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

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):

• Able to understand and provide informed consent
• 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)
• 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

• 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:

• 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
• 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
• History of documented, immediate allergic reactions to 2 or more unrelated drugs within the last 15 years
• 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
• History of physician-diagnosed idiopathic anaphylaxis requiring epinephrine or an Emergency Department visit in the last 15 years
• 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:

• No history of allergic asthma or atopic dermatitis within the last 10 years
• No history of chronic spontaneous urticaria, or angioedema
• No history of allergic reactions to foods or insect venoms
• No history of allergic reactions to drugs or vaccines
• No history of anaphylaxis
• 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 enrollme