Double Trouble: Hemophagocytic Lymphohistiocytosis in a Recent COVID-19 Infection Associated With Epstein-Barr Virus (EBV) Reactivation

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome of excessive immune activation triggered by infections, malignancy, or genetic abnormalities. While the Epstein-Barr virus (EBV) is commonly associated with HLH, COVID-19 still lacks a well-defined association with this syndrome. This case describes a woman with a recent COVID-19 infection with the presumed reactivation of EBV, leading to fatality secondary to HLH. Initial suspicion was high for acute cholecystitis. However, multiple repeat imaging was negative, and the patient's rapid decline and constellation of laboratory results and symptoms are highly suggestive of a secondary HLH due to EBV reactivation. Re-elevation of EBV viral capsid antigen immunoglobulin G (IgG) antibody can be an indicator of EBV reactivation, and COVID-19 patients with EBV reactivation appear to have an increased risk of death. This case represents a novel presentation of secondary HLH. Further studies are needed to establish the role of antiviral therapies, such as ganciclovir, in treatment as well as to evaluate the prognostic value of early antiviral administration in COVID-19-reactivated herpesvirus infections, such as EBV. However, whether antiviral therapy may decrease mortality in HLH triggered by COVID-19-reactivated EBV infections warrants further investigation.