Mapping the complexity of ME/CFS: Evidence for abnormal energy metabolism, altered immune profile, and vascular dysfunction

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder with undefined mechanisms, no diagnostic tools and treatments. To investigate concurrent system dysfunctions, we recruited age- and sex-matched ME/CFS patients and healthy controls for a multimodal analysis of energy metabolism, immune profiles, and plasma proteomics.

Immune cells from ME/CFS patients show elevated adenosine monophosphate (AMP) and adenosine diphosphate (ADP) with a reduced ATP/ADP ratio, indicating decreased ATP generation and cellular energy stress. Immune profiling reveals skewing toward less mature effector subsets of CD4+, CD8+, and γδ T cells, with reduced CD1c+CD141 conventional DC type 2 and CD56lowCD16+ terminal natural killer cells.

Elevated levels of plasma proteins associated with thrombus formation and vascular reactivity may contribute to the endothelial dysfunction observed in ME/CFS patients. Classification and regression tree modeling identifies variables with strong predictive potential for ME/CFS. Together, this study provides insights into the somatic symptoms and underlying biology of ME/CFS.

Source: Heng B, Gunasegaran B, Krishnamurthy S, Bustamante S, Pires AS, Chow S, Ahn SB, Paul-Heng M, Maciver Y, Smith K, Tran DP, Howley PP, Bilgin AA, Sharland A, Schloeffel R, Guillemin GJ. Mapping the complexity of ME/CFS: Evidence for abnormal energy metabolism, altered immune profile, and vascular dysfunction. Cell Rep Med. 2025 Dec 16;6(12):102514. doi: 10.1016/j.xcrm.2025.102514. PMID: 41406947. https://www.sciencedirect.com/science/article/pii/S2666379125005877 (Full text)

Circulating microaggregates as biomarkers for the Post‐COVID syndrome

Abstract:

CoVID-19 can develop into Post-COVID syndrome of potentially high morbidity, with procoagulation and reactivation of dormant viral infections being hypothesized pathophysiological mechanisms. We report on a patient suffering from fatigue, post exertional malaise, pain and neurological symptoms as a consequence of the second CoVID infection. Using live confocal microscopy on native whole blood samples we detected microaggregates of thrombocytes, leukocytes and plasma proteins in peripheral blood.

In addition, there was specific cellular immunological reactivity to EBV. Upon anticoagulatory and virustatic pharmacological therapy we observed dissolution of microaggregates and significant stable clinical remission. We suggest to consider circulating microaggregates as a morphological indicator of chronic post-COVID syndrome.

Source: M. Hermann , C. Lisch, R. Gerth, G. Wick, D. Fries, N. Wick. Circulating microaggregates as biomarkers for the Post‐COVID syndrome. IDCases, Volume 36, 2024, e02000. https://www.sciencedirect.com/science/article/pii/S2214250924000763 (Full text)