Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue, 2021, Wyller

[Multiple mentions of chronic fatigue syndrome but is a chronic fatigue study]

Background: Epstein-Barr virus (EBV) causes infectious mononucleosis (IM) that can lead to chronic fatigue syndrome. The CEBA-project (Chronic fatigue following acute EBV infection in Adolescents) has followed 200 patients with IM and here we present an immunological profiling of adolescents with IM related to clinical characteristics.

Methods: Patients were sampled within 6 weeks of debut of symptoms and after 6 months. Peripheral blood mononuclear cells (PBMC) were cultured and stimulated in vitro (n=68), and supernatants analyzed for cytokine release. Plasma was analyzed for inflammatory markers (n=200). The Chalder Fatigue Questionnaire diagnosed patients with and without chronic fatigue at 6 months (CF+ and CF- group, respectively) (n=32 and n=91, in vitro and plasma cohorts, respectively.

Results: Broad activation of PBMC at baseline, with high levels of RANTES (Regulated on activation, normal T-cell expressed and secreted) in the CF+ group, and broad inflammatory response in plasma with high levels of T-cell markers was obeserved. At 6 months, there was an increased β-agonist response and RANTES was still elevated in cultures from the CF+ group. Plasma showed decrease of inflammatory markers except for CRP which was consistently elevated in the CF+ group.

Conclusion: Patients developing chronic fatigue after IM have signs of T-cell activation and low-grade chronic inflammation at baseline and after 6 months.

Open access, https://www.frontiersin.org/articles/10.3389/fimmu.2021.715102/full

 

This looks like a potentially useful study to me. It suggests the development of chronic fatigue is related to T cell activity.

 

Quotes Hickie et al 2006 to support the claim that: "Fatigue is a particularly prominent feature of acute EBV infection and can last for months and even develop into Chronic Fatigue Syndrome" - Hickie et al looked at EBV, Q fever and Ross River fever, in 253 subjects 28 of whom were classed as having CFS = post-infective fatigue syndrome at 6 months and 12 months post infection - these comprised 5 x EBV, 3 Qf, 13 x RRf and 8 x uc, one of these was excluded at 6 months. PEM was not included in the CFS criteria. An interesting feature was that the 28 were 50/50 male/female.

I'm not sure that 5 cases in one study is enough data on which to base the claim that post EBV fatigue develops into CFS. The definitional boundary between post infective syndromes - involving fatigue or otherwise - and ME/CFS are too fuzzy to talk with certainty about one developing into the other.