Administration of a Second Dose of the Moderna COVID-19 Vaccine After an Immediate Hypersensitivity Reaction With the First Dose: Two Case Reports
Authors: S. Shahzad Mustafa, Allison Ramsey, Mary L. Staicu
Journal: Annals of Internal Medicine (2021)

Letters6 April 2021Administration of a Second Dose of the Moderna COVID-19 Vaccine After an Immediate Hypersensitivity Reaction With the First Dose: Two Case ReportsFREES. Shahzad Mustafa, MD, Allison Ramsey, MD, and Mary L. Staicu, PharmDS. Shahzad Mustafa, MDRochester Regional Health and University of Rochester, Rochester, New YorkSearch for more papers by this author, Allison Ramsey, MDRochester Regional Health and University of Rochester, Rochester, New YorkSearch for more papers by this author, and Mary L. Staicu, PharmDRochester Regional Health, Rochester, New YorkSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L21-0104 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: In December 2020, the U.S. Food and Drug Administration issued an emergency use authorization for the Pfizer-BioNTech and Moderna messenger RNA vaccines for the prevention of COVID-19. This authorization was a significant step toward mitigating the burden of the disease. Nevertheless, hypersensitivity reactions to these vaccines are being reported (5.0 and 2.8 cases per million doses for the Pfizer-BioNTech and Moderna vaccines, respectively) (1), and these rates are higher than those for other similar vaccines (1.3 cases per million doses) (2). No deaths from these COVID-19 vaccines have been reported. However, guidelines from the Centers for Disease Control and Prevention recommend avoiding subsequent vaccine doses in persons who have any immediate hypersensitivity reaction with the first dose (3). Although others have reported skin testing protocols to assess the risk of these patients receiving a second dose (4), there are conflicting opinions about how this information should be used. For other vaccines, if the skin test results are positive and the patient requires subsequent doses, the vaccine is administered in graded doses under observation (5).Objective: To provide what we believe to be the first report using graded doses to successfully administer a second dose of the Moderna vaccine to 2 patients who had an immediate hypersensitivity reaction with the first dose.Case Reports: Patient 1 is a 64-year-old woman with a history of shellfish allergy who received dose 1 of the Moderna vaccine on 23 December 2020. Within 10 minutes, she had generalized pruritus, urticaria, and self-reported tachycardia but no angioedema, respiratory or gastrointestinal symptoms, or hypotension. Medical personnel at the vaccination site evaluated her and treated her with 50 mg of oral diphenhydramine. Her symptoms resolved within 90 minutes.Patient 2 is a 39-year-old woman with a history of allergic rhinitis who received dose 1 of the Moderna vaccine on 5 January 2021 and developed chest and neck urticaria within 15 minutes. Medical personnel treated her with 25 mg of oral diphenhydramine at the vaccination site, but she went on to develop mild facial angioedema within 30 minutes of vaccination. She was transported by ambulance to the emergency department, where she received 20 mg of intravenous famotidine and 125 mg of methylprednisolone without further progression of symptoms during 2 hours of observation. She was then discharged to home in stable condition.Both patients were referred to our allergy practice for further evaluation. 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 (4). 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. Both patients worked in health care settings with repeated exposure to patients with COVID-19 and participated in shared decision making about proceeding with the second dose of the vaccine. As a result, we administered the vaccine without premedication through a graded dosing protocol as previously described for other vaccines (Table) (5). Patient 1 had no symptoms during the protocol. Patient 2 reported pruritus after doses 2 and 5, but it resolved without medical intervention. Both patients reported no additional symptoms over the following 24 hours. 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.Table. Protocol for Graded Administration of Second Dose of Moderna COVID-19 VaccineDiscussion: Our experience highlights several important points. First, persons who have an immediate hypersensitivity reaction to dose 1 of the Pfizer-BioNTech or Moderna vaccine should not automatically defer dose 2. Instead, referral to an allergy and immunology physician for further evaluation and management should be considered. Second, although the mechanism of hypersensitivity reaction to messenger RNA vaccines is uncertain, skin testing may guide further vaccine administration. Third, we have shown that dose 2 of the Moderna vaccine can be safely administered through a graded dosing protocol to persons who have symptoms consistent with an immediate hypersensitivity reaction to dose 1, resulting in protective antibodies against COVID-19. Limitations of our report include the uncertainty surrounding patients who experience anaphylaxis with the first dose of the Moderna vaccine and whether or not a single dose would be sufficiently protective in these persons. Further study in these rare cases is warranted.References1. Shimabukuro T. COVID-19 vaccine safety update. Advisory Committee on Immunization Practices (ACIP). 27 January 2021. Accessed at www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-01/06-COVID-Shimabukuro.pdf on 20 March 2021. Google Scholar2. McNeil MM, Weintraub ES, Duffy J, et al. Risk of anaphylaxis after vaccination in children and adults. J Allergy Clin Immunol. 2016;137:868-78. [PMID: 26452420] doi:10.1016/j.jaci.2015.07.048 CrossrefMedlineGoogle Scholar3. Centers for Disease Control and Prevention. What to do if you have an allergic reaction after getting a COVID-19 vaccine. Accessed at www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/allergic-reaction.html on 5 February 2021. Google Scholar4. Banerji A, Wickner PG, Saff R, et al. mRNA vaccines to prevent COVID-19 disease and reported allergic reactions: current evidence and suggested approach. J Allergy Clin Immunol Pract. 2020. [PMID: 33388478] doi:10.1016/j.jaip.2020.12.047 CrossrefGoogle Scholar5. Kelso JM, Greenhawt MJ, Li JT, et al. Adverse reactions to vaccines practice parameter 2012 update. J Allergy Clin Immunol. 2012;130:25-43. [PMID: 22608573] doi:10.1016/j.jaci.2012.04.003 CrossrefMedlineGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Daniel Highkin, MDThe Vancouver Clinic, Vancouver WA5 April 2021 Hypersensitivity to first dose of an mRNA vaccine Current CDC guidance is for the patient to receive a single dose of the Janssen vaccine instead of the second dose of the mRNA vaccine. This is the one exception to the prohibition against an individual receiving doses of two different vaccines. This is a much simpler approach, and now that the Janssen vaccine is becoming more widely available, it would avoid putting the patient at risk of a more severe hypersensitivity reaction or anaphylaxis. S Shahzad MustafaRochester Regional Health6 April 2021 Re: hypersensitivity to first dose of mRNA Vaccine Thank you for this thoughtful comment. These CDC guidelines are recent, and although using a different vaccine is a practical approach to patients with potential hypersensitivity to dose 1 of an mRNA vaccine, there remains lack of evidence regarding safety or efficacy of this approach. Vaccine availability, although greatly improved, is still heterogeneous throughout the US, and especially globally. Therefore, our reported approach provides yet another management option to facilitate vaccination safely and effectively in patients reporting reactions to dose 1 of an mRNA vaccine. Author, Article, and Disclosure InformationAuthors: S. Shahzad Mustafa, MD; Allison Ramsey, MD; Mary L. Staicu, PharmDAffiliations: Rochester Regional Health and University of Rochester, Rochester, New YorkRochester Regional Health, Rochester, New YorkDisclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L21-0104.Corresponding Author: S. Shahzad Mustafa, MD, Rochester Regional Health, 222 Alexander Street, Suite 3000, Rochester, NY 14607; e-mail, shahzad.mustafa@rochesterregional.org.This article was published at Annals.org on 6 April 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCOVID-19 vaccine provocation test outcome in high-risk allergic patients: A retrospective study from a tertiary hospital in IndonesiaDiagnostic accuracy of vaccine and vaccine excipient testing in the setting of allergic reactions to COVID ‐19 vaccines: A systematic review and meta‐analysisAllergological study in patients vaccinated against COVID-19 with suspected allergic reactionsAssessment of Immediate Allergic Reactions After Immunization With the Pfizer BNT162b2 Vaccine Using Intradermal Skin Testing With the COVID-19 VaccinesAdverse Reactions to Anti-Infective Vaccines: an Emerging Problem in the COVID-19 EraThe adverse reactions to vaccines practice parameter 10 years on—what have we learned?Graded coronavirus disease 2019 vaccine administrationImmediate Hypersensitivity Reactions Induced by COVID-19 Vaccines: Current Trends, Potential Mechanisms and Prevention StrategiesSuccessful graded-dose challenge of the Janssen vaccine against SARS-CoV-2 in a high-risk patientRisk of Second Allergic Reaction to SARS-CoV-2 VaccinesThe Side Effects and Adverse Clinical Cases Reported after COVID-19 ImmunizationAllergic reactions to coronavirus disease 2019 vaccines and addressing vaccine hesitancyCohort experience of second messenger RNA vaccine dose tolerance after an initial-dose reactionUtility and futility of skin testing to address concerns surrounding messenger RNA coronavirus disease 2019 vaccine reactionsDrug AllergyCOVID-19 mRNA VaccinesCoronavirus disease 2019 vaccine hypersensitivity evaluated with vaccine and excipient allergy skin testingA rapid review of the prevalence and onset of urticaria triggered by COVID-19 vaccineImmediate Reactions After the First Dose of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Messenger RNA Vaccines Do Not Preclude Second-Dose AdministrationGraded Administration of Second Dose of Moderna and Pfizer-BioNTech COVID-19 mRNA Vaccines in Patients With Hypersensitivity to First DoseCOVID-19 mRNA vaccine allergyAnaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines: a systematic review and meta-analysisCOVID-19 vaccine-related presumed allergic reactions and second dose administration by using a two-step graded protocolCounting on COVID-19 Vaccine: Insights into the Current Strategies, Progress and Future Challengesmrna-1273The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus ApproachFirst-Dose mRNA COVID-19 Vaccine Allergic Reactions: Limited Role for Excipient Skin TestingImmediate-Type Systemic Hypersensitivity Reactions After the Inactivated SARS-CoV-2 Vaccine in Healthcare WorkersCoronaVac COVID-19 Vaccine-Induced Anaphylaxis: Clinical Characteristics and Revaccination Outcomes August 2021Volume 174, Issue 8 Page: 1177-1178 Keywords Allergy and immunology Antibodies COVID-19 Disclosure Hypersensitivity Medical staff Messenger RNA Pruritus Urticaria Vaccines ePublished: 6 April 2021 Issue Published: August 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...