Risk of lymphadenopathy from SARS-CoV-2 vaccination: a self-controlled case series analysis

OBJECTIVESTo assess the risk of lymphadenopathy following SARS-CoV-2 vaccination. METHODSA self-controlled case series design was used to determine whether the risk of lymphadenopathy was higher in the 1- to 42-day risk interval after COVID-19 vaccination compared to the control period. In addition, subgroup analyses were conducted according to baseline characteristics, time since vaccination, and sensitivity analyses adjusted for the length of the risk interval. RESULTSThe risk of developing lymphadenopathy in the risk interval (1-42 days) after COVID-19 vaccination compared to the control period was significantly increased, with a relative incidence (RI) of 1.17 (95% CI, 1.17-1.18) when the first, second, and third doses were combined. The RI was greater on the day of vaccination (1.47; 95% CI, 1.44-1.50). In subgroup analyses by baseline characteristics, a significantly increased risk or trend toward increased risk was observed in most subgroups except for those aged 70 years and older, with a significant increase in risk in younger individuals, those with a Charlson’s comorbidity index <5, and those who received mRNA vaccines (mRNA-1273 > BNT162b2). Within the 1- to 42-day post-dose risk period, the relative risk was highest during the 1- to 7-day post-dose period (1.59; 95% CI, 1.57-1.60) compared to the control period, and then the risk declined. In the sensitivity analysis, we found that the longer the risk window, the smaller the RI. CONCLUSIONSSARS-CoV-2 vaccination is associated with a statistically significant increase in the risk of lymphadenopathy, and this risk was observed only with mRNA vaccines.