Inflammation and Epstein–Barr Virus at the Crossroads of Multiple Sclerosis and Post-Acute Sequelae of COVID-19 Infection

Abstract

Recent studies have strengthened the evidence for Epstein–Barr Virus (EBV) as an important contributing factor in the development of multiple sclerosis (MS). Chronic inflammation is a key feature of MS. EBV+ B cells can express cytokines and exosomes that promote inflammation, and EBV is known to be reactivated through the upregulation of cellular inflammasomes. Inflammation is a possible cause of the breakdown of the blood–brain barrier (BBB), which allows the infiltration of lymphocytes into the central nervous system. Once resident, EBV+ or EBV-specific B cells could both plausibly exacerbate MS plaques through continued inflammatory processes, EBV reactivation, T cell exhaustion, and/or molecular mimicry. Another virus, SARS-CoV-2, the cause of COVID-19, is known to elicit a strong inflammatory response in infected and immune cells. COVID-19 is also associated with EBV reactivation, particularly in severely ill patients. Following viral clearance, continued inflammation may be a contributor to post-acute sequelae of COVID-19 infection (PASC). Evidence of aberrant cytokine activation in patients with PASC supports this hypothesis. If unaddressed, long-term inflammation could put patients at risk for reactivation of EBV. Determining mechanisms by which viruses can cause inflammation and finding treatments for reducing that inflammation may help reduce the disease burden for patients suffering from PASC, MS, and EBV diseases.