Serum Spike Protein Persistence Post COVID Is Not Associated with ME/CFS.
Fehrer, Annick, Sotzny, Franziska, Kim, Laura et al. · Journal of clinical medicine · 2025 · DOI
Quick Summary
Researchers tested whether a piece of the COVID-19 virus (spike protein) lingering in the blood after infection could explain ME/CFS symptoms. They found spike protein in some patients' blood months after COVID, but it was present in similar amounts in people who recovered well and those with ME/CFS. This suggests that leftover spike protein is probably not the main cause of ME/CFS.
Why It Matters
Understanding whether persistent viral proteins drive ME/CFS is crucial for identifying treatment targets and explaining disease mechanisms in post-COVID patients. This study provides evidence that spike protein alone does not explain ME/CFS development, potentially redirecting research toward other mechanisms such as immune dysregulation, viral persistence in other tissues, or autonomic dysfunction.
Observed Findings
Spike protein was detected in 14% of ME/CFS patients, 11% of recovered healthy controls, and 2% of post-COVID patients, with no significant difference between groups.
Spike protein presence did not correlate with infection or vaccination timing.
In ME/CFS patients, the presence or concentration of spike protein showed no association with symptom severity or functional disability.
When immunoglobulin depletion was performed on 22 patients, spike protein levels were reduced or undetectable in 5 cases, indicating binding to immune molecules.
Spike protein was not detected in any pre-pandemic control samples, confirming post-COVID origin.
Inferred Conclusions
Serum spike protein persistence is not a primary mechanism driving ME/CFS development or symptom severity.
Persistent spike protein, when present, appears to be bound to immunoglobulins rather than freely circulating.
ME/CFS pathophysiology likely involves mechanisms other than circulating spike protein accumulation.
Persistent spike protein occurs similarly in recovered and post-COVID patients, suggesting it is not a distinguishing feature of ME/CFS.
Remaining Questions
Why does spike protein persist in some individuals but not others, and what determines its clearance or sequestration?
What This Study Does Not Prove
This study does not prove that spike protein plays no role in any post-COVID symptoms—only that it is not associated with ME/CFS specifically. It also does not establish causation and cannot rule out spike protein involvement in other tissues or other post-COVID conditions. The small number of spike protein-positive samples limits statistical power to detect associations if they exist.