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With the increasing number of vaccinations, COVID-19 vaccine-associated lymphadenopathy (C19-VAL) has been frequently reported. Current findings emphasize the characteristics of C19-VAL. The mechanism of C19-VAL is complicated to explore. Accumulated reports separately show that C19-VAL incidence is associated with receiver age and gender, reactive change within lymph nodes (LN), etc. We constructed a systematic review to evaluate the associated elements of C19-VAL and provide the mechanism of C19-VAL. Articles were searched from PubMed, Web of Science and EMBASE by using the processing of PRISMA. The search terms included combinations of the COVID-19 vaccine, COVID-19 vaccination and lymphadenopathy. Finally, sixty-two articles have been included in this study. Our results show that days post-vaccination and B cell germinal center response are negatively correlated with C19-VAL incidence. The reactive change within LN is highly related to C19-VAL development. The study results suggested that strong vaccine immune response may contribute to the C19-VAL development and perhaps through the B cell germinal center response post vaccination. From the perspective of imaging interpretation, it is important to carefully distinguish reactive lymph nodes from metastatic lymph node enlargement through medical history collection or evaluation, especially in patients with underlying malignancy.<\/jats:p>","DOI":"10.3390\/vaccines11030696","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T05:46:42Z","timestamp":1679291202000},"page":"696","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Immune Response Related to Lymphadenopathy Post COVID-19 Vaccination"],"prefix":"10.3390","volume":"11","author":[{"given":"Tzu-Chuan","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Hueng-Yuan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Chuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"},{"name":"School of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Neuroscience Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Department of Electrical Engineering, I-Shou University, Kaohsiung 840, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9741-5824","authenticated-orcid":false,"given":"Hung-Pin","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3973-8390","authenticated-orcid":false,"given":"Kuo-Pin","family":"Chuang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 912, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Hui","family":"Yuan","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Laboratory, Department of Chemistry, National University of Singapore, Singapore 119077, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciao-Ning","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5856-0498","authenticated-orcid":false,"given":"Ming-Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan"},{"name":"Center of General Education, Shu-Zen Junior College of Medicine and Management, Kaohsiung 821, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1917-5893","authenticated-orcid":false,"given":"Yu-Chang","family":"Tyan","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 912, Taiwan"},{"name":"Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"},{"name":"Center for Tropical Medicine and Infectious Disease Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"ref_1","unstructured":"Mathieu, E., Ritchie, H., Rod\u00e9s-Guirao, L., Appel, C., Giattino, C., Hasell, J., Macdonald, B., Dattani, S., Beltekian, D., and Ortiz-Ospina, E. 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