COVID-19 Vaccination Associated with Higher Incidence of DLLR in Women

Toshihide Higashino, MD, PhD

According to a new cross-sectional study from Japan, the initial dose of the SARS-CoV-2 mRNA-1273 vaccine was associated with a higher incidence of delayed large local reactions (DLLR) in female patients and individuals 30-96 years old, which suggested a type IV allergic skin reaction due to the vaccine.

Instances of DLLR- which typically manifest 7 days after vaccination and persists for roughly 4 days- have occurred following vaccination against COVID-19 with the Moderna vaccine, and have been referred to as “COVID arm” and “Moderna arm” in the United States and Japan, respectively.

Despite being rare, little is known regarding the pathophysiology of DLLR following COVID-19 vaccination.

In this retrospective cross-sectional study, an investigative team led by Toshihide Higashino, MD, PhD, of the Department of Dermatology at Self-Defense Forces Central Hospital, analyzed medical examination data in a large-scale population in Japan to assess the associations of sec and age with susceptibility to DLLR.

Eligible participants received their second dose of the COVID-19 vaccine after receiving the first dose of the same vaccine 4-6 weeks earlier, and were interviews by 5 dermatologists from the investigative team to assess adverse skin reactions to the first dose at the Self-Defense Forces large-scale vaccination center in Tokyo. These assessments occurred from May 24 to November 30, 2021.

Delayed large local reactions were considered if a participant reported erythema, tenderness, itchiness, induration, burning sensation, or swelling around the injection site that were noted on or after the sixth day after injection following a patient’s first vaccination.

The incidence rate of DLLR stratified by sex and age group was the primary outcome of the study, and odds ratios (ORs) were calculated to evaluate the differences between groups. Meanwhile, multiple linear regression analyses were conducted to evaluate the association between the time of onset and duration of DLLR.

Among the 650,532 recipients of the second dose that were featured in the large-scale vaccination center population. 5893 were interviewed. Among these recipients, 56.3% were male and 43.7% were female, with the median age being 55 and 50 years old, respectively.

The incidence rate of DLLR was significantly higher among female participants (22.4%) than males (5.1%). Generally speaking, the incidence rate was also significantly higher in patients 30-39 years old (14.3%), 40-49 years (15.8%), 50-59 (14.9%), and 60-69 years (12.6%), when compared to patients 18-29 years.

The mean time of onset was significantly earlier among males (6.97 days) than females (7.32) after adjusting for age (P=.005). However, the mean duration of symptoms was significantly shorter among males (4.83 days).

"The association between demographic characteristics and susceptibility of DLLR suggests that the condition is a type IV allergic skin reaction," the team wrote.

The study, "Assessment of Delayed Large Local Reactions After the First Dose of the SARS-CoV-2 mRNA-1273 Vaccine in Japan," was published online in JAMA Dermatology.