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

Details

• Journal Article:
  EBioMedicine
• Personal Author:
  Yang, Xiaohua ; Fontana, Ashley E. ; Clouston, Sean A. P. ; Luft, Benjamin J.
• Description:
  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.
• Subjects:
  Cognition COVID-19 Occupational Health Post-Acute COVID-19 Syndrome Safety
• Keywords:
  Author Keywords: Phosphorylated Tau-181; Neurological Biomarkers; Post-acute Sequelae Of COVID-19; Coronavirus Disease Cohort Studies; COVID-19; Cognitive Function; Neurological Disorders; Biomarkers; Longitudinal Study; Long COVID;
• Source:
  EBioMedicine 2026 Jan; 123:106106
• ISSN:
  2352-3964
• Document Type:
  Text
• Funding:
  Contract
• Genre:
  Journal Article
• Place as Subject:
  New York ; New York City Region [OSHA]
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  12 pdf pages
• Volume:
  123
• NIOSHTIC Number:
  nn:20071492
• Contact Point Address:
  Sean A.P. Clouston, Program in Public Health, Renaissance School of Medicine, Stony Brook University, 101 Nichols Road, Building 4, Stony Brook, NY, 11794, USA
• Email:
  sean.clouston@stonybrookmedicine.edu
• Federal Fiscal Year:
  2026
• Performing Organization:
  The Research Foundation for the State University of New York
• Peer Reviewed:
  True
• Start Date:
  20220929
• End Date:
  20260928
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:892684b4dc2d77c3d37a65e927667553aa0c1e8241379d3e460441a833c581af67179a7db1706cb1574c46816766e43e54118d1f337e9257e1d60b69c264d5a8
• Download URL:
  https://stacks.cdc.gov/view/cdc/259090/cdc_259090_DS1.pdf
• File Type:
  [PDF - 3.21 MB ]