Ask your competent? doctor if this explains and could prevent post stroke fatigue.
Study finds shared biological pathways in long COVID and other fatigue-linked disorders
A computational study using 3-dimensional (3D) genomic analysis has identified biological convergence across myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), long COVID, post-traumatic stress disorder (PTSD), rheumatoid arthritis (RA), and multiple sclerosis (MS), suggesting that profoundly different triggers may ultimately disrupt the same fundamental regulatory systems to produce similar, disabling exhaustion.
The study, published in the Journal of Translational Medicine, was led by researchers at the University of East Anglia (UEA), Norwich, UK. Despite being initiated by markedly different events -- ranging from viral infection and psychological trauma to autoimmune processes -- all 5 conditions share the defining clinical feature of severe, persistent fatigue.
Professor Dmitry Pshezhetskiy, UEA, Norwich, said: "Until now, illnesses including long COVID, PTSD, ME/CFS, MS and RA were viewed as seemingly unrelated and triggered by completely different events ... But one thing that links them all is that patients frequently report remarkably similar symptoms -- overwhelming fatigue, brain fog, poor concentration, disturbed sleep, autonomic dysfunction and a dramatic reduction in everyday functioning."
Rather than collecting new patient samples, the team integrated published genome-wide association study (GWAS) data for long COVID, PTSD, RA, and MS with 3D genomic data from an existing ME/CFS patient study, using the EpiSwitch Orion platform. This tool examines how DNA folds and interacts within living cells, revealing regulatory interactions invisible to conventional linear genomic analysis. Disease-specific genetic variants were mapped to chromosomal anchor points, and protein-protein interaction networks were constructed and merged across all 5 conditions.
The analysis revealed minimal gene-level overlap between the 5 conditions. Pshezhetskiy said: "We expected to find at least some overlap in genes across the conditions. But we actually found the opposite. At an individual gene level, there was surprisingly little direct overlap between long COVID, ME/CFS, PTSD, MS and RA."
"But when we analysed how those genes interact in complex biological networks, a completely different picture emerged. Suddenly, the diseases appeared deeply connected," Pshezhetskiy elaborated.
At the network level, the 5 conditions converged on shared biological pathways including immune and inflammatory signalling, mitochondrial energy production, metabolic regulation, stress-response mechanisms, and neuroendocrine signalling.
To explain why infections and trauma can produce identical symptoms, Pshezhetskiy said: "We now think the answer may lie in shared regulatory networks embedded within the body's immune and metabolic systems."
"A COVID-19 infection may trigger prolonged immune activation. Traumatic stress may disrupt stress-hormone pathways and inflammatory responses,” Pshezhetskiy added. “But both disturbances appear capable of converging on common biological circuits controlling energy production, immune regulation and cellular resilience. When those systems become persistently dysregulated, the result may be the profound and disabling fatigue seen across multiple disorders."
Regarding diagnostic implications, Pshezhetskiy said, "ME/CFS and long COVID-19 are currently diagnosed largely through symptoms, with no universally accepted laboratory test available. That has left many patients facing years of uncertainty."
Pshezhetskiy said he hoped the findings "could pave the way for objective blood tests capable of identifying underlying biological signatures rather than relying solely on patient-reported symptoms."
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