Dr. Pedro Morais Silva

Allergist-Immunologist

Allergy to covid-19 vaccines
Some questions and answers

HPA Magazine 16

Vaccines against the SARS-CoV-2 virus are currently the most promising developments to control the COVID-19 pandemic.
However, following news of severe allergic reactions after vaccination, it is understandable that the public, including health professionals have some questions about their safety.
The main objective of this article is to try to clarify some of the most frequent doubts, in light of current knowledge (May 2021), in order to promote a quick, effective and safe vaccination campaign.
As information is constantly being updated, we recommend the consultation of the guidelines of the Direção-Geral de Saúde (DGS) [covid19.min-saude.pt/normas] or of the Portuguese Society of Allergology and Clinical Immunology [spaic.pt].

/ WHICH VACCINES ARE CURRENTLY AVAILABLE IN PORTUGAL? ARE THEY ALL EFFECTIVE AND SAFE?
The vaccines that have been approved and are currently available in Portugal are, Pfizer/BioNTech, Moderna, Johnson & Johnson and AstraZeneca. These vaccines are different in their mechanism, but all have shown to be safe and effective. The vaccines produced by Pfizer/BioNTech and Moderna use a fragment of the genetic code of SARS-CoV-2, delivered in an ultrasmall droplet of fat, which encodes one of the main proteins of the virus, responsible for entering human cells. The immune system recognizes that the protein is foreign and that it contains a potential aggressor for the human body. Consequently, white blood cells that have been educated to fight viruses, produce specific antibodies against the virus.
Vaccines produced by AstraZeneca and Johnson & Johnson share a similar mechanism, using a modified adenovirus as a carrier for the genetic code of the SARS-CoV-2 virus protein. This modified virus is not replicative, so it does not cause an infection and is eliminated after delivering the protein. From an immunological point of view, the vehicle is different, but the protein delivered to the immune system is the same in all 4 vaccines. There are slight differences in the percentage effectiveness of each vaccine, but all have been shown to be effective and safe.
In Portugal, all vaccines are provided free of charge. However, it is not possible for each patient to choose which vaccine they will receive.
/ WHAT ARE THE VACCINATION PRIORITY GROUPS?
Given vaccine scarcity and risk stratification, priority groups were defined:
Phase 1: health professionals, all people over the age of 80 and people over the age of 50 with serious illnesses such as heart failure, coronary heart disease or COPD under ventilatory support and/or long-term oxygen therapy;
Phase 2: all people over the age of 16, decreasing according to age groups, with priority given to those with risk factors, such as diabetes, active malignant neoplasia, chronic kidney disease, liver failure, obesity, among others.
/ AS FAR AS THE RISK OF DEVELOPING AN ALLERGIC REACTION IS CONCERNED, WHAT ARE THE CURRENT CONTRAINDICATIONS FOR ADMINISTERING THE CURRENTLY AVAILABLE SARS-COV-2 VACCINES?
According to the current DGS Clinical Guidance Standards, the following are considered contraindications:
a) history of known allergy to one of the excipients of the vaccine to be administered; 
or
b) history of anaphylaxis to a previous vaccine against SARS-CoV-2 virus.
These patients must be referred urgently to an Immunoallergologist, for an evaluation, stratification of risk and the study of a possible alternative.
In addition, also considered a contraindication are patients with a previous history of:
a) anaphylactic reactions to other vaccines (non-SARS-CoV-2);
b) patients with a history of idiopathic anaphylaxis;
c) patients with confirmed allergy to excipients (even if not present in SARS-CoV-2 vaccines);
d) patients with systemic mastocytosis or mast cell proliferative diseases.

/ ARE ALLERGIC REACTIONS TO COVID-19 VACCINES COMMON?
No. These are estimated to occur in less than 1 in 10,000 administrations. However, as with any other medicine, vaccines can trigger unwanted effects that are sometimes incorrectly interpreted as an allergy. The most frequent adverse effects include: 
a) Reactions on the injection site.
b) Headache, muscle or joint pain, fever, tiredness, nausea, and general malaise. None of these symptoms are due to an allergic reaction and usually disappear spontaneously within 3 days.

/ WHAT APPEARS TO BE THE PERCENTAGE OF PATIENTS WHO EXPERIENCE SEVERE ALLERGIC REACTIONS TO VACCINES?
Serious allergic reactions to vaccines are, in general, very rare. It is estimated that they occur at a rate of approximately 1.31 per 1,000,000 vaccines administered. T
he number of reactions associated with the Pfizer/BioNTech and Moderna vaccines initially appeared to be higher than with the others, but the cumulative data did not find statistically significant differences.

/ WHAT CURRENT PRECAUTIONS EXIST TO SAFEGUARD POSSIBLE ALLERGIC REACTIONS TO VACCINES?
Vaccination campaigns take place in locations with appropriate medical equipment for treatment of severe allergic reactions, including anaphylaxis. 
Since most post-vaccination anaphylaxis occur within the first 15 minutes, all patients remain under observation for 30 minutes after administration. Patients at high risk of adverse reactions receive their vaccine in a hospital setting, under Immunoallergology guidance.

 CAN PATIENTS WITH SEVERE FOOD ALLERGIES BE VACCINATED?
Yes. After reviewing cases of allergies related to the administration of SARS-CoV-2 virus vaccine, no relationship with food allergy was identified.

/ SOME VACCINES ARE CONTRAINDICATED FOR PATIENTS WITH EGG ALLERGY. DO THESE VACCINES CONTAIN EGG PROTEINS?
No. Pfizer/BioNTech, AstraZeneca, Johnson & Johnson and Moderna vaccines do not contain egg proteins.

/ CAN PATIENTS WHO ARE ALLERGIC TO MITES OR POLLENS RECEIVE THE VACCINE AGAINST THE SARS-COV-2 VIRUS? AND CAN PATIENTS WHO ARE UNDERGOING ALLERGEN IMMUNOTHERAPY (“ALLERGY SHOTS”) BE VACCINATED?
Yes. Allergy to respiratory allergens is not a contraindication for any of the currently available vaccines. Likewise, patients undergoing immunotherapy with aeroallergens can be vaccinated. An interval of at least one week between the SARS-CoV-2 vaccine and the administration of immunotherapy is necessary.

/ WHAT ABOUT AN ALLERGY TO POLYETHYLENE GLYCOL (PEG) AND POLYSORBATE 80?
Pfizer/BioNTech and Moderna mRNA vaccines contain PEG. PEGs exist in different molecular weights (also called macrogols) and are excipients often present in medication and cosmetics, so it is likely that most of the population will have had contact with these substances throughout their lives. It is suspected that some allergic reactions that have occurred are due to these compounds, but further studies will be needed to clarify this relationship. Allergy to PEG is very rare, but it is a contraindication to mRNA vaccine use.
AstraZeneca and Johnson & Johnson vaccines do not contain PEG, but a similar excipient called polysorbate 80. Allergy to polysorbate 80 appears, however, to be rarer than PEG. Other vaccines, such as the flu vaccine, contain polysorbate 80.
Allergy to excipients should be suspected especially in patients with episodes of allergic reactions (especially anaphylaxis) with multiple drugs that are not chemically related to each other.

/ ARE PATIENTS WITH ASTHMA AT HIGHER RISK OF HAVING A REACTION TO A VACCINE ?
No. However, as with other vaccines, it is recommended that asthma is controlled on the day of vaccination. 

/ CAN PATIENTS WITH A HISTORY OF ANAPHYLAXIS TO BEE OR WASP VENOM, RECEIVE THE VACCINE?
Yes. Insect poison allergy is not a contraindication to the currently available vaccines. However, a disease associated with anaphylaxis to poisons, systemic mastocytosis, is an indication for the administration of the vaccine in a hospital environment.

/ CAN PATIENTS WHO UNDERWENT HYALURONIC ACID COSMETIC FILLERS BE VACCINATED?
There are a few reports of patients who after being vaccinated, experienced oedema where hyaluronic acid or calcium hydroxylapatite was administered. The reported reactions occurred with the Moderna vaccine and were not considered serious. They do not appear to have occurred due to hypersensitivity to any of the compounds involved. It is currently recommended by the American Society for Surgical Dermatology that there be a 3-week gap between cosmetic filler procedures and the administration of the SARS-CoV-2 vaccine.

/ CAN PATIENTS WITH COMPROMISED IMMUNITY RECEIVE THE VACCINE?
mRNA and adenovirus vector vaccines are not live vaccines and cannot cause infection. For this reason, they are globally considered safe for administration in immunocompromised patients. However, depending on the underlying pathology, some patients may have an impaired immune memory response to vaccines.

/ SINCE MORE SARS-COV-2 VACCINES ARE CURRENTLY IN DEVELOPMENT, DOES IT MAKE SENSE TO WAIT FOR A NEW VACCINE WITH LESS ALLERGENICITY?
There are currently several vaccines being developed. Each vaccine is different and various administration techniques are being tested. However, ingredients of future vaccines are not yet known and there is no reason to believe that they will be any more (or less) safer from an allergy point of view, than those currently available. It is therefore not recommended to postpone vaccination for any allergic patient unless they have the aforementioned contraindications.

Usefull links and helpfull Support 
•CDC. COVID-19: J&J/Janssen update, Maio 16, 2021. on: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/JJUpdate.html. Acedido em maio 2021.
•CDC. Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine – United States, December 21, 2020 – January 10, 2021. On:https://www.cdc.gov/mmwr/volumes/70/wr/mm7004e1.htm. Acedido em maio 2021.
•DGS. Covid-19. Frequent questions on: https://covid19.min-saude.pt/category/perguntas-frequentes/ Acedido em maio 2021.
•EMA. COVID-19 vaccine AstraZeneca: benefits till outweigh the risks despite possible link to rare blood clots with low platelets. On: https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazeneca-benefits-still-outweigh-risks-despite-possible-link-rare-blood-clots. Acedido em maio 2021.
•Greinacher A, et al. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 vaccination. NEJM 2021:doi 10.1056/NEJMoa2104840.
•IPCRG What are the safety concerns and what are the serious side effects reported with existing SARS-CoV-2 vaccines? On: https://www.ipcrg.org/resources/search-resources/what-are-the-safety-concerns-and-what-are-the-serious-side-effects
•Remmel A. COVID vaccines and safety: That the research says. Nature 2021;590:538-40.
•SPAIC: Vacinação contra a COVID-19. Disponível em: https://www.spaic.pt/noticias/vacinaocovid19. Acedido em maio 2021.
•WHO Team. How to monitor and report COVID-19 vaccine side effects. 15 March 2021. Disponível em: https://www.who.int/publications/m/item/how-to-monitor-and-report-covid-19-vaccine-side-effects. Acedido em maio 2021.
•Yuan P, et al. Safety, tolerability, and immunogenicity of COVID-19 vaccines: A systematic review and meta-analysis. Lancet 2021. On: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3746259. Acedido em março 2021.