With millions more healthcare workers and the general public slated to be immunized for COVID-19, researchers report that the Pfizer SARS-CoV-2 mRNA vaccine is causing anaphylactic shock reactions at 10 times the rate of typical vaccines.

In a published review of the issue, researchers reported that “in the United States after vaccination of almost 2 million healthcare workers … the incidence of anaphylaxis associated with the Pfizer SARS-CoV-2 mRNA vaccine appears to be approximately 10 times as high as the incidence reported with all previous vaccines, at approximately one in 100,000, as compared to one in 1,000,000.”1

With many more vaccines expected to come on the market in 2021, there are open questions whether such severe reactions will occur with other formulations.

“Acute allergic reactions after vaccination might be caused by the vaccine antigen, residual nonhuman protein, or preservatives and stabilizers in the vaccine formulation, also known as excipients,” the authors noted.

As of a Jan. 6, 2021, the Centers for Disease Control and Prevention (CDC) reported a total of 29 cases of anaphylactic shock following vaccination, but had detailed information and total immunization numbers on only 21 of those. No deaths were reported, but four patients were hospitalized, including three in intensive care. Another 17 were treated in an emergency department.

From Dec. 14 to Dec. 23, 2020, vaccine surveillance systems picked up 21 cases of anaphylaxis after administration of a reported 1,893,360 first doses of the Pfizer-BioNTech COVID-19 vaccine, the CDC reports.2 That comes to an allergic shock rate of 11.1 cases per million doses. Overall, 71% of the reactions occurred within 15 minutes of vaccination.

“The rate of anaphylaxis for flu vaccine is 1.3 per one million doses administered,” Nancy Messonnier, MD, director of CDC’s national center for immunization and respiratory diseases, said at a Jan. 6, 2021, press conference. “The anaphylaxis rate for COVID-19 vaccines may seem high compared to flu vaccines, but I want to reassure you this is still a rare outcome. This means that right now the known and potential benefits of the current COVID-19 vaccines outweigh the known and potential risks of getting COVID-19. ”

The median age of persons with anaphylaxis was 40 years, with a range of 27 to 60 years of age. Nineteen (90%) of the cases occurred in females. “In 19 of 21 reports, patients were treated with epinephrine as part of therapy; one patient received subcutaneous epinephrine and the remaining 18 were confirmed or presumed to have received intramuscular epinephrine,” the CDC reported.

Overall, 17 patients had a documented history of allergies or allergic reactions, including to drugs or medical products, foods, and insect stings, he said. No geographic clusters of anaphylaxis cases were observed, and the cases occurred after receipt of doses from multiple vaccine lots, Messonnier said. 

“Anyone who has an immediate or allergic reaction to the first dose should not receive the second dose,” she said. “Anyone with a history of an immediate allergic reaction to injectable vaccine and people with a history of anaphylaxis due to any cause should be observed for 30 minutes after vaccination.”

All COVID-19 vaccine recipients should be observed for 15 minutes, regardless of history. The Food and Drug Administration has approved two messenger RNA vaccines for COVID-19, both having an efficacy of about 95%: one developed by Pfizer Inc. (NYC) and BioNTech (Mainz, DEU), and the other by Moderna Inc. (Cambridge, MA).

“At this point, we think that it [anaphylactic shock] is something that is seen with both vaccines and, therefore, our recommendations apply to both vaccines,” Messonnier said. “As you can imagine, there are tremendous efforts underway right now to try to understand what the cause of these severe allergic reaction with both vaccines might be.”

In interim clinical guidance on anaphylaxis, the CDC goes into more detail, including these specific contraindications for both vaccines.3

The CDC considers a history of the following to be a contraindication to vaccination with both the Pfizer-BioNTech and Moderna COVID-19 vaccines:

  • Severe allergic reaction (e.g., anaphylaxis) after a previous dose of an mRNA COVID-19 vaccine or any of its components.
  • Immediate allergic reaction of any severity to a previous dose of an mRNA COVID-19 vaccine or any of its components (including polyethylene glycol [PEG]). These persons should not receive mRNA COVID-19 vaccination at this time unless they have been evaluated by an allergist-immunologist and it is determined that the person can safely receive the vaccine — under observation, in a setting with advanced medical care available.
  • Immediate allergic reaction of any severity to polysorbate (because of potential cross-reactive hypersensitivity with the vaccine ingredient PEG).

The CDC considers a history of any immediate allergic reaction to any other vaccine or injectable therapy — not related to a component of mRNA COVID-19 vaccines or polysorbate — as a precaution but not a contraindication to vaccination for COVID-19.

“We want to be sure that any administration site that is any place that is administering the vaccine is prepared to treat somebody if they had a severe allergic reaction,” Messonnier said. “Again, these events are rare. But immunization sites needs to be prepared. Their staff need to be trained, and they need to know what to do if a patient has anaphylaxis.”

REFERENCES

  1. Castells, MC. Phillips EJ. Maintaining safety with SARS-CoV-2 vaccines. New Engl J Med 2020; Dec 30:NEJMra2035343. doi: 10.1056/NEJMra2035343. [Online ahead of print].
  2. CDC COVID-19 Response Team; Food and Drug Administration. Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 vaccine — United States, December 14-23, 2020. MMWR Morb Mortal Wkly Rep 2021;70:46-51.
  3. Centers for Disease Control and Prevention. Interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States. Last reviewed Jan. 6, 2021. https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html