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Gradual Dosing Of COVID-19 Vaccines May Be Safe After Allergic Reactions

COVID-19 vaccine.

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Key Takeaways

  • Allergic reactions to the mRNA COVID-19 vaccines are rare but happen.
  • The CDC recommends using another type of COVID-19 vaccine after an allergic reaction to an initial dose of an mRNA vaccine.
  • Experts have found that administering the second dose in smaller, subsequent shots to a patient who experienced a previous allergic reaction may be safe and effective.

If you've experienced an allergic reaction to the Pfizer-BioNTech or Moderna COVID-19 vaccines, the Centers for Disease Control and Prevention (CDC) urges you to ask your doctor about getting a different type of shot. But a new pair of case reports finds that, in some situations, it may be possible to complete the two-dose vaccine series if you've experienced an allergic reaction.

The brief reports, which were published in the Annals of Internal Medicine, detail how two patients were able to receive their second doses under careful medical supervision after having allergic reactions to their first doses of the Moderna vaccine.

Allergic reactions to the mRNA COVID-19 vaccines aren’t common, but they do happen. Research has shown that there are five cases per million doses for the Pfizer-BioNTech vaccine and 2.8 cases per million doses for the Moderna vaccine.

The researchers note that, with other vaccines, if patients have positive skin allergy test results and more doses are needed, the vaccine is administered in graded—meaning small, subsequent—doses under medical observation.

The CDC advises exploring other types of vaccines if a person has an allergic reaction to the mRNA vaccine. However, with the administration of the Johnson & Johnson vaccine paused and under review, that may not currently be an option.

“We felt it was important to report that dose two of an mRNA vaccine can be safely and effectively administered to individuals who experience symptoms consistent with an allergic reaction to dose one,” lead study author Syed Shahzad Mustafa, MD, lead physician of allergy, immunology, and rheumatology at Rochester Regional Health and clinical associate professor of medicine at the University of Rochester School of Medicine and Dentistry in New York, tells Verywell.

How Gradual Dosing Worked in Two Patients

The first patient examined in the report was a 64-year-old woman with a history of a shellfish allergy. She received her first dose of the Moderna vaccine on December 23, 2020, and, within minutes, had itchy skin, hives, and rapid heartbeat. She was evaluated by medical personnel and given 50 milligrams (mg) of the antihistamine diphenhydramine. Her symptoms improved within 90 minutes.

The second patient was a 39-year-old woman with a history of hay fever who received her first dose of the Moderna vaccine on January 5, 2021. She developed hives on her chest and neck within 15 minutes. Medical personnel treated her with 25 mg of diphenhydramine at the vaccination site, but she developed mild facial swelling within 30 minutes of being vaccinated. She was taken by ambulance to the emergency room, where she received IV medications. Her symptoms didn’t progress during another two hours of observation and she was discharged in stable condition.

Both patients were referred to Rochester Regional Health for further evaluation. There, Mustafa and his team conducted testing for polyethylene glycol and polysorbate—two ingredients found in the Moderna vaccine—along with the actual Moderna vaccine, using remaining overfill from previously used vaccine vials. Results from skin prick tests were negative for all components in both patients, but both patients had positive results on intradermal (under the skin) testing with the Moderna vaccine.

The patients worked in healthcare settings and were repeatedly exposed to patients with COVID-19. They each decided to get the second dose of the vaccine.

Mustafa and his team gave the vaccine to each patient in a graded dosing protocol previously used for other vaccines in people with allergic reactions. They both received five smaller doses of the vaccine, spread 15 minutes apart.

The first patient had no symptoms, and the second patient developed itchy skin after doses two and five—but it went away without medical intervention. Both patients had no additional symptoms over the next 24 hours and, three to four weeks after receiving their second dose, developed antibodies, suggesting the graded dosing was effective and safe.

What This Means For You

If you had an allergic reaction or suspected allergic reaction to the first dose of an mRNA COVID-19 vaccine, talk to your doctor about the possibility of a graded plan for your second dose. They may recommend this technique for receiving your second dose or taking a different type of vaccine instead.

Why Graded Dosing Works for Some Patients

Mustafa says it's “still uncertain” why graded dosing works for some patients, adding, “we have a lot to learn.” But, he says, “graded dosing can theoretically desensitize the patient to the allergy.”

“We provided dose two in graded dosing because we felt it was the safest approach to facilitate complete vaccination in these two individuals who work in the medical setting,” he says.

Graded dosing is often used “so that you can monitor for reactions,” Jamie Alan, PhD, associate professor of pharmacology at Michigan State University, tells Verywell. “It's a way to get some vaccine in before a full allergic response occurs. It's a bit like rapid desensitization.”

Alan points out that this is “not a new idea,” adding that, “there are many papers and protocols on other vaccines that can be given in a graded dose.”

Mustafa is hopeful that other physicians will consider doing the same in people who have allergic reactions to the first dose of an mRNA vaccine. “Even if patients report allergic-type reactions to dose one of an mRNA vaccine, dose two does not need to be automatically deferred,” he says. He wants other physicians and patients to know that there are other options beyond vaccinating these patients with the Johnson & Johnson vaccine—which isn’t currently an option. That strategy also “has not been studied for safety or efficacy,” Mustafa points out.

“We believe patients can still receive dose two of the mRNA vaccine through graded dosing if there is a high suspicion of a true allergic reaction to dose one,” he says. 

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.

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  1. Centers for Disease Control and Prevention. Information about COVID-19 vaccines for people with allergies. Updated March 25, 2021.

  2. Mustafa SS, Ramsey A, Staicu ML. Administration of a second dose of the Moderna COVID-19 vaccine after an immediate hypersensitivity reaction with the first dose: two case reportsAnn Intern Med. Published online April 6, 2021. doi:10.7326/L21-0104

  3. Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases. COVID-19 vaccine safety update. Published January 27, 2021.

  4. United States Food and Drug Administration. Joint CDC and FDA statement on Johnson & Johnson COVID-19 vaccine. Published April 13, 2021.