The First 30 Minutes: Anaphylaxis After COVID Vaccination

Sandra Adamson Fryhofer, MD


January 27, 2021

Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

This transcript has been edited for clarity.

We now have two mRNA COVID vaccines.

For both, a two-dose series of the same vaccine is more than 90% effective. Pfizer/ BioNTech's mRNA COVID vaccine is FDA authorized for those 16 and older. Moderna's mRNA COVID vaccine is authorized for those 18 and older.

The phase 3 studies on both vaccines are huge: nearly 44,000 for the Pfizer vaccine and 30,000 participants for the Moderna vaccine. In these large trials, no cases of anaphylaxis were observed following administration of either vaccine. But remember the headlines about severe allergic reactions to Pfizer's vaccine in the UK? We're seeing them here in the US, too.

A new study in MMWR reports on 21 cases of anaphylaxis in the first 1.9 million Pfizer doses administered in the United States. This translates to 11.1 cases of anaphylaxis per 1 million COVID vaccine doses. To put this into context, for flu vaccination, the anaphylaxis rate is only 1.3 per million. Moderna's vaccine has been linked to anaphylaxis, too.

CDC's Dr Nancy Messonnier says that "even at 11 cases per million doses administered, it's a very safe vaccine... it's still a good value proposition for someone to get vaccinated."

Here's a head-to-head comparison of mRNA vaccine components. The ingredients for each are a little different (Table 1).

Table 1. Ingredients of the mRNA COVID-19 Vaccines

Table 1. Download PDF here

  • Each vaccine has four lipid ingredients that make up its protective lipid nanoparticle, forming a cushion around fragile mRNA to protect it and give it time to do its job.

  • Each vaccine also contains an array of salts, sugars, and buffers. Sugars keep the vaccine from clumping in the vial.

  • Neither vaccine contains eggs, gelatin, latex, or preservatives. Vaccine vial stoppers don't contain latex either.

  • Both vaccines contain polyethylene glycol (PEG).

Precautions and Contraindications

Here is CDC's guidance on COVID vaccines for patients with a history of allergies. This color-coded table provides a nice, quick-look summary (Table 2).

Table 2. Triage for mRNA COVID-19 Vaccination

Table 1. Download PDF here

The contraindications are in the red column. mRNA vaccines are contraindicated if the patient has a history of a severe allergic reaction, such as anaphylaxis, to a previous dose of mRNA COVID vaccine or to any of its components, including PEG.

The vaccines are also contraindicated if the patient is allergic to polysorbate, which is not a vaccine ingredient but is known to cause cross-reactive hypersensitivity with PEG.

What do mRNA vaccines have in common with the laxative Miralax and the colonoscopy preps GoLYTELY, CoLyte, and MoviPrep? They all contain PEG. If your patient has had an allergic reaction to a coloscopy prep containing PEG in the past, this is a contraindication to getting mRNA vaccine — unless they are cleared for vaccination by an allergist. That's current CDC guidance.

Precautions are in the yellow column. History of an immediate allergic reaction to any other vaccine or injectable therapy is a precaution for vaccination at this time. An immediate allergic reaction includes symptoms such as urticaria, angioedema, respiratory distress, or anaphylaxis within 4 hours following administration. "Injectable" is the key word here. It is a precaution, not a contraindication.

Those with a history of immediate allergic reaction to any other vaccine or injectable therapy would need to be evaluated and cleared by an allergist before being vaccinated. And any patient who has had an immediate allergic reaction to the first mRNA vaccine dose should not get a second dose.

These precautions do not apply to allergic reactions to foods, pet dander, venom, oral medications, latex, egg, or gelatin. Even with a history of these allergies, you can proceed with vaccination.


All patients should be observed after vaccination. Patients with precautions or any history of anaphylaxis to anything should sit and be observed for 30 minutes after vaccination. Everyone has to sit for at least 15 minutes after being vaccinated. CDC found that 71% of persons who experienced anaphylaxis showed symptoms within 15 minutes after vaccine administration.

CDC also has a helpful list of recommended medications, including epinephrine and antihistamines, and other supplies to have on hand at COVID vaccination sites (Table 3).

Table 3. Medications and Supplies for Management of Anaphylaxis

Table 1. Download PDF here

CDC does not recommend routine premedication with antihistamines for fear that it could mask skin reactions which could delay diagnosis and subsequent management of anaphylaxis. Except for pregnant women, CDC also does not recommend routine prophylactic NSAIDs or acetaminophen due to a lack of information on their impact on vaccine-induced antibody response.

These vaccines are reactogenic, so vaccine recipients can expect to have some symptoms, such as mild to moderate local and systemic reactions (pain, swelling, redness at the injection site) as well as localized axillary adenopathy on the same side as the vaccinated arm. Expect fever, fatigue, headache, chills, muscle aches, and joint aches.

These are not allergic reactions. Tell vaccine recipients to think of these symptoms as a sign that the vaccine is working. Most symptoms occur in the first 3 days after vaccination. Reactions are more intense after the second dose. Symptoms are also worse in younger as compared with older persons. The good news is that symptoms seem to resolve within 1-3 days.

Some of these vaccine reactions are the same as COVID symptoms. COVID may have to be ruled out, especially among healthcare providers who receive the vaccine. CDC has put together a toolkit for healthcare providers to help them decide whether their symptoms are due to COVID or just a side effect of vaccination.

CDC continues to update guidance with new information, so check their website regularly.

For Medicine Matters, I'm Dr Sandra Fryhofer.

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