Key points:
- 30% of ME/CFS cases associated with an infection are thought to be due to Epstein–Barr virus (EBV) – but not everyone who has an EBV infection develops ME/CFS.
- Researchers in America have designed an ongoing study to investigate why this might be the case.
- Early findings show that compared with those who recovered from EBV, those who went on to meet criteria for ME/CFS had:
- Lower levels of molecules that facilitate communication between cells of the immune system and other cells in the body (cytokines), specifically interleukin-5 and interleukin-13.
- More dense and less flexible networks of cytokines which may have prevented full recovery from the EBV infection.
- The study is ongoing, and there are many areas which are still to be investigated including genetic, cognitive, and sex-related factors.
- The researchers highlight the need for the investigation of factors increasing the risk of development of post viral fatigue after other infections such as COVID-19, Dengue, and West Nile.
Background
The majority of people with ME/CFS report an infectious illnesses before the onset of the disease, and a survey by the European ME Alliance, found that 58% of respondents associated the onset of their ME/CFS with an “infectious disease”.
Approximately 30% of the ME/CFS cases associated with an infection are thought to be due to infectious mononucleosis – glandular fever, caused by the Epstein–Barr virus (EBV) – but not everyone who has an EBV infection develops ME/CFS.
What did the study do?
A study published in the journal ‘Microorganisms, by Professor Leonard Jason and colleague Ben Katz aimed to investigate why some people who have an EBV are more likely to develop ME/CFS than others – importantly, the researchers used a study design which recruited participants before they caught EBV, and followed them up over time.
The Depaul symptom questionnaire (DSQ) was used to assess:
- Sociodemographic, medical, occupational, and social history.
- Self-report measure of ME/CFS symptomatology and illness.
The DSQ is said to provide a standardised method for assessing various case definitions of ME/CFS, including Fukuda (for CFS), Canadian Consensus Criteria, and the Institute of Medicine (IOM) criteria.
What did the findings show?
Of the 4,501 participants in the study, 238 (5%) developed infectious mononucleosis.
Six months after infection, 157 (66%) no longer had symptoms and 81(34%) had ongoing symptoms.
Of the 81 participants with ongoing symptoms:
- 55 (68%) met criteria for ME/CFS.
- 35 (64%) met one ME/CFS case definition.
- 20 (36%) met more than one ME/CFS case definition.
- 26 (32%) did not meet criteria for ME/CFS.
Regrettably, the exact criteria the participants met was not specified by the researchers in the article.
Results showed that compared with those that recovered, those who went on to meet criteria for ME/CFS following infectious mononucleosis had lower levels of proteins called cytokines – molecules that facilitate communication between cells of the immune system and other cells in the body, specifically interleukin-5 (IL-5) and interleukin-13 (IL-13).
Interestingly, IL-5 is involved in the production of anti-inflammatory B1 cells, and according to Jason and Katz, impaired B1 cells have been linked with other illnesses such as multiple sclerosis, lupus, and rheumatoid arthritis.
Participants who went on to meet criteria for ME/CFS also demonstrated more dense and less flexible networks of cytokines. The researchers noted that it may be this lack flexibility in cytokine networks that meant the participants who went on to develop ME/CFS were unable to “cope successfully with the primary EBV infection”. Notably, cytokine networks are thought to drive disease processes such as inflammatory bowel disease.
The study by Jason and Katz is ongoing, and the researchers state that there are many areas which are still to be investigated including genetic, cognitive, and sex-related factors. The researchers also highlight the need for the investigation of factors increasing the risk of development of post viral fatigue after other infections such as COVID-19, Dengue, and West Nile.
What are the strengths and limitations of this study?
- Rather than relying on pre-existing data that was not collected for their specific research question or recruiting participants with ME/CFS and assessing whether or not they had a history of EBV infection, Jason and Katz recruited participants before EBV infection and followed them up over time – this enabled the researchers to be sure that the EBV infection occurred before the onset of ME/CFS.
- Although the Fukuda (for CFS), Canadian Consensus Criteria, and the Institute of Medicine (IOM) criteria were mentioned, the researchers did not clearly state which ME/CFS criteria the participants were assessed using. It is possible that some of the participants meeting only one ME/CFS criteria only met the Fukuda criteria for CFS which does not require the presence of post exertional malaise for a diagnosis to be made. It would be important to consider whether there were differences between those who met different diagnostic criteria.
- The participant characteristics are not clearly reported in the paper, and so it is not possible to look at the diversity of the sample.
