In this editorial letter, published by the New England Journal of Medicine, Blumenthal et al. report on 12 cases of large local reactions to the COVID-19 mRNA-1273 vaccine from Moderna. They found that these delayed skin reactions occurred at the point of injection up to 11 days after the first dose of vaccine. Ultimately, all 12 patients were encouraged to receive the second dose and completed their vaccination regimen safely. Half of the patients had no reaction to the second dose, while the others experienced a reaction milder than or comparable to their reaction to the first dose, though with an earlier onset time. After over 60,000 Mass General Brigham employees received the first dose of an mRNA COVID-19 vaccine, Blumenthal et al. analyze the symptom-surveys completed by more than 50,000 employees. This research letter in JAMA uncovered that vaccine-related anaphylaxis occurred in just 2.47 vaccinations out of every 10,000, and none of the cases of anaphylaxis required medication to maintain normal blood pressure or a breathing tube be placed. However, that result is nearly 100 times greater than the incidence rate reported by the US Centers for Disease Control and Prevention (CDC), at 0.025 vaccinations per 10,000. Despite this significant difference, even the larger rate of anaphylaxis is relatively low and comparable to other common healthcare exposures.
A simplified version of Table 1. Anaphylaxis was confirmed using two separate sets of criteria, the Brighton criteria (7 Pfizer-BioNTech cases, 7 Moderna cases) and the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network criteria (4 Pfizer-BioNTech cases, 5 Moderna cases). “Confirmed anaphylaxis” cases presented symptoms consistent with anaphylaxis according to either set of criteria, and some instances were consistent with both (4 Pfizer-BioNTech cases, 3 Moderna cases).
This analysis, led by Mass General allergist and researcher Dr. Lacey Robinson, assesses cutaneous reactions (like rash and hives) among over 40,000 symptom surveys completed by Mass General Brigham employees for 3 days following COVID-19 vaccination. The data show that 1.9% of respondents experienced a cutaneous reaction to the first dose of vaccination, and only approximately 1 in 6 of those also reacted to the second dose. Additionally, of the respondents who did not react to the first dose, 2.3% experienced a cutaneous reaction to the second dose. A cutaneous reaction to the first dose is not a contraindication to receiving the second dose, and a reaction to the second dose is unlikely even after reacting to the first dose. 
Dr. Anna Wolfson, Mass General allergist and researcher, led a study on skin testing for polyethylene glycol (PEG) allergy among 80 patients who experienced allergic symptoms to the first dose of an mRNA COVID-19 vaccination. 70 of those patients received the second dose, with 89% of them experiencing no or minor symptoms and 3% requiring epinephrine. 3 patients who tested positive to PEG skin testing then tolerated the second dose of vaccine safely. The analysis concluded that most patients reporting allergic symptoms to the first dose can safely receive the second dose, regardless of skin testing results. 
Analyzing a cohort of Mass General employees who experienced allergic symptoms after the first dose of 2-dose mRNA COVID-19 vaccination, Dr. Lacey Robinson assessed the risk of those patients not receiving their second dose. The analysis found that patients were 5-fold more likely not to complete their vaccination if they experience allergic symptoms after the first dose, which increases substantially to 23-fold if the reported allergic symptoms were severe (like anaphylaxis). Despite this, among patients who received a second dose after reporting any allergic symptoms to the first dose, only 17% experienced allergic symptoms to the second dose, none of which were severe.
A team of UK researchers, along with MGH allergy specialist Dr. Kimberly Blumenthal, addressed concerns about allergic reactions to the Pfizer-BioNTech and Moderna COVID-19 vaccines in The BMJ. These vaccines have been reported to cause allergic reactions, but severe reactions were very rare (between 2.5 and 11 cases per one million Americans). The authors conclude that the only individuals who cannot get this vaccine are those with a history of a severe allergic reaction to the vaccines’ ingredients (i.e. polyethylene glycol [PEG]); thus people with allergies to other foods or medications should feel assured that they are not at greater risk of allergic reaction to the vaccines.
Banerji et al. authored this special article for the Journal of Allergy and Clinical Immunology: In Practice to guide practicing allergists on the identification and treatment of allergic reactions to authorized COVID-19 vaccines. Building a framework from the current data and information about the vaccines from Pfizer and Moderna, the authors provide a background on the potential allergic ingredients in the vaccines (Polyethylene glycol [PEG] and polysorbate 80), the best clinical approach to vaccine reactions, and advice on directing patients concerned about reactions to vaccination.
