allergic reaction to food(s), allergen immunotherapy, insect venom(s), or latex with use of epinephrine within the last 15 years

2. History of an Emergency Department visit with convincing evidence of a systemic allergic reaction (consistent with CoFAR Grade 3 or higher) to food(s), allergen immunotherapy, insect venom(s), or latex within the last 15 years

3. History of documented, immediate allergic reactions to 2 or more unrelated drugs within the last 15 years

4. A convincing clinical history, or a history that is accompanied by a positive skin test, of an immediate reaction to a drug, vaccine, or latex within the last 15 years

5. History of physician-diagnosed idiopathic anaphylaxis requiring epinephrine or an Emergency Department visit in the last 15 years

6. History of a physician-diagnosed mast cell disorder (e.g., mastocytosis, mast cell activation syndrome [MCAS], or hereditary alpha-tryptasemia). MCAS must meet consensus

criteria as defined below:

• Criterion A: Typical clinical signs of severe, recurrent (episodic) systemic Mast Cell Activation are present (often in form of anaphylaxis) ---Definition of systemic: involving at least 2 organ systems
• Criterion B: Involvement of Mast Cell (MC) is documented by biochemical studies --- Preferred marker: increase in serum tryptase level from the individual's baseline to plus 20% + 2 ng/ml
• Criterion C: Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production or drugs blocking mediator release or effects of MC-derived mediators
• NOTE: All 3 Mast Cell Activation Syndrome (MCAS) criteria (A + B + C) must be fulfilled to call a condition MCAS. Comparison Group: Individuals who meet all of the following criteria are eligible for enrollment in the

comparison group:

1. No history of allergic asthma or atopic dermatitis within the last 10 years

2. No history of chronic spontaneous urticaria, or angioedema

3. No history of allergic reactions to foods or insect venoms

4. No history of allergic reactions to drugs or vaccines

5. No history of anaphylaxis

6. No history of a mast cell disorder (e.g., mastocytosis, mast cell activation syndrome [MCAS], or hereditary alpha- tryptasemia) Exclusion Criteria: Individuals who meet any of these criteria are not eligible for enrollment as study

participants:

1. Inability or unwillingness of a participant and/or parent/legal guardian to give written informed consent and/or assent, as applicable, or to comply with study protocol

2. Weight less than 15 kg (33 lbs)

3. Prior receipt of any doses of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) Vaccine, Moderna COVID-19 Vaccine, or any other COVID-19 vaccine

4. History of a severe reaction to any component of the Pfizer-BioNTech COVID-19 Vaccine or Moderna COVID-19 Vaccine

5. History of contact dermatitis with confirmed patch test reaction to Prevalence of polyethylene glycol (PEG)

6. History of reaction to Doxil®

7. Known exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and still within the quarantine window

8. Symptoms consistent with acute COVID-19 infection or known COVID-19 infection (positive Polymerase chain reaction [PCR] or antigen test) and still within the quarantine window

9. Have an acute illness, including body temperature greater than 100.4 degrees Fahrenheit, within 14 days of the first study vaccination/placebo administration or 3 days prior to each subsequent vaccination

10. History of autoimmune or other disorders requiring systemic immune modulators

11. History of acute urticaria within 28 days of randomization

12. Pregnant

13. Have received any vaccines within 14 days of the first study vaccination/placebo administration or plan to receive other vaccines during the study period

14. Had any allergen immunotherapy administration within 24 hours prior to vaccination/placebo administration or plan to receive within 24 hours after vaccination/placebo administration

15. Have received a biologic therapy within 6 months of randomization

16. Use of systemic steroids for any reason within 28 days of randomization

17. Use of Zileuton® within 14 days of randomization

18. Use of any monoclonal antibody agent for treatment or prevention of COVID-19 within 3 months of randomization

19. Coronary artery disease, peripheral or cerebral vascular disease, unstable angina, or cardiac arrhythmia, other than supraventricular tachycardia (SVT)

20. Medically unstable hypertension

21. Current use of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, monoamine oxidase (MAO) inhibitors, tricyclic anti-depressants or other agents that could interfere with the treatment of anaphylaxis, in the opinion of the investigator

22. Unstable asthma within 3 months of randomization or symptomatic asthma on the day of vaccination, as assessed by the site investigator

23. Have past or current medical problems or findings from physical exam or laboratory testing not listed above, which in the opinion of the investigator, may pose additional risks from participation in the study or which may interfere with the ability to comply with study requirements --This includes individuals with underlying conditions or other medications that, in the opinion of the investigator, may increase risk in the event of an anaphylactic reaction or lead to complications following administration of epinephrine

Related Conditions & MeSH terms

• Allergic Reaction
• COVID-19
• Hypersensitivity
• Mast Cell Disorder
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

Biological:
• Moderna COVID-19 Vaccine
Intramuscular injection
• Pfizer-BioNTech COVID-19 Vaccine
Intramuscular injection
• Placebo
Intramuscular injection

Locations

Country	Name	City	State
United States	University of Michigan Health	Ann Arbor	Michigan
United States	Emory University School of Medicine, Emory Healthcare: Emory Clinic Allergy and Immunology	Atlanta	Georgia
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	North Carolina Translational and Clinical Sciences Institute-Clinical & Translational Research Center (CTRC) at the University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Virginia Health System: Department of Medicine, Division of Allergy and Immunology	Charlottesville	Virginia
United States	Sinus and Allergy Center of Northwestern University	Chicago	Illinois
United States	Cleveland Clinic, Allergy & Clinical Immunology	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	Henry Ford Hospital and Health System	Detroit	Michigan
United States	Penn State Health Allergy, Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor College of Medicine Medical Center	Houston	Texas
United States	University of Iowa Health Care	Iowa City	Iowa
United States	Arkansas Children's, University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	University of California, Los Angeles Medical Center	Los Angeles	California
United States	University of Wisconsin Asthma Allergy Pulmonary Research	Madison	Wisconsin
United States	University Health, University of Miami Health System	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Irving Medical Center	New York	New York
United States	Mount Sinai Hospital, Department of Medicine, Division of Clinical Immunology	New York	New York
United States	Virginia Commonwealth University, Department of Internal Medicine, Division of Rheumatology, Allergy & Immunology	Richmond	Virginia
United States	Rochester Regional Health	Rochester	New York
United States	Saint Louis University Care Center for Specialized Medicine	Saint Louis	Missouri
United States	NorthShore University HealthSystem, Dermatology Clinical Trials Unit	Skokie	Illinois
United States	Stanford Medicine, Sean N. Parker Center for Allergy & Asthma Research	Stanford	California
United States	University of South Florida Asthma Allergy and Immunology Clinical Research Unit	Tampa	Florida
United States	University of Arizona Health Sciences, College of Medicine Tucson, Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine	Tucson	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Immune Tolerance Network (ITN), Rho Federal Systems Division, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to Either Dose of Pfizer-BioNTech COVID-19 Vaccine.	Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.	Within the 90-minute post-vaccination observation period to either dose of the Pfizer-BioNTech COVID-19 Vaccine.
Primary	Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to Either Dose of the Moderna COVID-19 Vaccine.	Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.	Within the 90-minute post-vaccination observation period to either dose of the Moderna COVID-19 Vaccine.
Secondary	The Proportion of Participants Who Experienced a Severe (CoFAR Grade 3+) Systemic Allergic Reaction Within 90 Minutes Post-vaccination to Either Dose of the Pfizer-BioNTech COVID-19 Vaccine.	Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.	Within the 90-minute post-vaccination observation period to either dose of the Pfizer-BioNTech COVID-19 Vaccine.
Secondary	The Proportion of Participants Who Experienced a Severe (CoFAR Grade 3+) Systemic Allergic Reaction Within the 90-minute Post-vaccination Observation Period to Either Dose of the Moderna COVID-19 Vaccine.	Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.	Within the 90-minute post-vaccination observation period to either dose of the Moderna COVID-19 Vaccine.
Secondary	The Proportion of Participants Who Experienced an Anaphylactic Reaction Per Brighton Collaboration Criteria (Levels 1-3) Within 90 Minutes Post-vaccination to Either Dose of the Pfizer-BioNTech COVID-19 Vaccine.	Allergic reactions were graded using the Brighton Collaboration Criteria. The scale ranges from level 1 through 3. Level 1 represents the highest level of diagnostic certainty that a reported case is anaphylaxis, levels 2 and 3 represent successively lower levels of diagnostic certainty. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.	Within the 90-minute post-vaccination observation period to either dose of the Pfizer-BioNTech COVID-19 Vaccine.
Secondary	The Proportion of Participants Who Experienced an Anaphylactic Reaction Per Brighton Collaboration Criteria (Levels 1-3) Within 90 Minutes Post-vaccination to Either Dose of the Moderna COVID-19 Vaccine.	Allergic reactions were graded using the Brighton Collaboration Criteria. The scale ranges from level 1 through 3. Level 1 represents the highest level of diagnostic certainty that a reported case is anaphylaxis, levels 2 and 3 represent successively lower levels of diagnostic certainty. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.	Within the 90-minute post-vaccination observation period to either dose of the Moderna COVID-19 Vaccine.
Secondary	Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to the First Dose of the Pfizer-BioNTech COVID-19 Vaccine.	Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. The comparison is between the participants who received active vaccine as their first, fully blinded, injection (assigned to the Pfizer-BioNTech COVID-19 Vaccine arm) and participants who received their first active vaccine as their second injection (assigned to the Placebo + Pfizer-BioNTech COVID-19 Vaccine arm). Due to the design of the trial, participants would have understood that the second dose in any arm must be an active vaccination.	Within the 90-minute post-vaccination observation period to the first dose of the Pfizer-BioNTech COVID-19 Vaccine.
Secondary	Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to the First Dose of the Moderna COVID-19 Vaccine.	Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. The comparison is between the participants who received active vaccine as their first, fully blinded, injection (assigned to the Moderna COVID-19 Vaccine arm) and participants who received their first active vaccine as their second injection (assigned to the Placebo + Moderna COVID-19 Vaccine arm). Due to the design of the trial, participants would have understood that the second dose in any arm must be an active vaccination.	Within the 90-minute post-vaccination observation period to the first dose of the Moderna COVID-19 Vaccine.
Secondary	Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to the Second Dose of the Pfizer-BioNTech COVID-19 Vaccine.	Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. The comparison is between the participants who received the second active vaccine as their second injection (assigned to the Pfizer-BioNTech COVID-19 Vaccine arm) and participants who received the second active vaccine as their third injection (assigned to the Placebo + Pfizer-BioNTech COVID-19 Vaccine arm). This comparison is conditional on there being no systemic allergic reaction to the first dose.	Within the 90-minute post-vaccination observation period to the second dose of the Pfizer-BioNTech COVID-19 Vaccine.
Secondary	Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to the Second Dose of the Moderna COVID-19 Vaccine.	Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale is ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. The comparison is between the participants who received the second active vaccine as their second injection (assigned to the Moderna COVID-19 Vaccine arm) and participants who received the second active vaccine as their third injection (assigned to the Placebo + Moderna COVID-19 Vaccine arm). This comparison is conditional on there being no systemic allergic reaction to the first dose.	Within the 90-minute post-vaccination observation period to the second dose of the Moderna COVID-19 Vaccine.
Secondary	The Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to the First Dose, Adjusting for Placebo.	Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. The comparison is between participants who had placebo as their first injection (either vaccine) and participants who had Pfizer-BioNTech COVID-19 Vaccine as their first injection. The comparison only includes subjects in the HA/MCD cohort.	Within the 90-minute post-vaccination observation period to the first injection (placebo or active).
Secondary	The Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to the First Dose, Adjusting for Placebo.	Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale is ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. The comparison is between participants who had placebo as their first injection and participants who had Moderna COVID-19 Vaccine as their first injection. The comparison only includes subjects in the HA/MCD cohort.	Within the 90-minute post-vaccination observation period to the first injection.
Secondary	The Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+) Within 48-hours Post-vaccination to Either Dose of the Pfizer-BioNTech COVID-19 Vaccine.	Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.	After the 90 minute observation period to 48-hours post-vaccination to either dose of the Pfizer-BioNTech COVID-19 Vaccine.
Secondary	The Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+) Within 48-hours Post-vaccination to Either Dose of the Moderna COVID-19 Vaccine.	Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.	After the 90 minute observation period to 48-hours post-vaccination to either dose of the Moderna COVID-19 Vaccine.

External Links

•   Division of Allergy, Immunology, and Transplantation (DAIT)
•   National Institute of Allergy and Infectious Diseases (NIAID)
•   National Institutes of Health News Release Describing Study