SARS-CoV-2 and EBV; the cost of a second mitochondrial “whammy”?

Abstract

We, and others, have suggested that as the SARS-CoV-2 virus may modulate mitochondrial function, good mitochondrial reserve and health could be key in determining disease severity when exposed to this virus, as the immune system itself is dependent on this organelle’s function. With the recent publication of a paper showing that long COVID could be associated with the reactivation of the Epstein Barr Virus, which is well known to manipulate mitochondria, we suggest that this could represent a second mitochondrial “whammy” that might support the mitochondrial hypothesis underlying COVID-19 severity and potentially, the occurrence of longer-term symptoms. As mitochondrial function declines with age, this could be an important factor in why older populations are more susceptible. Key factors which ensure optimal mitochondrial health are generally those that ensure healthy ageing, such as a good lifestyle with plenty of physical activity. The ability of viruses to manipulate mitochondrial function is well described, and it is now also thought that for evolutionary reasons, they also manipulate the ageing process. Given that slowing the ageing process could well be linked to better economic outcomes, the link between mitochondrial health, economics, COVID-19 and other viruses, as well as lifestyle, needs to be considered.

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

“…Because of the effects of long COVID‐19 44 and EBV reactivation 45 on mitochondrial functions that are important to host immune response, Nunn et al suggested that EBV reactivation in patients with long COVID might represent a second mitochondrial “hit” that promotes occurrence of longer‐term symptoms. 46 Another recent study reported a similar finding of significant levels of EBV viremia in critically ill COVID‐19 patients (78% of COVID‐19 patients vs. 44.4% of non‐COVID‐19 patients) and associated the high prevalence of EBV reactivation in COVID‐19 patients with the inflammatory factor, IL‐6. 41 In a different mechanistic study, Verma et al indicated a role for lytic infection of EBV in increasing the susceptibility of SARS‐CoV‐2 infection of human oral epithelium by upregulating ACE2 expression.…”

“…Recent studies have begun to address the mechanisms underlying the interactions between SARS‐CoV‐2 and EBV. Because of the effects of long COVID‐19 44 and EBV reactivation 45 on mitochondrial functions that are important to host immune response, Nunn et al suggested that EBV reactivation in patients with long COVID might represent a second mitochondrial “hit” that promotes occurrence of longer‐term symptoms 46 . Another recent study reported a similar finding of significant levels of EBV viremia in critically ill COVID‐19 patients (78% of COVID‐19 patients vs. 44.4% of non‐COVID‐19 patients) and associated the high prevalence of EBV reactivation in COVID‐19 patients with the inflammatory factor, IL‐6 41 .…”

Herpesvirus infections and post-COVID-19 manifestations: a pilot observational study

“…New data regularly appear in the modern references, which also confirms the significant role of reactivated herpesviruses and primarily EBV in the formation of post-COVID disorders, which coincides with the results of our work. Indeed, a study by Jeffrey E. Gold et al, consisting of 185 patients with COVID-19, found that the prevalence of long-term symptoms of COVID-19 accounted for 30.3% (56/185), including four asymptomatic patients with COVID-19 [ 31 , 32 ]. EBV reactivation was detected (based on the determination of early antigen-diffusion IgG (EA-D) or capsid IgM (VCA) EBV antigens) in 66.7% of patients with long-term COVID-19 at the onset of the disease ( p < 0.001), and in 18 people—21–90 days after a positive COVID-19 test, indicating EBV reactivation shortly after or at the time of COVID-19 infection.…”

Epstein–Barr virus and COVID‐19

“… 10 , 11 Furthermore, altered metabolic profile and mitochondrial biogenesis in both viruses 10 can result in a sustained inflammatory response in SARS‐CoV‐2 and may mount EBV‐induced fatigue in an already compromised individual. 12 These would allow resurfacing of an otherwise latent EBV infection that may reside asymptomatically in its host.…”