Epstein-Barr Virus Coinfection in COVID-19

Abstract

Epstein-Barr virus (EBV), a member of the herpes virus family, is a causative agent for infectious mononucleosis in young adults. It has an asymptomatic and subclinical distribution in about 90% to 95% of the world population based on seropositivity. EBV is associated with various lymphomas, nasopharyngeal carcinoma, and in immunocompromised states can give rise to aggressive lymphoproliferative disorders. Symptomatic patients mostly present with mild hepatitis, rash, oral symptoms, lymphadenopathy, and generalized malaise. Recently with the COVID-19 (coronavirus disease-2019) pandemic, hepatitis has been found to be related to acute EBV and cytomegalovirus reactivation versus acute infection in the absence of other major causes. We describe a case of EBV coinfection in a patient with resolving mild COVID-19 infection.

SARS‐CoV‐2 infection and lytic reactivation of herpesviruses: A potential threat in the postpandemic era?

“…Early in the COVID‐19 pandemic, several reports described cases of EBV and SARS‐CoV‐2 coinfection in patients. 35 , 36 Garcia‐Martinez et al reported reactivation of EBV with high viral loads in blood and plasma after SARS‐CoV‐2 infection in a 19‐year‐old French female patient with no other relevant clinical history. 37 A large survey of 50 419 samples from the United States collected between March and August 2020 showed much higher levels of EBV coinfection (2.13%) in the SARS‐CoV‐2 positive population compared to the coinfection rates of HSV (0.11%) and HCMV (0.07%).…”

Resurrecting Epstein–Barr Virus

“…The most important contribution of the Editor's choice article [1], however, is the early recognition of the pathogenetic role of EBV reactivation in patients with long-COVID. In fact, this had been reported by others in the course of acute infection [36][37][38] and variously interpreted as a possible coinfection or a correlate of disease severity or of immunodepression. The virus was detected either by serology (IgM anti-viral capsid-VCA) or by viral DNA quantitation.…”

“…It is recognized that reactivation may occur spontaneously [ 46 ] or following acute or chronic stress [ 59 ], and it is frequently observed in ICU patients [ 39 ], where it causes higher mortality. Therefore, it is not surprising that EBV markers of reactivation have been found in hospitalized cases of COVID-19 [ 36 , 37 , 38 , 60 ]. This makes sense since a worse outcome in COVID-19 is largely dependent on innate immunity failure, particularly inappropriate type I interferon production [ 23 , 36 , 61 , 62 ], and this dovetails with the immunodeficiencies predisposing to severe EBV infection [ 40 , 41 ], which mainly affect the innate immune system.…”

Machine learning assisted analysis on TCR profiling data from COVID-19-convalescent and healthy individuals unveils cross-reactivity between SARS-CoV-2 and a wide spectrum of pathogens and other diseases

“…Cellular cross-reactivity against EBV and SARS-CoV-2 has not been studied to date. However, there have been reports associating the clinical manifestation of COVID-19 with reactivation of EBV infection and correlating it with severe disease progression, thus underpinning a possible entanglement [70][71][72] . Cross-reactivity between SARS-CoV-2 and HIV has also been reported in studies describing false positive HIV results in COVID-19 patients.…”