Nikhil Prasad Fact checked by:Thailand Medical News Team Nov 04, 2026 43 minutes ago
New research from Spain has uncovered an important disturbance in the immune system of people with Long COVID, highlighting abnormalities in the interleukin-1 (IL-1) inflammatory pathway even months after their initial coronavirus infection. However, scientists found no single blood biomarker capable of reliably distinguishing patients with persistent symptoms from those who recovered.
Researchers identify persistent IL-1 immune pathway abnormalities in Long COVID patients, alongside vascular changes
and altered Epstein-Barr virus antibody responses
The study involved researchers from IrsiCaixa, ISGlobal, University of Barcelona, Germans Trias i Pujol Research Institute, Germans Trias i Pujol Hospital, Fight Against Infections Foundation, Instituto de Salud Carlos III research networks, University of Vic-Central University of Catalonia, CaixaResearch Institute, Universidad San Sebastián, and Case Western Reserve University School of Medicine.
Blood Tests Reveal Persistent Immune Abnormalities
Researchers examined 312 unvaccinated participants, including 139 Long COVID patients, 99 recovered COVID-19 patients, and 74 uninfected controls. Blood samples were collected approximately eight months after infection.
The investigation assessed inflammatory proteins, vascular injury markers, coronavirus RNA, and antibody responses to SARS-CoV-2 and other viruses.
The strongest finding involved IL-1 receptor antagonist (IL-1RA), a protein that helps regulate inflammation by blocking IL-1 signaling.
IL-1RA concentrations were significantly higher in Long COVID patients than in recovered individuals, with a statistical significance of p<0.001.
Researchers also identified a reduced ratio between IL-1 beta and IL-1RA, suggesting an altered balance between inflammatory signaling and the body's mechanisms for controlling inflammation.
Importantly, this
Thailand Medical News report highlights that these abnormalities could reflect persistent immune dysregulation rather than simply elevated inflammation.
Blood Vessel Changes and Viral Persistence
Investigators also examined P-selectin, a protein associated with platelet activation and blood vessel inflammation.
P-selectin levels were elevated in Long COVID patients compared with uninfected controls, suggesting possible vascular disturbances. However, its association with persistent symptoms was not statistically significant after adjustment for multiple comparisons.
Coronavirus RNA was detected in 7.2% of Long COVID patients and 4.3% of recovered participants. This difference was not statistically significant, indicating that detectable viral genetic material in blood was not exclusive to Long COVID.
Epstein-Barr Virus Antibodies Show Another Clue
Researchers discovered altered antibody patterns associated with Epstein-Barr virus (EBV), a herpesvirus capable of remaining dormant inside the body.
Long COVID patients displayed stronger antibod
y signatures associated with EBV reactivation and weaker latency-associated profiles.
An integrated EBV reactivation-associated antibody index was significantly higher than in recovered participants (p=0.007).
These findings suggest possible interactions between persistent immune disturbances and latent viral activity, although antibody patterns alone cannot establish active viral reactivation.
No Reliable Diagnostic Signature Emerges
Machine-learning analysis showed that combining immune, vascular, and viral markers still failed to reliably identify Long COVID.
The combined model achieved an accuracy measure of 0.633, indicating limited diagnostic usefulness.
Researchers also identified three symptom groups, ranging from predominantly fatigue and breathlessness to severe multisystem illness involving a median of 17 symptoms.
Conclusions
The findings strengthen evidence that Long COVID involves overlapping immune and vascular abnormalities, potentially alongside altered viral responses. However, the observational study cannot establish causation, and larger studies are needed to develop reliable diagnostic tests and targeted treatments.
The study findings were published in the peer reviewed journal: Frontiers in Immunology.
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1957339/full
Read Also:
https://www.thailandmedical.news/articles/long-covid
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