A new study published in eBioMedicine reports that individuals who develop persistent neurological symptoms following SARS-CoV-2 infection show significantly increased blood levels of a protein strongly associated with neurodegenerative disease, raising concerns about the long-term impact of COVID-19 on brain health.
The study analyzed 227 individuals who experienced post-acute neurocognitive symptoms after COVID-19, including headache, vertigo, balance disturbance, anosmia/dysgeusia, and persistent cognitive impairment commonly referred to as “brain fog.” Researchers found that these patients had markedly elevated plasma levels of tau protein after infection compared with samples obtained years before they contracted COVID-19.
Tau is a microtubule-associated protein expressed primarily in neurons, where it stabilizes axonal structure. Pathological forms of tau, particularly phosphorylated tau, are a hallmark of Alzheimer’s disease and other tauopathies. In this study, investigators focused on phosphorylated tau-181 (pTau-181), a biomarker widely used in dementia research. Participants with neurological post-acute sequelae of COVID-19 (N-PASC) demonstrated a 59% increase in pTau-181 levels post-infection compared with their own pre-COVID baselines. By contrast, a matched control group of 227 individuals from the same cohort, either uninfected or who recovered from COVID-19 without long-term symptoms, did not show significant changes in plasma tau levels.
The research was conducted within the Stony Brook World Trade Center (WTC) Health and Wellness Program, which follows responders to the September 11, 2001 attacks. A major strength of the study is the availability of pre-pandemic blood samples, allowing for direct within-person comparisons before and after SARS-CoV-2 infection. Plasma tau was measured a mean of 2.2 years after COVID-19, with a range of six months to four years, reflecting what the authors describe as a “true long-term” post-acute effect. Participants whose neurological symptoms persisted for more than 1.5 years exhibited even greater increases in pTau-181, suggesting a potential relationship between symptom duration and neurodegenerative biomarker burden.
Despite the striking association, the authors caution that elevated plasma tau does not necessarily indicate increased tau deposition in the brain. Additional studies incorporating neuroimaging and longitudinal cognitive assessments will be required to determine whether these biomarker changes translate into measurable neurodegeneration or cognitive decline.
The researchers also acknowledge that WTC responders represent a unique population with specific environmental and occupational exposures, which may limit generalizability to the broader Long COVID population.
The findings add to growing evidence that viral infections may contribute to long-term neurobiological changes. This is one of the first studies to suggest that SARS-CoV-2 infection may drive abnormal tau production over time, with important implications for understanding the mechanisms of neurodegenerative disease and for the development of preventive strategies, including vaccines and early therapeutic interventions.
If confirmed in larger and more diverse populations, these data suggest that the neurological consequences of COVID-19 may extend well beyond the acute phase of infection and could contribute to future burdens of cognitive impairment and dementia-like syndromes.
Reference
- Yang X, Fontana A, Clouston SAP, Luft BJ. Increased phosphorylated tau (pTau-181) is associated with neurological post-acute sequelae of coronavirus disease in essential workers: a prospective cohort study before and after COVID-19 onset. eBioMedicine [Internet]. 2026 Jan 1 [cited 2026 Jan 24];123. Available from: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00556-0/fulltext