In January 2021, the European Medicines Agency (EMA) authorized use of the viral vector COVID-19 vaccine Vaxzevria (ChAdOx1-S) in the European Union. Given the scale-up of mass vaccination campaigns across the world, it is likely that new adverse reactions will occur that were not reported in the initial trials.
We have observed a delayed large local skin reaction to the first dose of Vaxzevria in a 62-year-old, white female. Except for cat allergy, no history of allergy was reported. Following the resolution of initial local and systemic symptoms after vaccination, the delayed reaction had an onset on day 10 that appeared near the injection site. The appearance of the reaction was an erythema with a maximum diameter of 10 cm on day 14 after vaccination (Figure 1). Considerable induration and pain near the injection site was reported. Besides the local erythema, no further cutaneous symptoms in other localizations were observed. The symptoms cleared up after 15 days and fully resolved over the following 3 days. No systemic symptoms occurred with delayed local reaction. The patient did not require treatment for reaction. A biopsy was not performed.
The complete post-vaccination course was as follows: On day 0, the vaccination with Vaxzevria took place and no immediate reaction to the vaccine was observed. On day 1 after vaccination, the patient reported elevated temperature, malaise, and fatigue. The symptoms of systemic reaction resolved on day 2, but a slight soreness near the injection site was reported. On day 3, an erythema with 5 cm diameter, warmth and swelling was observed near injection site. On days 4-6, local symptoms remitted and completely resolved on day 7-9 except for a palpable nodule in the deep soft tissue. On day 10, a new erythema recurred near injection site and spread to a maximum diameter of 10 cm on days 11-14, accompanied by a large, localized swelling and induration. From day 15, the erythema was regressive and had completely resolved by day 18. Photographs show the skin reaction over time with varied size and severity of the local findings between day 10 and 14 (Figure 1).
In the Vaxzevria clinical trials, a delayed local large reaction to the vaccine has not been described. In the phase 1/2 trial of Vaxzevria, local site reactions were only recorded for 7 days following vaccination.1 It is therefore possible that the observation period was too short to report the delayed injection site reactions. Likewise, in the interim primary efficacy analysis of four phase 3 randomized controlled trials of ChAdOx1-S, no case with delayed cutaneous reaction was reported.2
On the other hand, a similar phenomenon as in our patient has been described multiple times for the mRNA-based Moderna (mRNA-1273) vaccine and to lesser extent for Comirnaty (Pfizer/BioNTech, BNT162b2).3-5 In the Moderna phase 3 trial, delayed injection site reaction occurred in 244 (0·8%) participants after the first dose of Moderna vaccine and in 68 (0 2%) participants after the second dose.3 The delayed injection site reaction was defined as reaction on or after day 8.
The International COVID-19 Dermatology Registry has started capturing skin reactions to COVID-19 vaccines in January 2021 and just recently published 414 cases with skin reactions to Comirnaty and Moderna vaccines.5 They defined delayed large local reactions as occurrence after 4 or more days after vaccination. The most common cutaneous reaction to Moderna vaccination was delayed large local reactions (n=175 first dose, n=31 second dose). Interestingly, they also reported cases with local large reaction after administration of Comirnaty (n=5 first dose, n=7 second dose). Of note, no cases of anaphylaxis or other serious adverse events after subsequent vaccination following delayed major local reactions to Moderna or Comirnaty vaccines were described.5
The time course and clinical symptoms of delayed major skin reaction after vaccination with Moderna or Comirnaty have a similar pattern that we recognized in our patient after Vaxzevria vaccination. To the best of our knowledge, this is the first description of a patient with delayed large local reaction to the vector-based Vaxzevria vaccine.
We suspect a delayed-type or T-cell-mediated hypersensitivity reaction as it was proposed for the mRNA vaccines.4 A skin-biopsy specimen obtained from a patient with delayed large local reaction after Moderna vaccination showed findings consistent with delayed-type or T-cell-mediated hypersensitivity, supporting this hypothesis.4 Although the aetiology of these reactions is unclear, delayed-type hypersensitivity reactions to excipient-ingredients of vaccines have been reported previously.5
Given that neither local injection site reactions nor delayed-type hypersensitivity reactions are contraindications to subsequent vaccination, our patient was encouraged to receive the second dose of Vaxzevria to complete her vaccination course. With this correspondence, we would like to raise awareness about delayed injection site reactions occurring also after viral vector vaccines against SARS-CoV-2 and hope to encourage additional reporting and patient education regarding the cutaneous reactions after COVID-19 vaccination.