Multifocal lymphadenopathies with polyclonal reactions primed after EBV infection in a mRNA-1273 vaccine recipient.

We report a case of recurrent tender, multifocal lymphadenopathies associated with B-symptoms, clinically mimicking lymphoma in a mRNA-1273 vaccine recipient after a recent Epstein-Barr virus (EBV) infection. In the lymph node biopsy, monocytoid B-cell hyperplasia, TH2 (GATA3+) predominance, and hyperplasia of interferon-gamma-producing plasmacytoid dendritic cells were observed along with sustained neutralising antibody production against SARS-CoV-2 wild-type and five variants. High titres of anti-S antibodies and neutralising antibodies were observed, excepted for variant B.1.529** (omicron) and B.1.351** (beta), due to several mutations in the spike protein, including the E484K mutation. We postulated that EBV acted as an immunological enhancer with the mRNA-1273 vaccine, inducing a sustained inflammatory response over several weeks. However, the polyclonal nature of the lymphadenopathy with polytypic plasmacytosis and pseudo-tumoural reaction cell hyperplasia were associated with failure to mount acute phase responses.