Despite Allergic-Type Reactions, Military Study Found Many Patients Can Tolerate Second Dose of COVID-19 mRNA Vaccine

In January 2021, paratroopers assigned to the 82nd Airborne Division wait in line to receive the COVID-19 vaccine at Fort Bragg, NC. Fort Bragg recipients participated in a study showing that most people could safely get a second mRNA dose even if they had some allergic reaction to the first. U.S. Army photo by Master Sgt. Alexander Burnett

BETHESDA, MD — Although serious allergic reactions to mRNA vaccines are extremely rare, fear of them has driven hesitancy among some potential recipients. That especially has been the case when an adverse effect occurred after the first dose.

A recent military study has determined, however, that most patients with reported symptoms of allergic reactions to the mRNA COVID-19 vaccines can safely tolerate the second dose.

The report in the journal Annals of Allergy, Asthma & Immunology discusses the multicenter retrospective review of patients referred to military allergy clinics from January 2021 to November 2021 for adverse events following immunization (AEFI) after receipt of either of the two messenger RNA (mRNA) COVID-19 vaccines that were authorized for use. Involved in the study were the Bethesda, MD, Walter Reed National Military Medical Center in Bethesda, MD; Portsmouth, VA, Naval Medical Center Portsmouth, VA; and Womack Army Medical Center at Fort Bragg, NC.¹

The data were pooled during the initial rollout of the mRNA vaccines. Individuals with at least one symptom consistent with a hypersensitivity reaction within 24 hours of the first dose were included in the study.

“This study demonstrated that most people who thought they were allergic to the mRNA COVID-19 vaccine were able to tolerate the second dose with no ill effects,” Rachel U. Lee, MD, MBA, FAAAAI, study author and a physician at the Bethesda, MD, Walter Reed National Military Medical Center’s Department of Allergy, Asthma & Immunology, told U.S. Medicine. “People who may have had (or think they may have had) an allergy to the vaccine can get subsequent doses to finish the series or future boosters. The results are significant because vaccines are a crucial part of fighting this pandemic and developing immunity to this virus.”

Adverse events after receipt of mRNA COVID-19 vaccines, including anaphylaxis, are estimated to occur at a rate of 2.5 to 11 cases per 1 million doses. Studies have found these individuals have tolerance to vaccine challenge, which suggests the reactions are likely not the immune system overreacting to an allergen by producing immunoglobulin (Ig)E antibodies. The national Centers for Disease Control and Prevention (CDC) considers immediate, nonsevere, allergic-type reactions after a dose of the COVID-19 vaccine a precaution to a subsequent dose of the same vaccine, rather than a reason not to receive one.

In the MHS study, 391 patients initially were referred for concern of an AEFI after either mRNA COVID-19 vaccine, and 65s met the study’s inclusion criteria. Most of the patients included in the study were of female sex (78%t), and the mean age was 42 (13-78) years. Fifty-eight (88%) of the patients received the Pfizer-BioNTech COVID-19 vaccine.

Lee suggested that most of the study participants were female, likely because “women are more likely to seek medical attention for symptoms, while men will often ignore them (or not seek care).” Also, women are different biologically and behaviorally, so Lee said he expects they will have different reactions to vaccines.

The primary symptoms reported were:

• The sensation of throat closure (45%),
• Pruritus (31%),
• Lightheadedness (30%),
• Flushing (27%),
• Urticaria (24%),
• Shortness of breath (19%),
• Nausea (16%),
• Angioedema (9%),
• Tachycardia (4%),
• Hoarse voice (4%) or
• A combination.

In those cases, an allergist made recommendations regarding testing, vaccine challenge or vaccine avoidance for patients. In most situations, the vaccine and component testing were done with a full-strength prick test followed by 1:100 dilution intradermal. Vaccine challenge was offered to most patients at full dose, except for three patients who received split dosing at the allergist’s discretion. Premedication was not routinely used. Skin testing was performed to the Pfizer-BioNTech COVID-19 vaccine, polyethylene glycol and polysorbate. The likelihood of anaphylaxis was based on the Brighton Collaboration Criteria.

With 26 patients undergoing skin-prick testing, one skin-test result was positive to the Pfizer COVID-19 vaccine on intradermal testing at 1:100, but all other skin-test results were negative. Twenty-seven (42%) patients met the Brighton levels 1 to 3 classifications.

For second dose recommendations, the allergist advised seven patients (11%) against getting the dose, five (8%) declined, and 53 (82%) underwent vaccine challenge. Of those who underwent vaccine challenge, 47 (89%) had no further symptoms, while 6 (11%) experienced a recurrence of symptoms.

The study found that most patients with reported symptoms of allergic reactions to the mRNA COVID-19 vaccines can tolerate the second dose. Nearly 90% of patients with first-dose allergic symptoms tolerated the second dose with no recurrence of symptoms, and all but one had symptoms that were mild and self-limited, according to the authors, who added that most of the reactions were self-reported symptoms without objective findings of anaphylaxis.

Because adverse reactions can lead to vaccine hesitancy and incomplete vaccination in patients, these studies are critical to supporting the vaccination effort, researchers suggested. Further studies are needed to understand mechanisms of AEFI after mRNA COVID-19 vaccinations, they pointed out.

“The major implications (of the results) would point back to the significance of our study: a patient’s reaction (perceived or otherwise) to an initial dose of the vaccine won’t necessarily preclude that patient from continuing to receive doses within that vaccine series,” Lee wrote in an email. “Since we know how effective the vaccine is in limiting the spread of the virus, this is important in helping us further our public health efforts. Many people believe they are allergic to vaccines and refuse to get vaccines. However, studies like this and others show that with proper clinical evaluation, most people with vaccine allergy concerns can get vaccinated safely.”

The Defense Health Agency has a 24/7 resource for military members and beneficiaries to discuss vaccine concerns, the Immunization Healthcare Support Center, which can be reached at 1-877-GET VACC. The CDC offers a similar resource for all citizens (not just military beneficiaries) at 1-800-CDC-INFO.