Unveiling the mysterious contribution of epstein-barr virus and severe acute respiratory syndrome coronavirus-2 in neurological manifestations

Abstract

EBV or human herpesvirus 4 is omnipresent, known to infect ~90% of the worldwide adult population, albeit only a few individuals develop EBV-linked diseases [1]. In general, EBV is associated with various malignancies like Burkitt's lymphoma, nasal natural killer (NK) cell lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma, etc [2–6]. EBV is also associated with a variety of neural ailments, including multiple sclerosis (MS), Alzheimer's disease (AD), cerebellar ataxia, meningoencephalitis, cranial nerve palsies, and Guillain-Barré syndrome [7–9]. It is predicted that >25% of EBV infected patients have cerebrospinal fluid (CSF) anomalies. Numerous epidemiological, virological, and clinical studies support the involvement of EBV in MS [10,11]. Studies establish the correlation of infectious mononucleosis (IM) and MS cases, with both diseases showing epidemiological similarities [12]. Several studies suggest EBV infection favors the development of MS disease pathology; however, some studies question the association [13]. Moreover, EBV has been shown to infect neurons [14], glial cells [15] and endothelial cells [16] which are the key components of the blood brain barrier (BBB). Upon infection EBV can modulate the neural homeostasis by inducing or suppressing the inflammatory reactions. Thus, the involvement of EBV in disease pathogenesis needs to be evaluated. Some of the popular hypotheses that explain EBV as an MS pathogenesis trigger were studied here.