A randomized double-blinded trial to assess recurrence of systemic allergic reactions following COVID-19 mRNA vaccination - 05/06/24

Doi : 10.1016/j.jaci.2024.03.001

Muhammad B. Khalid, MD ^a, Ellen Zektser, BSN, MPH ^a, Eric Chu, MA ^b, Min Li, PhD ^a, Joanna Utoh, MSN, FNP-C ^a, Patrick Ryan, BA ^c, Hanna S. Loving, PhD ^d, Roa Harb, MD ^d, Robbie Kattappuram, PharmD ^e, Lindsay Chatman, MSc ^a, Stella Hartono, MD, PhD ^a, Estefania Claudio-Etienne, PhD ^a, Guangping Sun, PhD ^a, Edward P. Feener, PhD ^f, Zhongbo Li ^g, Samuel K. Lai, PhD ^g, Quang Le, PhD ^h, Lawrence B. Schwartz, PhD ^h, Jonathan J. Lyons, MD ⁱ, Hirsh Komarow, MD ^j, Zhao-Hua Zhou, PhD ^k, Haniya Raza, DO, MPH ^c, Maryland Pao, MD ^c, Karen Laky, PhD ^a, Steven M. Holland, MD ^l, Erica Brittain, PhD ^m, Pamela A. Frischmeyer-Guerrerio, MD, PhD ^a,^⁎
^a Food Allergy Research Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
^b Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Md
^c Office of the Clinical Director, National Institute of Mental Health, National Institutes of Health, Bethesda, Md
^d Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Md
^e Investigational Drug Management and Research Section, Clinical Center, National Institutes of Health, Bethesda, Md
^f KalVista Pharmaceuticals, Cambridge, Mass
^g Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina Chapel Hill, Chapel Hill, NC
^h Department of Internal Medicine, Division of Rheumatology, Allergy, and Immunology, Virginia Commonwealth University, Richmond, Va
ⁱ Translational Allergic Immunopathology Unit, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
^j Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
^k Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Md
^l Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
^m Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md

^∗Corresponding author: Pamela A. Frischmeyer-Guerrerio, MD, PhD, Food Allergy Research Section, Laboratory of Allergic Diseases, NAID, NIH, MSC 1881, 10 Center Drive, Bethesda, MD 20892.Food Allergy Research SectionLaboratory of Allergic DiseasesNAIDNIHMSC 188110 Center DriveBethesdaMD20892

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Abstract

Background

Systemic allergic reactions (sARs) following coronavirus disease 2019 (COVID-19) mRNA vaccines were initially reported at a higher rate than after traditional vaccines.

Objective

We aimed to evaluate the safety of revaccination in these individuals and to interrogate mechanisms underlying these reactions.

Methods

In this randomized, double-blinded, phase 2 trial, participants aged 16 to 69 years who previously reported a convincing sAR to their first dose of COVID-19 mRNA vaccine were randomly assigned to receive a second dose of BNT162b2 (Comirnaty) vaccine and placebo on consecutive days in a blinded, 1:1 crossover fashion at the National Institutes of Health. An open-label BNT162b2 booster was offered 5 months later if the second dose did not result in severe sAR. None of the participants received the mRNA-1273 (Spikevax) vaccine during the study. The primary end point was recurrence of sAR following second dose and booster vaccination; exploratory end points included biomarker measurements.

Results

Of 111 screened participants, 18 were randomly assigned to receive study interventions. Eight received BNT162b2 second dose followed by placebo; 8 received placebo followed by BNT162b2 second dose; 2 withdrew before receiving any study intervention. All 16 participants received the booster dose. Following second dose and booster vaccination, sARs recurred in 2 participants (12.5%; 95% CI, 1.6 to 38.3). No sAR occurred after placebo. An anaphylaxis mimic, immunization stress-related response (ISRR), occurred more commonly than sARs following both vaccine and placebo and was associated with higher predose anxiety scores, paresthesias, and distinct vital sign and biomarker changes.

Conclusions

Our findings support revaccination of individuals who report sARs to COVID-19 mRNA vaccines. Distinct clinical and laboratory features may distinguish sARs from ISRRs.

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Key words : Anaphylaxis, COVID-19, mRNA, vaccine, immunization stress-related response, ISRR, allergic reaction, PEG

Abbreviations used : AE, CoFAR, COVID-19, FDA, HR, IQR, ISRR, NIAID, NIH, PEG, sAR, SBP

Plan

Methods

Study design and participants

Randomization and blinding

Clinical trial registration: ClinicalTrials.gov (NCT04977479), ClinicalTrials.gov Identifier: NCT04977479.

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Vol 153 - N° 6

P. 1634-1646 - juin 2024 Retour au numéro

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A randomized double-blinded trial to assess recurrence of systemic allergic reactions following COVID-19 mRNA vaccination - 05/06/24

Abstract

Background

Objective

Methods

Results

Conclusions

Plan

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