COVID-19 vaccine ingredients can trigger allergic reactions, but officials say it’s rare – The Arizona Republic

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Amid growing reports of severe allergic reactions to COVID-19 vaccines, regulators are warning people with a history of such reactions to take precautions before they get their shots.

Experts say the number one suspect for these reactions is an ingredient commonly found in cosmetics, other medicine and laxatives called polyethylene glycol, or PEG. The Centers for Disease Control and Prevention says the reactions are still rare and investigations are ongoing.

The ingredient in question is used to stabilize current COVID-19 vaccines. But PEG has caused anaphylaxis, severe allergic reactions, in the past, said Ayrn O’Connor, a Banner Health physician.

“It’s pervasive,” O’Connor said. “Because it’s a common ingredient … that’s the one that’s the most suspicious, but we don’t have 100% confirmation.”

PEG is in both Pfizer’s and Moderna’s COVID-19 vaccines, which are currently the only ones with emergency use authorization from the Food and Drug Administration.

The rate of severe allergic reactions to the vaccines so far is a little higher than that of past vaccines, though that number could change in coming weeks.

The rate, at about 11 cases for every 1 million patients, is still well below 1% and means the vaccine is considered safe, O’Connor said.

Most of the other ingredients in the vaccine, some as common as table salt and sugar, are also found in a variety of other medications, foods or vaccines.

Another possible culprit behind anaphylaxis could be ingredients called lipids. Lipids don’t dissolve in water and can include fats, waxes and oils. Certain lipids are sometimes used as ingredients in vitamin supplements to help the body absorb the nutrients.

Rick Kennedy, co-director of the Mayo Clinic Vaccine Research Group, describes lipids as drops of oil that encase the mRNA, or genetic material, inside both vaccines. They protect the mRNA and help it slip through a cell membrane into a cell.

PEG is one type of lipid, but both vaccines also contain others. And while ingredients like sugar and salt are commonly found in other vaccines, lipids are not, and experience using them may be limited.

“These lipids, their purpose is really to get the mRNA into a cell, and we’ve never had mRNA vaccines,” Kennedy said. “It’s unlikely that anybody’s allergic to the salts or the sugars, but it could be any of these other lipids.”

Most people won’t have reactions to these lipids, but they may experience some side effects to the vaccine. Commonly reported side effects such as fatigue, muscle aches or fever are not usually signs of an allergic reaction, according to medical experts, but are actually signs the immune system is fighting off the novel coronavirus and the vaccine is working.

Risk factors for severe allergic reaction

Miloni Patel, a public health nurse, prepares a COVID-19 vaccination at Hayden High School in Winkelman, Ariz. on Jan. 21, 2021.

If people have had allergic reactions to other vaccines in the past, health care experts recommend they talk with a doctor before getting a COVID-19 vaccine.

“It doesn’t mean that they can’t have it,” O’Connor said. “It means that they should probably have precautions taken.”

When someone has a severe allergic reaction, it is often linked to a type of antibody made by the immune system called an IgE antibody, according to Miriam Anand, an allergist and president-elect of the Arizona Medical Association.

The first time the immune system encounters something foreign, it learns how to fight it using different types of antibodies. But if it creates too many IgE antibodies, it can cause an immune system overreaction.

IgE antibodies are usually found in low levels in the blood and can have powerful downstream effects. They can trigger other types of immune cells that act as “bombers” against a foreign substance. One example is a mast cell, which Kennedy described as “chock full of cytokines,” or proteins that can trigger inflammation.

Allergic, inflammatory responses can cause rashes, swelling, hives and discomfort. But in severe cases, these immune system overreactions can cause blood pressure to drop, systemic inflammation, throat swelling and other life-threatening symptoms.

Since PEG is a fairly large molecule, Kennedy said the immune system can recognize it and create antibodies against it, further strengthening suspicion that PEG could be the problematic ingredient in COVID-19 vaccines.

If someone has had a past reaction to PEG, they’re likely to react to PEG again in the future. The same rule applies to molecules that aren’t PEG but that look similar.

One type of molecule that looks similar are polysorbates, oily liquids often found in pharmaceutical products, cosmetics and foods such as ice cream. Anand said many vaccines, such as the seasonal influenza vaccine, contain polysorbates.

“So if they already had an anaphylactic reaction to a vaccine that contained polysorbates, that means they’re already making antibodies against that and therefore they could be at higher risk,” Anand said.

People with a history of reactions to medications or vaccines should review COVID-19 vaccine ingredients with an allergist or doctor to determine their risks, she added.

Allergists can test directly for ingredient reactions by pricking a patient’s skin with the vaccine itself or with certain ingredients to see if hives form. It’s hard to test with the Pfizer or Moderna vaccine due to short supply and cold storage requirements, but Anand said doctors could test laxatives containing PEG on a patient’s skin to check for allergies.

People with a history of food or seasonal allergies are still considered to be at low-risk for an allergic reaction to the COVID-19 vaccine, Anand said.

The Moderna and Pfizer vaccines don’t contain other ingredients that can cause allergic reactions, such as eggs, gelatin or latex, but it’s still unclear what ingredients will be in future COVID-19 vaccines currently under development by companies like Johnson & Johnson and Novavax. The AstraZeneca vaccine does contain polysorbate.

Younger patients may be more likely to experience anaphylaxis. The average age of those who have experienced severe allergic reactions so far is 40, according to a recent report by the CDC. This is because they have stronger, more robust immune systems, O’Connor said, and means younger patients are more likely to experience non-allergic side effects as well.

The Moderna and Pfizer vaccines have some similar ingredients, including polyethylene glycol.

mRNA causes common side effects.

All vaccines work by stimulating the immune system and training it to recognize and fight a particular substance again in the future. There are two stages of an immune system response: the innate immune response and the adaptive immune response.

The innate immune response is the body’s immediate reaction when it recognizes something foreign. Certain receptors on cells can spot common structural patterns found in bacterias and viruses, which is what triggers the innate immune response.

As part of its innate response, the immune system uses cytokines to trigger inflammation, raise body temperature or cause blood to leak more easily out of blood vessels.

Typically, these are good responses, because they help fight foreign substances, but it’s important not to over-stimulate the innate immune system response. The risk, Kennedy said, is more severe side effects.

In the case of the Moderna and Pfizer vaccines, the body recognizes mRNA as foreign. mRNA is the active ingredient in the vaccine and gives cells a blueprint to make the spikes on the outside of the virus. The virus uses the spikes to enter and infect cells and immune system antibodies neutralize the virus by binding to the spikes.

Kennedy said the mRNA in the vaccines has been slightly modified, probably “so that it does not provoke an immediate innate immune response.”

The body then has more time to learn what the spikes on the virus look like and can mount a better immune response in the future. Otherwise, the body might destroy the mRNA before creating long-lasting antibodies for the spike.

Kennedy said the modifications likely helped blunt side effects from that innate response to avoid immune system overreactions as well.

Typically, side effects from the first COVID-19 vaccine shot are minimal, most commonly including a sore arm, but after the second shot, when the body is exposed to even more mRNA and spikes, it mounts a stronger innate response.

The syringes with COVID-19 vaccines sit at the ready to be administered in a drive-thru vaccination clinic at Chandler Gilbert Community College in Chandler, Ariz. on Dec. 21, 2020.

Side effects usually kick in about 12 hours after the shot, according to O’Connor, but fade within 24 to 36 hours. The side effects are usually mild and transient.

A sore arm at the injection site is the most common side effect from the vaccines. Symptoms of either headaches or fatigue occur in roughly half of patients, body aches are less common and fewer than 14 percent of vaccine recipients experience fever, according to O’Connor.

“It’s a sign the immune system is doing what it’s supposed to do, mounting a response,” she said.

A lack of side effects doesn’t mean the innate immune response isn’t working, and why some people show reactions and some don’t is still a mystery.

The stronger a person’s innate immune response is, the stronger their adaptive, or long term, immune response will be. Adaptive immune responses use specialized cells and antibodies trained to target specific substances — in this case, the novel coronavirus spikes.

But training these cells and antibodies can take longer, meaning the lasting COVID-19 protection provided by the adaptive immune response doesn’t kick in right away. That’s why full protection from the COVID-19 vaccines doesn’t start until about one or two weeks after receiving the second booster shot.

Vaccine unlikely to have long term effects

Melissa DeFelice holds a syringe with the COVID-19 vaccine, waiting to administer the vaccine to frontline healthcare workers at a drive-thru clinic at Chandler Gilbert Community College in Chandler, Ariz. on Dec. 21, 2020.

Some people are concerned about COVID-19 vaccines due to their fast-paced development, but experts say they aren’t worried. The vaccine safety data looks good, ingredients in the vaccines are commonly found in other medications or food and long-term vaccine side effects are rare.

“Vaccines … have the greatest safety track record of any medical intervention in the history of medicine,” O’Connor said. “They are the safest therapeutic option of any medication out there.”

The mRNA doesn’t last long in the body and is typically destroyed within minutes or hours, Kennedy said, so he believes that there should be no long term vaccine side effects.

Though health care professionals didn’t see any reasons to be worried about long term side effects, they acknowledged it’s not possible to be absolutely certain at this point, which is why experts are continuously tracking vaccine data.

The other unclear aspect is how long protection against COVID-19 will last. Health care professionals said patients who have already had COVID-19 should still get vaccinated because there’s a possibility they could get reinfected. Reinfections are rare, but the immune protection against COVID-19 may wane over time.

O’Connor cautioned that patients should ensure they are no longer actively sick with COVID-19 before getting vaccinated.

“Our immune system is already pretty busy and we don’t want to overload it,” she said.

She recommended that anyone with an active or recent COVID-19 infection and those with long lasting symptoms should talk with their doctors.

Once vaccinated, patients should continue to take public health precautions like wearing a mask and staying six feet apart, because there’s no data yet on whether vaccines can prevent a person from spreading the virus to others.

This will likely be less of an issue once a population reaches herd immunity, which is established once enough people have been vaccinated. Even with side effects and allergic responses, O’Connor believes the benefits of the vaccine far outweigh the risks.

““I hope it’s the beginning of the end of the pandemic but we all have to get vaccinated,” she said. “You couldn’t get a shot in my arm fast enough.”

Moderna Ingredients

Active ingredient: mRNA, or genetic blueprint to create the virus’s spike.

Salts (helps the vaccine match the pH, or acidity, of blood and muscle cells so that they aren’t damaged by the vaccine): 

Sodium acetate

Sugar (helps stabilize the virus and prevents clumping):

Sucrose.

Other ingredients that help maintain the right pH for the vaccine:

Acetic acid (a substance found in vinegar), tromethamine and tromethamine hydrochloride

A list of Moderna ingredients can be found on the FDA website.

Pfizer Ingredients

Active ingredient: mRNA, or genetic blueprint to create the virus’s spike.

Salts (helps the vaccine match the pH, or acidity, of blood and muscle cells so that they aren’t damaged by the vaccine):

Potassium chloride, monobasic potassium phosphate, dibasic sodium phosphate dihydrate and sodium chloride.

Sugar (helps stabilize the virus and prevents clumping):

Sucrose.

A list of Pfizer ingredients can be found on the FDA website.

Amanda Morris covers all things bioscience, which includes health care, technology, new research and the environment. Send her tips, story ideas, or dog memes at [email protected] and follow her on Twitter @amandamomorris for the latest bioscience updates.

Independent coverage of bioscience in Arizona is supported by a grant from the Flinn Foundation. 

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