Purpose: COVID-19 vaccine-induced reactive axillary lymph nodes (RAL) on fluorodeoxyglucose (FDG) PET/computed tomography (CT) imaging can mimic malignant lymphadenopathy, leading to diagnostic errors. Reported RAL prevalence varies widely in the literature, and factors contributing to its development remain poorly understood. This meta-analysis aims to evaluate vaccine-induced RAL observed on FDG PET/CT imaging and consolidate evidence from multiple studies to assess its prevalence, duration, and associations with vaccine-related factors and demographic characteristics.

Method: Using multiple databases, a systematic review and meta-analysis was conducted on studies reporting RAL on FDG PET/CT following COVID-19 vaccination. The primary outcome was RAL prevalence, while the secondary outcomes were maximum standardized uptake value (SUVmax), vaccine-to-scan interval, and associations with vaccine type and demographics.

Results: A total of 25 studies comprising of 5010 subjects were included. Mean SUVmax of reactive nodes was 2.8 ± 1.2. Overall, RAL prevalence was 38.6% ± 17.6, higher in females (58.1% versus 41.9%, P = 0.02) and younger individuals (mean age 63.3 versus 70.7 years, P = 0.03). The RAL rate was not statistically different between mRNA (39.9% ± 16.9) and non-mRNA vaccines (26.3% ± 30.9). However, subanalysis showed about 40% RAL with Pfizer and Moderna mRNA vaccines and AstraZeneca non-mRNA vaccine, versus much lower, below 20%, RAL with Sinovac and Johnson & Johnson non-mRNA vaccines. Stricter PET/CT interpretation criteria using blood pool threshold reduced RAL prevalence to <20%. RAL rate declined with time but was still present after 1 month.

Conclusion: Low activity RAL is common on FDG PET/CT after COVID-19 vaccination, while higher activity RAL (above blood pool) that can lead to clinical errors is less frequent. The frequency of RAL is affected by expected factors, such as age, gender, vaccine type, and time after vaccination, which indirectly suggest the link between RAL and COVID-19 postvaccinal immunity.