The recent approval of two novel messenger RNA (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines by various regulatory agencies have provided hope that we may finally be able to end the pandemic that has caused over 100 million infections and claimed more than 2.3 million lives worldwide.
The first vaccine approved to prevent COVID-19 (Pfizer-BioNTech) began in the United Kingdom in December 2020. Within days, there were reports of two or possibly three anaphylactic reactions following vaccination. The same vaccine was subsequently given emergency use authorization (EUA) by the United States Food and Drug Administration (FDA), and again, within days, there were reports of at least two anaphylactic reactions. A second mRNA vaccine (Moderna) has also now been approved.
A commentary by John M. Kelso, Division of Allergy, Asthma and Immunology, Scripps Clinic, published in the latest issue of the journal Vaccines, discusses anaphylactic reactions to these novel mRNA SARS-CoV-2/COVID-19 vaccines.
Anaphylaxis is a multi-organ event that occurs because of the release of histamines and other mediators from mast cell granules and can be fatal. Prior exposure to an allergen can lead to the formation of IgE antibodies, which coat mast cells. When a person reencounters the allergen, these antibodies are released into the tissues and blood.
Mast cells are mostly found in the skin and the respiratory and gastrointestinal tracts. Symptoms of anaphylactic reactions include flushing of the skin, coughing, wheezing, abdominal pain, and nausea. The reaction can be fatal because of asphyxiation in the upper airway, severe bronchospasm, or extremely low blood pressure.
In general, anaphylactic reactions to vaccinations are very rare, occurring at a rate of about 1 per million. But, the reports on COVID-19 vaccines indicate these reactions have a higher than normal rate. Ongoing investigations by manufacturers and regulatory agencies are trying to determine if these are indeed allergic reactions and determining what component of the vaccine is the allergen.
Determining anaphylactic reactions to vaccines
This will first require checking if the timing and symptoms are consistent with a diagnosis for an anaphylactic reaction. IgE-mediated reactions typically occur within minutes of exposure to the allergen, and hence, any allergic reaction to the vaccine should be evident soon after vaccination.
If the symptoms after vaccination are consistent with an anaphylactic reaction, the next step will be checking for IgE antibodies. Since the approved vaccines are new, it is unlikely the patients were exposed before to form IgE antibodies, but they may have been sensitized to some component of the vaccine.
The vaccines are modified mRNA encoding the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A component of the vaccines, polyethylene glycol (PEG), has been reported to cause IgE-mediated reactions and is considered a possible allergen. PEG is widely used in several medicines, cosmetics, and foods, and such exposure could have sensitized some patients. Thus, these vaccines could be unsuitable for those rare individuals with PEG allergy.
Vaccines should be administered in a setting that allows observation after the injection to allow for appropriate treatment of any allergic reaction, such as administering epinephrine. After that, testing blood samples for mast cell tryptase can allow further diagnosis, a high level indicating an allergic reaction, although normal levels do not exclude it.
Investigating possible allergens
After the reports of anaphylactic reaction to the Pfizer vaccine, the UK Medicines and Healthcare products Regulatory Agency (MHRA) issued guidance that any persons with known allergic reactions to any vaccine, medicines, or food should not be given the vaccine. In the United States, the Centers for Disease Control (CDC) has said that any person with a history of a severe allergic reaction should be observed for 30 minutes after vaccination and others for 15 minutes.
Although PEG is a possible suspect, there could be other allergens. But, because PEG allergy is very rare and people who could be allergic to it may have been sensitized to it without having any reaction, it may be challenging to identify who may be allergic to the vaccine beforehand, if PEG is indeed the allergen.
Patients who have had an anaphylactic reaction to the first dose of a vaccine should not receive the second dose. Other vaccines being developed are different from the mRNA vaccines, and that such patients may be able to receive a different vaccine.
“While anaphylaxis is a potentially life-threatening event, it is almost always successfully treated, and its risk must be weighed against leaving patients unvaccinated and therefore susceptible to a potentially life-threatening disease, COVID-19,” writes the author.
Investigations into the seeming anaphylactic reactions should proceed quickly and thoroughly to narrow down the patients who may suffer a severe reaction and not eliminate those who will not have any reaction and could be protected from COVID-19.