Can viral infections, such as Epstein-Barr (EBV) virus, trigger chronic fatigue syndrome?

Viral Infections Can Trigger Chronic Fatigue Syndrome

Yes, viral infections, including Epstein-Barr virus (EBV), can trigger chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME/CFS). The evidence strongly supports a causal relationship between certain viral infections and the subsequent development of chronic fatigue syndrome in susceptible individuals.

Viral Triggers for ME/CFS

• A wide range of pathogens have been documented to cause ME/CFS onset, including:

  • Epstein-Barr virus (EBV)
  • SARS-CoV-2 (COVID-19)
  • SARS-CoV (original SARS)
  • Coxiella burnetii (Q fever)
  • Ross River virus
  • West Nile virus 1

• In one notable study, 27.1% of SARS-CoV infection survivors met the criteria for ME/CFS diagnosis 4 years after their initial infection 1

• Many cases of ME/CFS begin with a sudden onset following an acute, presumably viral illness, with subsequent recurrent "flu-like" symptoms 2

Pathophysiological Mechanisms

The relationship between viral infections and ME/CFS involves several potential mechanisms:

1. Immune Dysregulation:

   • Viral infections can trigger persistent immune abnormalities including:
     • Diminished natural killer cell function
     • T cell exhaustion and other T cell abnormalities
     • Reactivation of latent herpesviruses 1

2. Mitochondrial Dysfunction:

   • Viral infections can lead to:
     • Altered fatty acid metabolism
     • Dysfunctional mitochondrion-dependent lipid catabolism
     • Redox imbalance 1

3. Neuroinflammation:

   • Extensive neuroinflammation
   • Cerebral blood flow abnormalities
   • Brainstem abnormalities 1

4. Viral Persistence or Reactivation:

   • Reactivation of herpesviruses (including EBV, HHV-6, HHV-7, and cytomegalovirus) is associated with ME/CFS 1

Diagnostic Criteria for ME/CFS

ME/CFS is defined by:

• "Substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities" for at least 6 months
• Profound fatigue not alleviated by rest
• Post-exertional malaise
• Unrefreshing sleep
• Cognitive impairment or orthostatic intolerance (or both) 1, 3

Clinical Implications

• Up to 75% of people with ME/CFS cannot work full-time
• 25% have severe ME/CFS, often meaning they are bed-bound, have extreme sensitivity to sensory input, and are dependent on others for care 1
• Around half of individuals with long COVID meet the criteria for ME/CFS 1

Management Approaches

For patients with suspected post-viral ME/CFS:

1. First-line treatments:

   • Cognitive Behavioral Therapy (CBT) has strong evidence for improving health function, quality of life, and physical function 3
   • Mindfulness-based therapies show small to moderate improvements in quality of life 3

2. For pain management:

   • Serotonin-norepinephrine reuptake inhibitors (SNRIs) and pregabalin may be considered for pain-predominant symptoms 3
   • Manual acupuncture may benefit patients with fibromyalgia-like symptoms 3

3. Important cautions:

   • Graded exercise therapy is no longer recommended and may worsen symptoms 3
   • NSAIDs should be avoided for chronic pain related to CFS due to lack of efficacy and potential harm 3

Key Considerations

• Viral serologies alone are not consistently useful in evaluating patients presenting with chronic fatigue 4
• The major hypothesis of ME/CFS pathogenesis is that infectious agents such as viruses may trigger and lead to chronic activation of the immune system with abnormal regulation of cytokine production 5
• Patients with suspected ME/CFS should be referred to a specialist with experience in ME/CFS for diagnosis and initial treatment 3

While early studies questioned the etiological relationship between EBV and CFS 6, more recent comprehensive research has established strong links between viral infections and the development of ME/CFS, with multiple pathophysiological mechanisms now identified 1.