EBioMedicineJan 6, 2026

Higher levels of a brain protein linked to neurological symptoms after COVID-19 in essential workers

Updated Jun 27, 2026

Abstract

Essence

Neurological long COVID with central symptoms was linked to post-infection increases in plasma pTau-181 among essential workers.

Evidence

This prospective matched cohort study compared pre- and post-COVID plasma neurological biomarkers in 227 essential workers with N-PASC and 227 controls.

Caveat

The biomarker changes were associated with symptom patterns and amyloid markers, but they do not prove that COVID-19 caused Alzheimer-like disease processes.

Simplified

BACKGROUND: The COVID-19 pandemic led to a spectrum of post-acute sequelae including several neurological complications including cognitive dysfunction labelled Neurological PASC (N-PASC). We hypothesised that N-PASC was associated with changes in neurological biomarkers after COVID-19.

METHODS: N-PASC was established when individuals reported accepted neurological symptoms persisting for ≥3 months arising alongside validated COVID-19. Plasma samples were retrieved from before and after COVID-19 onset among all (n = 227) essential workers who developed COVID-19 with N-PASC and demographically matched with data from 227 controls who either developed COVID-19 without N-PASC (n = 124) or did not develop COVID-19 before follow-up (n = 103). We used single molecular analysis measured pTau-181, GFAP, NfL, Aβ40/42, and total Aβ burden (IAB). Risk factors for N-PASC were examined prior to COVID-19 infection. Multivariable adjusted generalised linear longitudinal modelling with random intercepts was used to examine changes in biomarkers after COVID-19 onset.

FINDINGS: N-PASC was only associated with higher IAB before COVID-19 onset (area under the receiver-operating curve = 0.77). Longitudinal analyses revealed plasma pTau-181 levels increased by 59.3% (95% C.I. = [45.2, 73.4] P = 0.006) following COVID-19 onset in participants who developed N-PASC that were worst among participants reporting central nervous symptoms persisting ≥1.5 years. Post-COVID-19 decreased GFAP and NfL were associated with peripheral symptoms of N-PASC, but not with increased pTau-181. Having ≥20% increases in pTau-181 were associated with increased Aβ40/42 levels at follow-up, and with central neurological symptoms including lingering brain fog and loss of taste/smell.

INTERPRETATION: N-PASC with symptoms consistent with central damage were associated with increased pTau-181 levels. Increases in pTau-181 were associated with increased risk of changes to amyloid biomarkers consistent with Alzheimer's disease in participants with N-PASC and could therefore inform N-PASC prognostication.

FUNDING: This study was supported in part by funding from the Centers for Disease Control and Prevention (CDC/NIOSH CDC-75D30122c15522) and the National Institutes of Health (NIH/NIA AG049953).