A recent study, from researchers in Australia, examined the immune systems of individuals with ME/CFS and long COVID, focusing on immune exhaustion – a state in which the immune system becomes less effective over time. Immune exhaustion is an area that has been garnering increasing attention in ME/CFS research.
Methods
The researchers analysed changes in the activity of specific genes involved in immune responses. Genes, which are segments of DNA, provide instructions for producing proteins that perform essential body functions. Alterations in gene activity can profoundly impact health.
The study included 18 healthy controls, 14 individuals with ME/CFS, and 15 with long COVID. Whilst participants were matched for age and sex, there were significant differences in body mass index (BMI) between cohorts.
Findings
ME/CFS
In the ME/CFS cohort, five genes were more active (upregulated), and nine genes were less active (downregulated) compared to healthy controls. The changes indicated immune suppression, with reduced activity in pathways that combat infections and lower antibody production. The researchers highlighted that interferon signalling – key to the effectiveness of immune cells, T-cells and natural killer (NK) cells – was downregulated, suggesting immune exhaustion. However, the researchers highlighted previous studies that reported upregulated interferon signalling in ME/CFS, “contradicting the role of autoimmunity in the pathogenesis of ME/CFS.”
Long COVID
In the long COVID cohort, 15 genes were upregulated, and 14 were downregulated, and pointed to ongoing immune activation and inflammation. Types of T-cells, known as regulatory T cells (Tregs), which help control inflammation, were significantly reduced in long COVID compared to ME/CFS. This reduction could explain prolonged inflammation in long COVID. In ME/CFS, the role of Tregs is unclear – some prior studies suggest an increase in Tregs to counteract immune overactivity, whilst others showed a reduction in Tregs.
Overlapping Features
There were similarities between the ME/CFS and long COVID cohort, with “seven differentially expressed genes overlapped between patient cohorts, suggesting the involvement of similar molecular pathways involved in immune dysfunction.” Additionally, genes related to antibody production were downregulated in both conditions, indicating a weakened ability to fight infections.
Conclusion
The study highlights immune system dysfunction in both ME/CFS and long COVID. However, it is difficult to draw conclusions from the study about immune exhaustion as the researchers themselves point to other studies that show contradictory findings. The small sample size also limits the strength of the conclusions, emphasising the need more extensive research to confirm these results and explore their implications.
