To the Editor:

Baden et al.1 report ~ above a step 3 clinical trial of the mRNA-1273 vaccine against SARS-CoV-2, and also they provide information on prompt injection-site reactions, which were observed in 84.2% the the participants ~ the first dose. The trial additionally showed that delayed injection-site reactions (defined in that trial as those with an start on or after work 8) arisen in 244 of the 30,420 entrants (0.8%) after the an initial dose and in 68 participants (0.2%) after the second dose. These reactions consisted of erythema, induration, and tenderness. The reactions frequently resolved over the following 4 come 5 days. However, these reactions to be not additional characterized, and links between reactions ~ the an initial dose and those ~ the second dose to be not listed to educate clinical care.

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figure 1.
Figure 1. Delayed Cutaneous reactions to mRNA-1273 Vaccine.

Shown are morphologic characteristics of delay cutaneous reactions to mRNA-1273 vaccine, consisting of annular plaques (in patient 1), uniformly edematous plaques (in patients 2, 6, and also 11), and targetoid plaques (in patience 3) close to the website of vaccination. In number of patients, there was significant induration the the plaques (e.g., in patient 8 and also 9). In enhancement to a localized rashes on the arm, two patients had actually other cutaneous symptoms, consisting of papules top top the palm and also fingers (Patient 5) and urticarial plaques on the elbows (Patient 6). Patients 1, 5, 8, 9, 11, and also 12 did not have a recurrence of large local reactions through the 2nd dose, although some patients had actually minimal erythema. In patients 2, 6, and 7, the reactions had an previously onset and were reduced grade after ~ the 2nd dose 보다 after the very first dose. In patient 3, 4, and also 10, the onset of the reactions after the 2nd dose was earlier than after ~ the an initial dose, yet the reaction to the 2 doses were of a similar grade. Part photographs were taken by the patients utilizing a mirror, therefore the pictures of the left and right arms might be transposed.

Table 1.
Table 1. Patients with Remarkable, Delayed, big Local reaction to the mRNA-1273 Vaccine.

We have additionally observed delayed big local reaction to the mRNA-1273 vaccine, through a typical onset on job 8 (range, 4 to 11) after the first dose. These reactions had a change appearance (Figure 1). Here, we report ~ above a series of 12 patients v these reactions, all of which appeared near the injection website after complete resolution of the early stage local and also systemic symptoms connected with vaccination. 5 of the reactions to be grade 3 plaques (≥10 centimeter in diameter) (Table 1). Part patients had concurrent systemic adverse effects, and amongst these patients, 2 had extr skin findings. Most patients received treatment for their symptoms (e.g., v ice and also antihistamines). Part patients obtained glucocorticoids (topical, oral, or both), and also 1 patient received antibiotic therapy for presumptive cellulitis. The symptoms fixed a mean of 6 job after onset (range, 2 to 11).

Our skepticism of delayed-type or T-cell–mediated hypersensitivity was supported by skin-biopsy specimens derived from a patient with a delayed huge local reaction that was not among the 12 patients explained here. Those specimens proved superficial perivascular and perifollicular lymphocytic infiltrates through rare eosinophils and also scattered mast cells (see Fig. S1 in the Supplementary Appendix, easily accessible with the complete text of this letter in ~

Given the neither neighborhood injection-site reactions nor delayed-type hypersensitivity reactions space contraindications to succeeding vaccination,2 all 12 patient were encouraged to obtain the 2nd dose and also completed your mRNA-1273 vaccination course. Although half the patient did not have a recurrence of large local reactions, three patients had actually recurrent reactions the were comparable to those ~ the initial dose, and three patients had recurrent reactions the were the a reduced grade than those after ~ the early dose. The typical onset that cutaneous symptom after the second dose (day 2; range, 1 to 3) was earlier than that after the an initial dose (Table 1).

Clinicians may not be all set to deal with delayed regional reactions to the mRNA-1273 vaccine. Provided the scale-up of mass inoculation campaigns throughout the world, these reactions are likely to create concerns among patients and requests for evaluation. These reactions have not been continuously recognized, guidance concerning the second dose that vaccine has varied, and many patients have unnecessarily obtained antibiotic agents. Us hope this letter encourages extr reporting and communication regarding the epidemiologic characteristics, causes, and implications of these delayed cutaneous reactions, because this information could allay the comes to of patients, encourage completion of vaccination, and minimize the unnecessary usage of antibiotic agents.

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Kimberly G. Blumenthal, M.D.Esther E. Freeman, M.D., Ph.D.Rebecca R. Saff, M.D., Ph.D.Lacey B. Robinson, M.D., M.P.H.Anna R. Wolfson, M.D.Ruth K. Foreman, M.D., Ph.D.Massachusetts basic Hospital, Boston, MA