Literature review indicates recent EBV activity in two-thirds of long COVID patients — Evidence Review
Published in eLife, by researchers from Rutgers Health
Researched by
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Table of Contents
A new review suggests that co-infections, particularly Epstein-Barr virus (EBV) reactivation, may help explain persistent symptoms in people with long COVID. Most related research generally supports this hypothesis, with several studies linking EBV and other pathogens to long COVID symptoms and immune disruption, as highlighted in the recent eLife review.
- Multiple studies have found a higher prevalence of EBV reactivation in individuals with long COVID, with some reporting that two-thirds of affected patients show recent EBV activity, supporting the central idea of the new review 1 3 4.
- Broader literature also suggests that long COVID is likely a multifactorial syndrome, with evidence for persistent SARS-CoV-2 reservoirs, immune dysfunction, and reactivation of other latent viruses, consistent with the new study’s conclusions 2 5 7.
- Some studies indicate that interventions such as COVID-19 vaccination may moderate viral reactivation and alleviate symptoms, aligning with the suggestion that targeting co-infections could offer new therapeutic avenues for long COVID 11.
Study Overview and Key Findings
The emergence of long COVID as a widespread and often debilitating condition has raised ongoing questions about its underlying causes. While much research has focused on the direct effects of the coronavirus, this new review draws attention to the potential role of co-infections—latent or concurrent pathogens that may be reactivated or acquired during or after COVID-19 illness. By compiling evidence from a range of studies, the authors highlight a hypothesis that could broaden the scope of long COVID research and eventually inform more targeted treatments.
| Property | Value |
|---|---|
| Organization | Rutgers Health |
| Journal Name | eLife |
| Authors | Maria Laura Gennaro |
| Population | Individuals with long COVID |
| Methods | Literature Review |
| Outcome | Co-infections and their role in long COVID symptoms |
| Results | Two-thirds of long COVID patients showed recent EBV activity. |
Literature Review: Related Studies
We searched the Consensus paper database, which contains over 200 million research papers, to identify studies relevant to the link between co-infections (especially EBV) and long COVID. The following search queries were used:
- long COVID Epstein-Barr virus connection
- viral infections long COVID symptoms
- EBV activity long COVID patient outcomes
Summary Table of Topics and Key Findings
| Topic | Key Findings |
|---|---|
| How does EBV reactivation relate to long COVID symptoms? | - EBV reactivation is significantly more common in long COVID patients, with about two-thirds showing evidence of recent activity 1 3 4. - EBV reactivation correlates with fatigue, cognitive dysfunction, and other hallmark symptoms of long COVID 1 5. |
| What other infections or immune disruptions are linked to long COVID? | - Long COVID may involve persistent SARS-CoV-2 reservoirs, immune system dysregulation, and reactivation of multiple latent viral infections 2 3 7. - COVID-19 may also promote reactivation of other DNA viruses, with vaccination showing potential to reduce these effects 11. |
| What are the clinical characteristics and risk factors for long COVID? | - Long COVID manifests as a wide range of symptoms (fatigue, brain fog, dyspnea), often persisting for months and involving multiple organ systems 6 8 10. - Risk factors include female sex, higher BMI, older age, comorbidities, and more symptoms during initial infection 6 9. |
| Can targeting co-infections or immune pathways improve long COVID outcomes? | - COVID-19 vaccination may reduce the reactivation of latent viruses and alleviate some long COVID symptoms 11. - Therapies targeting the gut-brain axis or specific pathogens (e.g., antivirals, probiotics) are under consideration but lack definitive evidence 5 7. |
How does EBV reactivation relate to long COVID symptoms?
Several studies consistently report that reactivation of Epstein-Barr virus (EBV) is more common in individuals with long COVID than in those who recover without lingering symptoms. This phenomenon is observed both through serological markers and increased antibody responses, supporting the hypothesis that EBV reactivation may contribute to the characteristic fatigue, cognitive complaints, and other symptoms seen in long COVID.
- Observational studies find that around 66–67% of long COVID patients demonstrate recent EBV reactivation, compared to a much lower rate in those without persistent symptoms 1 3.
- Elevated EBV antibody levels in long COVID patients have been linked to increased severity and number of symptoms 1 3 4.
- EBV reactivation has specifically been associated with neurological symptoms and cognitive dysfunction in long COVID 5.
- Some research suggests that SARS-CoV-2-associated inflammation may trigger EBV reactivation, which could then perpetuate chronic symptoms 1 4.
What other infections or immune disruptions are linked to long COVID?
The literature indicates that long COVID is likely a multifaceted syndrome, potentially involving persistent SARS-CoV-2 infection, immune dysregulation, and reactivation of multiple latent viruses. There is emerging evidence that other pathogens (such as cytomegalovirus or tuberculosis) and disrupted immune responses play roles similar to EBV reactivation.
- Studies document broader immune perturbations in long COVID patients, including increased antibody responses to non-SARS-CoV-2 pathogens 2 3.
- Persistent viral reservoirs and immune dysregulation have been proposed as underlying mechanisms of long COVID 2 7.
- COVID-19 may facilitate the reactivation of other DNA viruses, and vaccination appears to reduce these viral reactivation events and associated symptoms 11.
- The new review builds on these findings by highlighting the concept of "immunity theft," where acute SARS-CoV-2 infection undermines immune control of other latent infections 2 11.
What are the clinical characteristics and risk factors for long COVID?
Long COVID is recognized as a syndrome with highly variable symptoms, often affecting multiple organ systems and lasting for months after the initial infection. Certain demographic and clinical factors appear to increase the risk of developing persistent symptoms.
- Fatigue, brain fog, breathlessness, and neurological symptoms are among the most common and persistent long COVID complaints 6 8 10.
- Risk factors for long COVID include female sex, older age, higher BMI, and experiencing multiple symptoms in the first week of acute infection 6 9.
- Some studies estimate that up to 80% of individuals recovering from COVID-19 experience at least one long-term symptom, though prevalence estimates vary 10.
- The diversity of symptoms has complicated efforts to identify universal biomarkers or treatments for long COVID 7 10.
Can targeting co-infections or immune pathways improve long COVID outcomes?
There is growing interest in whether addressing co-infections or modulating immune responses can help alleviate long COVID symptoms. Preliminary findings suggest that vaccination or therapies targeting specific pathogens may offer some benefit, but robust evidence from clinical trials is still lacking.
- A recent observational study found that COVID-19 vaccination is associated with reduced viral reactivation and fewer long COVID symptoms, suggesting a potential therapeutic effect 11.
- Interventions aimed at the gut-brain axis, such as probiotics or plant-based diets, have been proposed to help manage neurological and psychiatric symptoms of long COVID 5.
- The effectiveness of antibiotics, antivirals, or immune-modulating therapies in treating long COVID remains an open question and warrants further investigation 5 7.
- The new review underscores the need for clinical trials to test whether treating co-infections can directly improve long COVID outcomes 7 11.
Future Research Questions
Despite accumulating evidence, many questions remain about the mechanisms, risk factors, and optimal management of long COVID. Future research is needed to clarify causal relationships, evaluate potential therapies, and better understand the role of co-infections and immune dysregulation.
| Research Question | Relevance |
|---|---|
| Do treatments targeting Epstein-Barr virus improve long COVID symptoms? | Determining whether antiviral therapies against EBV can alleviate long COVID symptoms would clarify causality and guide clinical practice 1 3 5. |
| Which co-infections are most commonly associated with long COVID? | Identifying the spectrum of pathogens involved could improve diagnosis, risk assessment, and personalized treatment approaches for long COVID 2 4 11. |
| How does COVID-19 vaccination affect latent virus reactivation in long COVID patients? | Understanding the protective mechanisms of vaccination may inform immunization strategies for high-risk groups and help mitigate long COVID incidence 11. |
| What biomarkers can reliably distinguish long COVID from other post-viral syndromes? | Reliable biomarkers are needed for diagnosis, prognosis, and monitoring of treatment response, given the symptom overlap with other conditions 3 7 10. |
| Does treating latent tuberculosis or other infections impact long COVID progression? | Investigating the role of pathogens beyond EBV (such as TB) in long COVID could lead to broader treatment options and improved patient outcomes 2 7. |