On 1 March 2021, during cluster analysis of individual safety reports in the WHO global database VigiBase, two clusters of reports of delayed local adverse events were identified.
In 64 reports, lymphadenopathy localized in the ipsilateral axilla was reported, with a mean time to onset of the adverse event of 5 days.
In another cluster consisting of 605 reports, localized skin reactions were reported, including erythema and itching at the injection site, with a median time to onset of the adverse event of 7 days. Skin reactions may be a manifestation of a delayed-type hypersensitivity reaction.
Most of the recorded reactions were non-serious, and their occurrence is not a contraindication to administering subsequent doses of the vaccine.
Reports from VigiBase
Clustering was done by manufacturer for all vaccines for which more than 1000 safety reports were received (Pfizer-BioNTech, Moderna and AstraZeneca).
Cluster “delayed lymphadenopathies”
For the Moderna COVID-19 vaccine, cluster analysis identified a group of individual safety reports (n = 64) with the following manifestations: lymphadenopathy (n = 57, 89%), lymph node pain (n = 23, 36%), axillary pain (n = 22, 34%) and limb pain (n = 9, 14%). The average time to onset of the adverse event was five days. Ipsilateral lymphadenopathy a few days after vaccination was recorded most often.
Most cases were recorded after administration of the first dose of the vaccine. No cases required further treatment other than pain relief.
As of 1 March 2021, VigiBase contained 7 790 reports of cases of lymphadenopathy, including with the use of Moderna COVID-19 – 261 case, Pfizer-BioNTech – 6589, and AstraZeneca COVID-19 vaccine – 858.
Cluster “Delayed local skin reactions”
For the Moderna COVID-19 vaccine, a cluster (n = 605) was identified containing information on the following skin manifestations: erythema at the injection site (n = 489, 81%), swelling at the injection site (n = 325, 54%), itching at the injection site (n = 280, 46%), and a sensation of warmth at the injection site (n = 253, 42%). The median time to onset of these adverse events was seven days.
As of 1 March 2021, more than 4000 reports containing the above-mentioned manifestations after the use of all COVID-19 vaccines had been registered. A significant difference was recorded between the mean time to onset of the adverse event for the Moderna COVID-19 vaccine (six days) and the Pfizer-BioNTech and AstraZeneca vaccines (one day).
Discussion and conclusions
The pathophysiology of these reactions is unknown, but there are several mechanisms that may contribute to or cause them. The lymphadenopathy described in clinical studies was probably caused by a strong immune response. It may also be a manifestation of delayed-type hypersensitivity reactions. However, some hypersensitivity reactions are not immunologically mediated and may be caused by nonspecific irritation or a reaction to vaccine adjuvants.
A potential mechanism of local skin reactions (most often rash) is delayed-type hypersensitivity reactions, which may occur within hours or several weeks after vaccination.
In summary, this signal further outlines new characteristics of known adverse reactions, delayed ipsilateral lymphadenopathy and delayed local skin reaction to the Moderna COVID-19 vaccine.
Source of information: Signal assessment report “Delayed local adverse reactions and the Moderna Covid-19 vaccine”, Joseph Mitchell, MBBS, Uppsala Monitoring Centre, June 2021, based on data from the WHO Global Database – VigiBase
