NEW evidence from a prospective cohort study suggests that elevated plasma phosphorylated tau (pTau-181) may be a critical biomarker in patients experiencing neurological post-acute sequelae of COVID-19 (N-PASC), particularly among essential workers.
N-PASC and pTau-181: Key Biomarker Insights
Researchers followed 227 essential workers who developed COVID-19 and subsequently experienced N-PASC, comparing them with 227 demographically matched controls who either recovered without neurological symptoms or did not contract the virus. Using single molecular analysis, the study measured changes in neurological biomarkers including pTau-181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and amyloid beta (Aβ40/42 and total Aβ burden, IAB).
Significant Increases in pTau-181 Post-COVID
The findings revealed a striking 59.3% increase in plasma pTau-181 levels among participants with N-PASC following COVID-19 onset, with the greatest elevations in those reporting persistent central nervous system symptoms, commonly described as brain fog, cognitive difficulties, and loss of taste or smell, lasting 18 months or more. In contrast, GFAP and NfL reductions were linked to peripheral neurological symptoms, suggesting distinct biomarker profiles depending on symptom localisation.
Amyloid Changes and Prognostic Potential
Participants exhibiting at least a 20% increase in pTau-181 also showed higher Aβ40/42 levels at follow-up. This association with amyloid biomarkers aligns with patterns observed in Alzheimer’s disease, hinting at potential long-term neurodegenerative risks in a subset of N-PASC patients. Interestingly, elevated total Aβ burden prior to COVID-19 was identified as a potential predisposing factor for developing N-PASC, providing clinicians with a possible predictive marker for risk stratification.
Clinical Implications for Healthcare Practitioners
For clinicians managing post-COVID patients, pTau-181 measurement may offer a valuable tool for identifying individuals at heightened risk of prolonged neurological symptoms. While causality remains unconfirmed, monitoring longitudinal biomarker changes could inform follow-up strategies and help prioritise interventions for those with central neurological manifestations. These findings emphasise the need for multidisciplinary approaches in the management of N-PASC, integrating neurology, rehabilitation, and primary care.
Reference
Yang X et al. 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. 2026; DOI:10.1016/j.ebiom.2025.106106.
