Reactivation of Epstein-Barr Virus Following COVID-19 Vaccination

Epstein-Barr virus (EBV) is a common human herpesvirus that infects a majority of adults worldwide, typically transmitted through saliva during childhood. While most EBV infections are asymptomatic or cause mild symptoms, it can lead to conditions such as infectious mononucleosis (IM) in adolescents and young adults. Here we present two cases suggesting a potential link between EBV reactivation and COVID-19 vaccination. 

Case 1: EBV-Associated Lymphoproliferative Disorder:
A 79-year-old male presented with fever, pancytopenia, elevated liver enzyme levels, and other alarming laboratory findings two weeks after receiving the first dose of the BNT162b2 mRNA COVID-19 vaccine. Further investigations revealed EBV viremia localized in natural killer (NK) cells, suggesting a diagnosis of EBV-NK-LPD. Despite aggressive treatment attempts, the patient's condition worsened, and he succumbed to the disease two months later.

Case 2: Cutaneous Manifestations and EBV Reactivation:
A 24-year-old immunocompetent man experienced a scaly erythematous skin rash following the second dose of the COVID-19 vaccine. He tested positive for EBV reactivation, which is particularly noteworthy as previous cases of EBV reactivation after COVID-19 vaccination were primarily observed in immunosuppressed individuals. This case represents the first reported instance of EBV viral reactivation associated with cutaneous manifestations in an immunocompetent patient post COVID-19 vaccination.

The exact mechanisms and risk factors underlying EBV reactivation after COVID-19 vaccination remain unknown. However, it is important to raise awareness about this potential phenomenon to facilitate early diagnosis and appropriate management. These cases highlight the significance of considering EBV reactivation in the differential diagnosis for individuals presenting with unusual symptoms following vaccination.


Tanaka A, Kawaguchi T, Imadome KI, Hara S. [Epstein-Barr virus-associated lymphoproliferative disorders after BNT162b2 mRNA COVID-19 vaccination]. Rinsho Ketsueki. 2023;64(4):277-282. Japanese. doi: 10.11406/rinketsu.64.277. PMID: 37121772.

Herzum A, Trave I, D’Agostino F, Burlando M, Cozzani E, Parodi A. Epstein-Barr virus reactivation after COVID-19 vaccination in a young immunocompetent man: a case report. Clinical and Experimental Vaccine Research. 2022 May;11(2):222.


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