Original article
Vol. 152 No. 2122 (2022)
Multifocal lymphadenopathies with polyclonal reactions primed after EBV infection in a mRNA-1273 vaccine recipient
- François R. Girardin
- Alexandar Tzankov
- Giuseppe Pantaleo
- Françoise Livio
- Gilbert Greub
Summary
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.
References
- Hagen C, Nowack M, Messerli M, Saro F, Mangold F, Bode PK. Fine needle aspiration in COVID-19 vaccine-associated lymphadenopathy. Swiss Med Wkly. 2021 Jul;151:w20557. https://doi.org/10.4414/smw.2021.20557
- Barda N, Dagan N, Ben-Shlomo Y, Kepten E, Waxman J, Ohana R, et al. Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting. N Engl J Med. 2021 Sep;385(12):1078–90. https://doi.org/10.1056/NEJMoa2110475
- Brosh-Nissimov T, Sorek N, Yeshayahu M, Zherebovich I, Elmaliach M, Cahan A, et al. Oropharyngeal shedding of herpesviruses before and after BNT162b2 mRNA vaccination against COVID-19. Vaccine. 2021 Sep;39(40):5729–31. https://doi.org/10.1016/j.vaccine.2021.08.088
- Brewer KD, DeBay DR, Dude I, Davis C, Lake K, Parsons C, et al. Using lymph node swelling as a potential biomarker for successful vaccination. Oncotarget. 2016 Jun;7(24):35655–69. https://doi.org/10.18632/oncotarget.9580
- Hartsock RJ. Postvaccinial lymphadenitis. Hyperplasia of lymphoid tissue that simulates malignant lymphomas. Cancer. 1968 Apr;21(4):632–49. https://doi.org/10.1002/1097-0142(196804)21:4<632::AID-CNCR2820210415>3.0.CO;2-O
- Dorfman RF, Herweg JC. Live, attenuated measles virus vaccine. Inguinal lymphadenopathy complicating administration. JAMA. 1966 Oct;198(3):320–1. https://doi.org/10.1001/jama.1966.03110160148051
- Hendry AJ, Dey A, Beard FH, Khandaker G, Hill R, Macartney KK. Adverse events following immunisation with bacille Calmette-Guérin vaccination: baseline data to inform monitoring in Australia following introduction of new unregistered BCG vaccine. Commun Dis Intell Q Rep. 2016 Dec;40(4):E470–4.
- Kanda T, Yajima M, Ikuta K. Epstein-Barr virus strain variation and cancer. Cancer Sci. 2019 Apr;110(4):1132–9. https://doi.org/10.1111/cas.13954
- Steeper TA, Horwitz CA, Ablashi DV, Salahuddin SZ, Saxinger C, Saltzman R, et al. The spectrum of clinical and laboratory findings resulting from human herpesvirus-6 (HHV-6) in patients with mononucleosis-like illnesses not resulting from Epstein-Barr virus or cytomegalovirus. Am J Clin Pathol. 1990 Jun;93(6):776–83. https://doi.org/10.1093/ajcp/93.6.776
- Fenwick C, Croxatto A, Coste AT, Pojer F, André C, Pellaton C, et al. Changes in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies. J Virol. 2021 Jan;95(3):e01828–20. https://doi.org/10.1128/JVI.01828-20