Delayed Localized Hypersensitivity Reactions to the Moderna COVID-19 Vaccine | Dermatology | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

Delayed Localized Hypersensitivity Reactions to the Moderna COVID-19 VaccineA Case Series

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What are the clinical course and histopathologic examination findings for delayed injection-site reactions to the Moderna coronavirus disease 2019 (COVID-19) vaccine?

Findings  The Moderna COVID-19 vaccine may cause a delayed localized hypersensitivity reaction with a median latency to onset of 7 days after vaccine administration. This pruritic and variably tender reaction has a median duration of 5 days, but may persist for up to 21 days, and may occur again and sooner after the second vaccine dose; no serious adverse events were observed in association with this cutaneous reaction to the Moderna COVID-19 vaccine.

Meaning  Self-limited localized delayed hypersensitivity reactions to the Moderna COVID-19 vaccine may occur, and in contrast with immediate hypersensitivity reactions, these delayed hypersensitivity reactions are not a contraindication to subsequent vaccination.

Abstract

Importance  In response to the coronavirus disease 2019 (COVID-19) pandemic, 2 mRNA vaccines (Pfizer-BioNTech and Moderna) received emergency use authorization from the US Food and Drug Administration in December 2020. Some patients in the US have developed delayed localized cutaneous vaccine reactions that have been dubbed “COVID arm.”

Objective  To describe the course of localized cutaneous injection-site reactions to the Moderna COVID-19 vaccine, subsequent reactions to the second vaccine dose, and to characterize the findings of histopathologic examination of the reaction.

Design, Setting, and Participants  This retrospective case series study was performed at Yale New Haven Hospital, a tertiary medical center in New Haven, Connecticut, with 16 patients referred with localized cutaneous injection-site reactions from January 20 through February 12, 2021.

Main Outcomes and Measures  We collected each patient’s demographic information, a brief relevant medical history, clinical course, and treatment (if any); and considered the findings of a histopathologic examination of 1 skin biopsy specimen.

Results  Of 16 patients (median [range] age, 38 [25-89] years; 13 [81%] women), 14 patients self-identified as White and 2 as Asian. The delayed localized cutaneous reactions developed in a median (range) of 7 (2-12) days after receiving the Moderna COVID-19 vaccine. These reactions occurred at or near the injection site and were described as pruritic, painful, and edematous pink plaques. None of the participants had received the Pfizer-BioNTech vaccine. Results of a skin biopsy specimen demonstrated a mild predominantly perivascular mixed infiltrate with lymphocytes and eosinophils, consistent with a dermal hypersensitivity reaction. Of participants who had a reaction to first vaccine dose (15 of 16 patients), most (11 patients) developed a similar localized injection-site reaction to the second vaccine dose; most (10 patients) also developed the second reaction sooner as compared with the first-dose reaction.

Conclusions and Relevance  Clinical and histopathologic findings of this case series study indicate that the localized injection-site reactions to the Moderna COVID-19 vaccine are a delayed hypersensitivity reaction. These reactions may occur sooner after the second dose, but they are self-limited and not associated with serious vaccine adverse effects. In contrast to immediate hypersensitivity reactions (eg, anaphylaxis, urticaria), these delayed reactions (dubbed “COVID arm”) are not a contraindication to subsequent vaccination.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Accepted for Publication: March 18, 2021.

Published Online: May 12, 2021. doi:10.1001/jamadermatol.2021.1214

Corresponding Author: Alicia J. Little, MD, PhD, Department of Dermatology, Yale School of Medicine, 333 Cedar St, PO Box 208059, New Haven, CT 06520 (alicia.little@yale.edu).

Author Contributions: Drs Little and Johnston had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Johnston, Galan, Little.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Johnston, Little.

Administrative, technical, or material support: Johnston, Galan, Watsky.

Supervision: Little.

Conflict of Interest Disclosures: Dr Little reported a grant from the National Center for Advancing Translational Science (CTSA No. KL2 TR001862), which is a component of the National Institutes of Health, and a Women’s Health Career Development Award from the Dermatology Foundation during the conduct of the study. Dr Watsky reported equity in Johnson & Johnson held by his spouse’s retirement fund outside the submitted work. No other disclosures were reported.

Disclaimer: The publication's contents are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health.

Additional Contributions: We thank the 4 patients whose images were published for granting permission. We thank Christine Ko, MD, Department of Dermatology, Yale University School of Medicine, for mentorship and assistance with editing the manuscript. For assistance with referred patients, we thank Jacob Siegel, MD, Kathleen Suozzi, MD, Mark Goldstein, MD, Mark Grossman, MD, and Barry Richter, MD, Department of Dermatology, Yale University School of Medicine, and Mark Abdelmalek, MD, Dermatology of Philadelphia–Mohs Surgery Center and Department of Dermatology, University of Pennsylvania Perelman School of Medicine. We thank Gauri Panse, MD, Departments of Dermatology and Pathology, Yale University School of Medicine, for assistance with reviewing the histopathology findings. We thank Mary Tomayko, MD, PhD, Department of Dermatology, Yale University School of Medicine, for insights into potential immunopathogenesis of “COVID arm.” We thank David Banach, MD, Department of Medicine (Infectious Disease), University of Connecticut School of Medicine, and Richard Martinello, MD, Departments of Medicine (Infectious Disease) and Pediatrics, Yale University School of Medicine and Department of Infection Prevention, Yale New Haven Health, for insights into SARS-CoV-2 vaccine administration and reported adverse effects. None of these individuals were compensated.

References
1.
Jin  Y , Yang  H , Ji  W ,  et al.  Virology, epidemiology, pathogenesis, and control of COVID-19.   Viruses. 2020;12(4):372. doi:10.3390/v12040372PubMedGoogle ScholarCrossref
2.
Centers for Disease Control and Prevention. COVID Data Tracker. Accessed February 12, 2021. http://covid.cdc.gov/covid-data-tracker/#global-counts-rates
3.
Centers for Disease Control and Prevention. Local reactions, systemic reactions, adverse events, and serious adverse events: Moderna COVID-19 vaccine. Accessed February 12, 2021. https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/reactogenicity.html
4.
Baden  LR , El Sahly  HM , Essink  B ,  et al; COVE Study Group.  Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.   N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389 PubMedGoogle ScholarCrossref
5.
Blumenthal  KG , Freeman  EE , Saff  RR ,  et al.  Delayed large local reactions to mRNA-1273 vaccine against SARS-CoV-2.   N Engl J Med. 2021;384(13):1273-1277. doi:10.1056/NEJMc2102131 PubMedGoogle Scholar
6.
Fung  MA .  The clinical and histopathologic spectrum of “dermal hypersensitivity reactions,” a nonspecific histologic diagnosis that is not very useful in clinical practice, and the concept of a “dermal hypersensitivity reaction pattern.”   J Am Acad Dermatol. 2002;47(6):898-907. doi:10.1067/mjd.2002.120908 PubMedGoogle ScholarCrossref
7.
Copaescu  A , Gibson  A , Li  Y , Trubiano  JA , Phillips  EJ .  An updated review of the diagnostic methods in delayed drug hypersensitivity.   Front Pharmacol. 2021;11:573573. doi:10.3389/fphar.2020.573573PubMedGoogle Scholar
8.
Cabanillas  B , Akdis  C , Novak  N .  Allergic reactions to the first COVID-19 vaccine: a potential role of Polyethylene glycol?   Allergy. 2020. doi:10.1111/all.14711PubMedGoogle Scholar
9.
Centers for Disease Control and Prevention. COVID-19 vaccine distribution allocations by jurisdiction–Moderna. Accessed February 12, 2021. https://data.cdc.gov/Vaccinations/COVID-19-Vaccine-Distribution-Allocations-by-Juris/b7pe-5nws
10.
Centers for Disease Control and Prevention. COVID-19 vaccine distribution allocations by jurisdiction–Pfizer. Accessed February 12, 2021. https://data.cdc.gov/Vaccinations/COVID-19-Vaccine-Distribution-Allocations-by-Juris/saz5-9hgg
11.
Centers for Disease Control and Prevention. Demographic characteristics of people receiving COVID-19 vaccines in the United States. Accessed February 12, 2021. https://covid.cdc.gov/covid-data-tracker/#vaccination-demographic
12.
McNeil  MM , DeStefano  F .  Vaccine-associated hypersensitivity.   J Allergy Clin Immunol. 2018;141(2):463-472. doi:10.1016/j.jaci.2017.12.971 PubMedGoogle ScholarCrossref
13.
Cook  IF .  Sex differences in injection site reactions with human vaccines.   Hum Vaccin. 2009;5(7):441-449. doi:10.4161/hv.8476 PubMedGoogle ScholarCrossref
14.
Centers for Disease Control and Prevention. Interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States. Accessed February 13, 2021. http://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html#contraindications
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close