High Levels of NfL, GFAP, TAU, and UCH-L1 as Potential Predictor Biomarkers of Severity and Lethality in Acute COVID-19

Salvio, Andreza Lemos; Fernandes, Renan Amphilophio; Ferreira, Helena França Alcaraz; Duarte, Larissa Araujo; Gutman, Elisa Gouvea; Raposo-Vedovi, Jessica Vasques; Filho, Carlos Henrique Ferreira Ramos; da Costa Nunes Pimentel Coelho, Wagner Luis; Passos, Giselle Fazzioni; Andraus, Maria Emília Cosenza; da Costa Gonçalves, João Paulo; Cavalcanti, Marta Guimarães; Amaro, Marisa Pimentel; Kader, Rafael; de Andrade Medronho, Roberto; Figueiredo, Cláudia Pinto; Amado-Leon, Luciane Almeida; Alves-Leon, Soniza Vieira

doi:10.1007/s12035-023-03803-z

Cited by 4 publications

(2 citation statements)

References 55 publications

(79 reference statements)

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“…In contrast, the levels of serum GFAP levels did not exhibit a significant difference between the two groups (Table 2). These may suggest that the SARS‐CoV‐2 upon CNS invasion can cause more direct and pronounced damage to neurons or nerve fiber 17,18,35 …”

Section: Resultsmentioning

confidence: 99%

Current clinical findings of acute neurological syndromes after SARS‐CoV‐2 infection

Wang,

Ren

et al. 2024

MedComm

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Neuro‐COVID, a condition marked by persistent symptoms post‐COVID‐19 infection, notably affects various organs, with a particular focus on the central nervous system (CNS). Despite scant evidence of SARS‐CoV‐2 invasion in the CNS, the increasing incidence of Neuro‐COVID cases indicates the onset of acute neurological symptoms early in infection. The Omicron variant, distinguished by heightened neurotropism, penetrates the CNS via the olfactory bulb. This direct invasion induces inflammation and neuronal damage, emphasizing the need for vigilance regarding potential neurological complications. Our multicenter study represents a groundbreaking revelation, documenting the definite presence of SARS‐CoV‐2 in the cerebrospinal fluid (CSF) of a significant proportion of Neuro‐COVID patients. Furthermore, notable differences emerged between RNA‐CSF‐positive and negative patients, encompassing aspects such as blood–brain barrier integrity, extent of neuronal damage, and the activation status of inflammation. Despite inherent limitations, this research provides pivotal insights into the intricate interplay between SARS‐CoV‐2 and the CNS, underscoring the necessity for ongoing research to fully comprehend the virus's enduring effects on the CNS. The findings underscore the urgency of continuous investigation Neuro‐COVID to unravel the complexities of this relationship, and pivotal in addressing the long‐term consequences of COVID‐19 on neurological health.

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Section: Resultsmentioning

confidence: 99%

Current clinical findings of acute neurological syndromes after SARS‐CoV‐2 infection

Wang,

Ren

et al. 2024

MedComm

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“…NFL and tTau have been linked to critical illness in ICUs independent of an underlying neurological cause and showed correlation with both disease severity and clinical outcomes, for example, in the context of severe SARS-CoV-2 infections ( 43 , 44 ). None of the delirium patients in our study were critically ill and were admitted to an ICU; however, it could be considered a potentially limiting factor for the clinical utility of these biomarkers since delirium is particularly relevant in ICU settings ( 4 ).…”

Section: Discussionmentioning

confidence: 99%

Serum NFL and tau, but not serum UCHL-1 and GFAP or CSF SNAP-25, NPTX2, or sTREM2, correlate with delirium in a 3-year retrospective analysis

Piel,

Bargemann,

Leypoldt

et al. 2024

Front. Neurol.

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Delirium represents a common terminal pathway of heterogeneous neurological conditions characterized by disturbances in consciousness and attention. Contemporary theories highlight the acute impairment of synaptic function and network connectivity, driven by neuroinflammation, oxidative stress, and neurotransmitter imbalances. However, established biomarkers are still missing. Innovative diagnostic techniques, such as single-molecule array analysis, enable the detection of biomarkers in blood at picomolar concentrations. This approach paves the way for deeper insights into delirium and potentially therapeutic targets for tailored medical treatments. In a retrospective 3-year study, we investigated seven biomarkers indicative of neuroaxonal damage [neurofilament light chain (NFL), ubiquitin carboxyl-terminal hydrolase (UCHL-1), and tau protein], microglial activation [glial fibrillary acidic protein (GFAP) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2)], and synaptic dysfunction [synaptosomal-associated protein 25 (SNAP-25) and neuronal pentraxin 2 (NPTX2)]. The analysis of 71 patients with delirium, Alzheimer’s disease (AD), and non-AD controls revealed that serum NFL levels are higher in delirium cases compared to both AD and non-AD. This suggests that elevated NFL levels in delirium are not exclusively the result of dementia-related damage. Serum tau levels were also elevated in delirium cases compared to controls. Conversely, cerebrospinal fluid (CSF) SNAP-25 showed higher levels in AD patients compared to controls only. These findings add to the increasing body of evidence suggesting that serum NFL could be a valuable biomarker of neuroaxonal damage in delirium research. Although SNAP-25 and NPTX2 did not exhibit significant differences in delirium, the exploration of synaptic biomarkers remains promising for enhancing our understanding of this condition.

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Drug Repurposing for COVID-19 by Constructing a Comorbidity Network with Central Nervous System Disorders

Qian,

Yang,

Wang

et al. 2024

IJMS

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In the post-COVID-19 era, treatment options for potential SARS-CoV-2 outbreaks remain limited. An increased incidence of central nervous system (CNS) disorders has been observed in long-term COVID-19 patients. Understanding the shared molecular mechanisms between these conditions may provide new insights for developing effective therapies. This study developed an integrative drug-repurposing framework for COVID-19, leveraging comorbidity data with CNS disorders, network-based modular analysis, and dynamic perturbation analysis to identify potential drug targets and candidates against SARS-CoV-2. We constructed a comorbidity network based on the literature and data collection, including COVID-19-related proteins and genes associated with Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and autism spectrum disorder. Functional module detection and annotation identified a module primarily involved in protein synthesis as a key target module, utilizing connectivity map drug perturbation data. Through the construction of a weighted drug–target network and dynamic network-based drug-repurposing analysis, ubiquitin–carboxy-terminal hydrolase L1 emerged as a potential drug target. Molecular dynamics simulations suggested pregnenolone and BRD-K87426499 as two drug candidates for COVID-19. This study introduces a dynamic-perturbation-network-based drug-repurposing approach to identify COVID-19 drug targets and candidates by incorporating the comorbidity conditions of CNS disorders.

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High Levels of NfL, GFAP, TAU, and UCH-L1 as Potential Predictor Biomarkers of Severity and Lethality in Acute COVID-19

Cited by 4 publications

References 55 publications

Current clinical findings of acute neurological syndromes after SARS‐CoV‐2 infection

Current clinical findings of acute neurological syndromes after SARS‐CoV‐2 infection

Serum NFL and tau, but not serum UCHL-1 and GFAP or CSF SNAP-25, NPTX2, or sTREM2, correlate with delirium in a 3-year retrospective analysis

Drug Repurposing for COVID-19 by Constructing a Comorbidity Network with Central Nervous System Disorders

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