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).
