Chronic viral infections in myalgic encephalomyelitis/ chronic fatigue syndrome  (ME/CFS), by Santa Rasa, Zaiga Nora-Krukle, Nina Henning, Eva Eliassen, Evelina Shikova, Thomas Harrer, Carmen Scheibenbogen, Modra Murovska, Bhupesh K Prusty and the European Network on ME/CFS (EUROMENE) in Journal of Translation Medicine 2018, #16 p 268, August 2, 2018 [Published: 1 October 2018]

Review abstract:

Background and main text:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals.

Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies.

Conclusions:
This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.

Review Conclusions:

Currently available data on the role of chronic viral infection with ME/CFS is still controversial, showing potential viral involvement for at least a subgroup of ME/CFS patients. Therefore, it is necessary to assess the presence and markers of viral activity at the initial stage of the disease to evaluate possible etiological factors and conduct longitudinal studies in order to assess active viral infection and symptom severity variations over time. Moreover, results should be compared not only between ME/CFS patients and controls, but also with other co-morbidities to assess specificity of suggested biomarkers.

Considering ME/CFS heterogeneity, the use of clinical characteristics and biomarkers to enable definition of the disease subtypes is crucial. In addition, longitudinal and standardized studies determining ME/CFS course and therapy effectiveness with follow-up measurements in dynamics should be accomplished. This will allow prognosis of the disease development and promote development of a specific definition for diagnostics and a treatment plan.

Future strategies for development of infection biomarkers in ME/CFS

1. Use of quantitative assays rather than qualitative assays to assess the extent of the viral load instead of simple detection of presence or absence. This may facilitate monitoring of a response to treatment; however, diurnal variations and individual response on treatment should be taken into account. Further comprehensive serological testing may help to identify a signature of active infection.
2. Use of additional biological samples together with blood and serum will be useful in determining the localization and distribution of biomarkers, as well as pathogenicity. Using hair follicles, virus integration can be detected. Similarly throat swab and stool samples can be used for detection of enteroviruses.
3. Functional studies to compliment clinical biomarker studies in order to clarify functions and interactions of genes, transcripts, proteins, and immune cells and molecules in cases of ME/CFS. This will facilitate understanding of the disease aetiology as well as development and maintenance pathways, and thereby, potential prevention and treatment strategies. However, this strategy requires definition of ME/CFS subgroups.
4. Use of high throughput methods to gain broader insight into potential biomarkers for infections by obtaining and analysing large-scale data, which will raise the quality and significance of the research.
5. Confirmation of results by validation studies and multi-centre cohort studies to obtain generalizability of the study and promote implementation of credible biomarkers usable worldwide.