Mast cell disorders and the COVID-19 vaccine

1) What is mast cell disorder?

Mast cells play a significant role in our bodies’ immune response, but they can also cause allergic reactions or anaphylaxis. Mast cell disorders are conditions caused by an increased number of mast cells and/or hyperactive mast cells in the body. These disorders can vary in severity, but common symptoms include severe reactions to foods, medicines, or insect stings. Mast cell disorders can be broken up into three major forms: mastocytosis, mast cell activation syndrome (MCAS) and Hereditary Alpha tryptasemia (HAT).

2) How is mast cell disorder connected to Covid vaccine allergic reactions?

It is unclear whether mast call disorders are connected to covid vaccine allergic reactions. The NIH is conducting a multi-site national clinical study to further evaluate COVID-19 vaccine allergic reactions including risk factors for allergic reactions to these vaccines.

3) Who is susceptible to such reactions?

The data has been conflicting regarding risk factors for allergic reactions to Covid-19 vaccines. Some patients who have reactions appear to have a history of atopy/allergic diseases including eczema, asthma, and allergies while others do not have this history.

4) How likely is the COVID vaccine to cause such reactions?

Allergic reactions to the COVID-19 vaccine are rare. As more and more people are vaccinated, the numbers are constantly changing. On average, reactions to the Moderna vaccine occur at a rate of 2.5 cases per 1 million doses, at 11.1 cases per million doses to the Pfizer-BioNTech vaccine, and fewer than 0.5 cases per 1 million doses to the Janssen vaccine.

5) How can advanced blood testing help identify allergen triggers for a more targeted treatment plan?

There is no commercially available testing to evaluate for allergens within the COVID-19 vaccine. The suspected allergen in the COVID-19 is PEG or polysorbate but additional studies are needed to confirm the culprit allergen(s).

6) How does tryptase help clinicians determine mast cell activation during a severe allergic reaction?

Tryptase is an enzyme released from basophils and activated mast cells during normal and abnormal immune responses. Mast cells contain approximately 500-fold more tryptase than basophils, so serum tryptase concentration can indicate mast cell activity. A clinical event would result in a brief rise in serum tryptase concentration, whereas a patient with a mast cell disorder would show a high level of serum tryptase concentration over a prolonged period and a higher count of mast cells in the body. 

7) When might it be necessary to take a blood test to measure increased levels of tryptase?

While there is no lab test that can definitely determine the cause of a severe allergic reaction (e.g., anaphylaxis) following COVID-19 vaccination, tryptase can be used to help characterise a severe allergic reaction.

Patients who repeatedly show symptoms of mast cell activation, such as anaphylaxis, should be tested. Because tryptase is released during anaphylaxis, clinicians should aim to collect tryptase between 30 to 90 minutes after the start of the reaction, but patients can be tested for elevated tryptase up to six hours after the start of a reaction.

8) Why do adverse reactions to COVID vaccines occur to some people and not others?

It is unclear why adverse reactions to COVID-19 vaccines occur in some people and not others and that is why the NIH is conducting a large national clinical trial to try to understand the risk factors for allergic reactions to the COVID-19 vaccine. The study team will enroll 3,400 participants, 60% of which having either a history of severe allergic reactions or a diagnosis of a mast cell disorder, and the other 40%, will not. The findings of the Phase 2 trial, called Systemic Allergic Reactions to SARS-CoV-2 Vaccination, will provide more clarity around the risks and benefits of receiving the COVID-19 vaccines, particularly for people who have allergies or mast cell disorder.

9) Is there any connection between mast cell disorders and susceptibility to vaccine side effects other than an allergic reaction?

Although the studies are limited, there is no well established connection between mast cell disorders and susceptibility to vaccine side effects other than allergic reactions.

Author: Dr Lakiea Wright is a practicing physician at Brigham and Women's Hospital in Boston and Medical Director at Thermo Fisher Scientific. She is a Board-Certified Physician in Internal Medicine and Allergy and Immunology, providing care for pediatric and adult populations