Comparison of serum neurodegenerative biomarkers among hospitalized COVID‐19 patients versus non‐COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia

Frontera, Jennifer A.; Boutajangout, Allal; Masurkar, Arjun V.; Betensky, Rebecca A.; Ge, Yulin; Vedvyas, Alok; Debure, Ludovic; Moreira, André; Lewis, Ariane; Huang, Joshua Zhexue; Thawani, Sujata; Balcer, Laura J.; Galetta, Steven; Wısnıewskı, Thomas

doi:10.1002/alz.12556

Cited by 101 publications

(92 citation statements)

References 61 publications

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“…Interestingly, they found increased levels of inflammatory and neurodegenerative proteins in the cargo of these nEVs, which, if persistent, may indicate synaptic disruption and neuronal damage reminiscent of AD, PD, and TBI [ 13 ]. Results from a very recent study seem to be in agreement with these findings as blood biomarkers of neuronal and glial degeneration were found to be elevated in hospitalized COVID-19 patients with new onset cognitive dysfunction (specifically, toxic-metabolic encephalopathy, TME) [ 269 ]. Specifically, they showed increased levels of total tau, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) in the blood of neuro-COVID patients, which together indicated a profound neurological insult comparable to non-COVID patients with AD [ 269 , 270 ].…”

Section: Covid-19 and Neurodegenerationsupporting

confidence: 54%

“…Results from a very recent study seem to be in agreement with these findings as blood biomarkers of neuronal and glial degeneration were found to be elevated in hospitalized COVID-19 patients with new onset cognitive dysfunction (specifically, toxic-metabolic encephalopathy, TME) [ 269 ]. Specifically, they showed increased levels of total tau, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) in the blood of neuro-COVID patients, which together indicated a profound neurological insult comparable to non-COVID patients with AD [ 269 , 270 ]. It is of great significance to note that these neurodegenerative biomarkers are also elevated after BBB disruption and were found to be associated with a higher risk of in-hospital death and reduced rates of discharge from hospital [ 269 ].…”

Section: Covid-19 and Neurodegenerationsupporting

confidence: 54%

“…Specifically, they showed increased levels of total tau, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) in the blood of neuro-COVID patients, which together indicated a profound neurological insult comparable to non-COVID patients with AD [ 269 , 270 ]. It is of great significance to note that these neurodegenerative biomarkers are also elevated after BBB disruption and were found to be associated with a higher risk of in-hospital death and reduced rates of discharge from hospital [ 269 ]. The discovery of such comparatively fewer invasive blood biomarkers for cognitive impairment could help in monitoring neuronal and other brain cell health in real time, and to determine treatment responses in neuro-COVID.…”

Section: Covid-19 and Neurodegenerationmentioning

confidence: 99%

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A Peek into Pandora’s Box: COVID-19 and Neurodegeneration

Chandra¹,

Johri²

2022

Brain Sciences

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Ever since it was first reported in Wuhan, China, the coronavirus-induced disease of 2019 (COVID-19) has become an enigma of sorts with ever expanding reports of direct and indirect effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on almost all the vital organ systems. Along with inciting acute pulmonary complications, the virus attacks the cardiac, renal, hepatic, and gastrointestinal systems as well as the central nervous system (CNS). The person-to-person variability in susceptibility of individuals to disease severity still remains a puzzle, although the comorbidities and the age/gender of a person are believed to play a key role. SARS-CoV-2 needs angiotensin-converting enzyme 2 (ACE2) receptor for its infectivity, and the association between SARS-CoV-2 and ACE2 leads to a decline in ACE2 activity and its neuroprotective effects. Acute respiratory distress may also induce hypoxia, leading to increased oxidative stress and neurodegeneration. Infection of the neurons along with peripheral leukocytes’ activation results in proinflammatory cytokine release, rendering the brain more susceptible to neurodegenerative changes. Due to the advancement in molecular biology techniques and vaccine development programs, the world now has hope to relatively quickly study and combat the deadly virus. On the other side, however, the virus seems to be still evolving with new variants being discovered periodically. In keeping up with the pace of this virus, there has been an avalanche of studies. This review provides an update on the recent progress in adjudicating the CNS-related mechanisms of SARS-CoV-2 infection and its potential to incite or accelerate neurodegeneration in surviving patients. Current as well as emerging therapeutic opportunities and biomarker development are highlighted.

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Section: Covid-19 and Neurodegenerationsupporting

confidence: 54%

Section: Covid-19 and Neurodegenerationsupporting

confidence: 54%

Section: Covid-19 and Neurodegenerationmentioning

confidence: 99%

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A Peek into Pandora’s Box: COVID-19 and Neurodegeneration

Chandra¹,

Johri²

2022

Brain Sciences

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“…While our results and the work by Weinhoffer et al focused on CALD, the use of NfL has been previously demonstrated in a wide variety of conditions, including amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and most recently in COVID-19 infection [ 18 , 25 , 26 ]. In ALS, while it is not entirely clear that NfL can predict disease onset, there is evidence that high levels of Nfl predict a more rapid and aggressive course of disease [ 19 ].…”

Section: Discussionmentioning

confidence: 62%

Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy

Wang

Davison

Kramer

et al. 2022

Cells

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Cerebral adrenoleukodystrophy (CALD) is a devastating, demyelinating neuroinflammatory manifestation found in up to 40% of young males with an inherited mutation in ABCD1, the causative gene in adrenoleukodystrophy. The search for biomarkers which correlate to CALD disease burden and respond to intervention has long been sought after. We used the Olink Proximity Extension Assay (Uppsala, Sweden) to explore the cerebral spinal fluid (CSF) of young males with CALD followed by correlative analysis with plasma. Using the Target 96 Neuro Exploratory panel, we found that, of the five proteins significantly increased in CSF, only neurofilament light chain (NfL) showed a significant correlation between CSF and plasma levels. Young males with CALD had a 11.3-fold increase in plasma NfL compared with controls. Importantly, 9 of 11 young males with CALD who underwent HCT showed a mean decrease in plasma NfL of 50% at 1 year after HCT compared with pre-HCT levels. In conclusion, plasma NfL could be a great value in determining outcomes in CALD and should be scrutinized in future studies in patients prior to CALD development and after therapeutic intervention.

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“…Improvements in t-MoCA scores over time should generate a degree of optimism regarding recovery from long-COVID, particularly since "brain fog", confusion and dysexecutive function appear to be common protracted post-acute sequelae [29][30][31] . While the pathogenesis of post-acute cognitive dysfunction is likely multifactorial, possibilities include post-hypoxic brain injury, blood brain barrier disruption with ongoing inflammation, autoimmune mechanisms or even neurodegenerative disease 32 . Indeed, significant decay in premorbid to post-COVID MoCA scores has been documented in over 20% of patients with only mild symptomatic COVID.…”

Section: Discussionmentioning

confidence: 99%

Trajectories of Neurological Recovery 12 Months after Hospitalization for COVID-19: A Prospective Longitudinal Study

Frontera

Yang

medircherla

et al. 2022

Preprint

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Background/Objectives: Little is known about trajectories of recovery 12-months after hospitalization for severe COVID. Methods: We conducted a prospective, longitudinal cohort study of patients with and without neurological complications during index hospitalization for COVID-19 from March 10, 2020-May 20, 2020. Phone follow-up batteries were performed at 6- and 12-months post-COVID symptom onset. The primary 12-month outcome was the modified Rankin Scale (mRS) comparing patients with or without neurological complications using multivariable ordinal analysis. Secondary outcomes included: activities of daily living (Barthel Index), telephone Montreal Cognitive Assessment (t-MoCA) and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. Changes in outcome scores from 6 to 12-months were compared using non-parametric paired-samples sign test. Results: Twelve-month follow-up was completed in N=242 patients (median age 65, 64% male, 34% intubated during hospitalization) and N=174 completed both 6- and 12-month follow-up. At 12-months 197/227 (87%) had ≥1 abnormal metric: mRS>0 (75%), Barthel<100 (64%), t-MoCA≤18 (50%), high anxiety (7%), depression (4%), fatigue (9%) and poor sleep (10%). 12-month mRS scores did not differ significantly among those with (N=113) or without (N=129) neurological complications during hospitalization after adjusting for age, sex, race, pre-COVID mRS and intubation status (adjusted OR 1.4, 95% CI0.8-2.5), though those with neurological complications had higher fatigue scores (T-score 47 vs 44, P=0.037). Significant improvements in outcome trajectories from 6- to 12-months were observed in t-MoCA scores (56% improved, median difference 1 point, P=0.002), and Neuro-QoL anxiety scores (45% improved, P=0.003). Non-significant improvements occurred in fatigue, sleep and depression scores in 48%, 48% and 38% of patients, respectively. Barthel and mRS scores remained unchanged between 6 and 12-months in >50% of patients. Discussion: At 12-months post-hospitalization for severe COVID, 87% of patients had ongoing abnormalities in functional, cognitive or Neuro-QoL metrics and abnormal cognition persisted in 50% of patients without a prior history of dementia/cognitive abnormality. Only fatigue severity differed significantly between patients with or without neurological complications during index hospitalization. However, significant improvements in cognitive (t-MoCA) and anxiety (Neuro-QoL) scores occurred in 56% and 45% of patients, respectively, between 6- to 12-months. These results may not be generalizable to those with mild/moderate COVID.

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Comparison of serum neurodegenerative biomarkers among hospitalized COVID‐19 patients versus non‐COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia

Cited by 101 publications

References 61 publications

A Peek into Pandora’s Box: COVID-19 and Neurodegeneration

A Peek into Pandora’s Box: COVID-19 and Neurodegeneration

Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy

Trajectories of Neurological Recovery 12 Months after Hospitalization for COVID-19: A Prospective Longitudinal Study

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