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Graded Administration of Second COVID-19 Vaccine Dose After Hypersensitivity

Patients who have an immediate hypersensitivity reaction to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine may be able to safely receive their second dose through a graded dosing protocol, according to a case series recently published in the Annals of Internal Medicine.

Current recommendations surrounding the administration of the second COVID-19 vaccine dose to those who experience an immediate hypersensitivity reaction to the first dose are conflicting. The Centers for Disease Control and Prevention states that administration of subsequent vaccine doses should be avoided in these patients while other reports state that skin testing protocols can be utilized to assess a patient’s risk.

In this report, the cases of 2 individuals who successfully received graded doses of the second dose of the Moderna COVID-19 vaccine after experiencing an immediate hypersensitivity reaction to the first dose are discussed.

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The first case involves a 64-year-old woman who experienced pruritis, urticaria, and self-reported tachycardia 10 minutes after receiving dose 1 of the Moderna vaccine. Her past medical history was significant for a shellfish allergy. The patient’s symptoms resolved approximately 90 minutes after receiving 50mg of diphenhydramine.

The second individual was a 39-year-old woman who developed chest and neck urticaria 15 minutes after receiving the first dose of the Moderna vaccine. She received 25mg diphenhydramine but subsequently developed facial angioedema. After receiving famotidine and methylprednisolone in the emergency department, her symptoms resolved.

Both patients were referred to an allergy clinic for further assessment. “We did skin prick and intradermal testing for polyethylene glycol, polysorbate, and the Moderna vaccine (using remaining overfill from previously used vaccine vials), following recommendations from Banerji and colleagues,” the authors explained. “Results from the skin prick were negative for all components in both patients, whereas both patients had positive results on intradermal testing with the Moderna vaccine.”

At the clinic, both patients agreed to participate in receiving the second vaccine dose using a graded dosing protocol and without premedication. Patient 1 reported experiencing no symptoms during the protocol. Patient 2 experienced pruritis after the second and fifth dose, however, she did not require medical intervention. “In addition, 3 to 4 weeks after receiving the second dose, both patients had IgG antibodies directed against the spike protein of COVID-19, suggesting vaccination was efficacious despite the graded dosing protocol,” the authors stated.

This case series demonstrates that receipt of a second dose of the COVID-19 vaccine may not necessarily need to be deferred in those who experience an immediate hypersensitivity to the first. For these patients, a referral to an allergy practice for evaluation and management, which may include a graded dosing protocol, could be considered.


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 reports. Annals of Internal Medicine. [Published online April 6, 2021]. doi: 10.7326/L21-0104.

This article originally appeared on MPR