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):

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