A sigh of relief: vaccine-associated hypermetabolic lymphadenopathy following the third COVID-19 vaccine dose is short in duration and uncommonly interferes with the interpretation of [F]FDG PET-CT studies performed in oncologic patients.

Purpose: The incidence of COVID-19 vaccine-associated hypermetabolic lymphadenopathy (VAHL) is high following the administration of the first and second BNT162b2 vaccine doses. The impact of this finding on [F]FDG PET-CT interpretation and its correlation with the induced humoral immunity have been reported. Assuming the amnestic immune response is different following the third vaccine dose, we aimed to explore the incidence of VAHL over time after the third BNT162b2 dose administration, and its relevance to [F]FDG PET-CT interpretation in oncologic patients.

Methods: A total of 179 consecutive oncologic patients that underwent [F]FDG PET-CT after a third BNT162b2 vaccine dose were included. The presence of VAHL was assessed. On VAHL-positive scans, the SUVmax, number, location, and size of the "hot" nodes were recorded. The median time interval between vaccination and imaging was 8 (IQR, 5-14) days.

Results: The incidences of all-grade VAHL and grade 3-4 VAHL were 47.5% and 8.9%, respectively. VAHL was identified on 82.5% of studies performed within the first 5 days from vaccination. Grade 3-4 VAHL was observed on 28.1% of studies performed within the first 5 days from vaccination, but was not detected on studies performed more than 5 days from vaccination. Separation between VAHL and malignant lymphadenopathy was not possible in only 2 of the 179 study patients. On a multivariable logistic regression, independent predictors of grade 3-4 VAHL were short time interval between vaccination and imaging (Pv < 0.01), younger age (Pv < 0.01), and lower BMI (Pv = 0.03).

Conclusion: VAHL is commonly identified on [F]FDG PET-CT performed within the first 5 days from the third BNT162b2 vaccine dose administration. High-grade VAHL is unlikely to be observed on a scan performed 6 days or longer from vaccination, and is even less likely in older and obese patients.