Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients

DeKosky, Steven T.; Kochanek, Patrick M.; Valadka, Alex B.; Clark, Robert S. B.; Chou, Sherry Hsiang‐Yi; Au, Alicia K.; Horvat, Christopher M.; Jha, Ruchira M.; Mannix, Rebekah; Wisniewski, Stephen R.; Wintermark, Max; Rowell, Susan; Welch, Robert D.; Lewis, Lawrence M.; House, Stacey L.; Tanzi, Rudolph E.; Smith, Darci R.; Vittor, Amy Y.; Denslow, Nancy D.; Davis, Michael D.; Glushakova, Olena; Hayes, Ronald L.

doi:10.1089/neu.2020.7332

Cited by 73 publications

(96 citation statements)

References 338 publications

(299 reference statements)

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“…Further, Gigli et al suggested that some patients may have a specific genetic predisposition to postinfectious inflammatory syndromes and associated intrathecal cytokine responses after COVID-19 [ 98 ]. Of course, it is imperative to recognize that elevated CSF and serum biomarkers is not clearly indicative of neuroinvasion as this can result from other mechanisms such as hypoxic injury [ 267 , 268 ]. Additional research into treatment implications and the diagnostic and prognostic value of CSF biomarkers in patients with COVID-19 who have neurological symptoms is needed.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid in COVID-19: A systematic review of the literature

Lewis

Frontera

Placantonakis

et al. 2021

Journal of the Neurological Sciences

150

152

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We sought to review the literature on cerebrospinal fluid (CSF) testing in patients with COVID-19 for evidence of viral neuroinvasion by SARS-CoV-2. Methods: We performed a systematic review of Medline and Embase between December 1, 2019 and November 18, 2020 to identify case reports or series of patients who had COVID-19 diagnosed based on positive SARS-CoV-2 polymerase chain reaction (PCR) or serologic testing and had CSF testing due to a neurologic symptom. Results: We identified 242 relevant documents which included 430 patients with COVID-19 who had acute neurological symptoms prompting CSF testing. Of those, 321 (75%) patients had symptoms that localized to the central nervous system (CNS). Of 304 patients whose CSF was tested for SARS-CoV-2 PCR, there were 17 (6%) whose test was positive, all of whom had symptoms that localized to the central nervous system (CNS). The majority (13/17, 76%) of these patients were admitted to the hospital because of neurological symptoms. Of 58 patients whose CSF was tested for SARS-CoV-2 antibody, 7 (12%) had positive antibodies with evidence of intrathecal synthesis, all of whom had symptoms that localized to the CNS. Of 132 patients who had oligoclonal bands evaluated, 3 (2%) had evidence of intrathecal antibody synthesis. Of 77 patients tested for autoimmune antibodies in the CSF, 4 (5%) had positive findings. Conclusion: Detection of SARS-CoV-2 in CSF via PCR or evaluation for intrathecal antibody synthesis appears to be rare. Most neurological complications associated with SARS-CoV-2 are unlikely to be related to direct viral neuroinvasion.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid in COVID-19: A systematic review of the literature

Lewis

Frontera

Placantonakis

et al. 2021

Journal of the Neurological Sciences

150

152

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“…GFAP and UCH-L1 blood serum markers may also be useful for detecting the long lasting neurological damage found in some COVID-19 patients. 8 The findings of this study demonstrate the utility of using the two serum biomarkers GFAP and UCH-L1 for classification of diverse TBIs. This study is limited to small sample sizes for each type of pathology and necessitates investigation of larger sample sizes to overcome potential sampling bias.…”

Section: Discussionmentioning

confidence: 59%

“…The highest levels of GFAP were found in individuals diagnosed with skull fractures combined with ICH. 4 Additional research suggests that serum GFAP concentrations are an ideal biomarker to differentiate between various nontraumatic brain injuries such as ICH and acute ischemic stroke (AIS) with higher GFAP elevations presenting in cases where damage was more extensive 3,[5][6][7][8] Research on serum biomarkers has also shown that UCH-L1, an enzyme responsible for degradation in nerve cells, may also offer useful information in the classification and severity of brain injuries and has been associated with poor outcomes in individuals with both traumatic and nontraumatic brain injuries. 9 UCH-L1 is hypothesized to play a role in axon and neuronal repair by removing abnormal proteins that are present after injury.…”

Section: Introductionmentioning

confidence: 99%

Machine Learning with Objective Serum Markers and Algorithmic Deep Learning Computed Tomography Scan Analysis for Classification of Brain Injury

Rafter

Schaaf

et al. 2021

Preprint

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Brain injury is pathophysiologically diverse, with many cases presenting with mixed pathologies. Utilizing serum biomarkers to investigate the pathophysiology of injury would help to aid in understanding prognosis and targeting therapeutics. One goal of the study is to develop a traumatic brain injury classification scheme based on two serum biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal L1 (UCH-L1). GFAP and UCH-L1 serum marker analysis was performed on patients with isolated traumatic brain injury or healthy, uninjured controls within 32 hours of hospital admission. Machine learning was utilized for classification of brain injury and to develop a novel algorithm capable of classifying the type of brain injury based on GFAP and UCH-L1 concentrations. Each patients brain injury was classified using standard clinical and radiographic assessments and stratified into one of four trauma groups: trauma, spontaneous hemorrhage, oxygen deprivation, or a high-velocity trauma with negative radiographic finding. Analysis of prospectively collected serum for GFAP and UCH-L1 was performed on 61 patients and 39 controls. The subjects with trauma, spontaneous hemorrhages and oxygen deprivation could be distinguished from controls with AUC = 1.00. Combination of GFAP and UCH-L1 concentrations distinguished the high-velocity injuries that were negative for radiographic indicators (CT-negative) from controls with AUC of 0.93. Serum biomarker profiles were found to accurately predict etiology across four distinct brain injuries, including CT-negative. Serum markers GFAP and UCHL1 may be helpful for classifying the nature of brain injury, which will aid with prognostication and development of therapeutics.

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“…PLR < 25%). Finally, high levels of serum biomarkers for brain injury, such as neuron specific enolase (NSE) and protein S-100β, have reported in COVID-19 patients ( DeKosky et al, 2020 ); their daily measurement could be discussed then at the medical round by the nursing team in patients with suspected brain injury if not prescribed by the attending doctors.…”

Section: How Nurses Can Adequately Use Neuromonitoring At the Bedsidementioning

confidence: 99%