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

Steven T. DeKosky, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, Florida, USA.
Patrick M. Kochanek, Department of Critical Care Medicine, Department of Anesthesiology, Pediatrics, Bioengineering, and Clinical and Translational Science, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Alex B. Valadka, Department of Neurosurgery, Virginia Commonwealth University, Richmond, Virginia, USA.
Robert S. Clark, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Sherry H-Y Chou, Department of Critical Care Medicine, Neurology, and Neurosurgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Alicia K. Au, University of Pittsburgh, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Christopher Horvat, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Division of Pediatric Critical Care, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Ruchira M. Jha, Departments of Critical Care Medicine, Neurology, Neurological Surgery, Clinical and Translational Science Institute, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Follow
Rebekah Mannix, Department of Pediatrics and Emergency Medicine, Harvard Medical School, Department of Medicine, Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
Stephen R. Wisniewski, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Max Wintermark, Department of Neuroradiology, Stanford University, Stanford, California, USA.
Susan E. Rowell, Duke University School of Medicine, Durham, North Carolina, USA.
Robert D. Welch, Department of Emergency Medicine, Wayne State University School of Medicine, Detroit Receiving Hospital/University Health Center, Detroit, Michigan, USA.
Lawrence Lewis, Department of Emergency Medicine, Washington University in St. Louis, St. Louis, Missouri, USA.
Stacey House, Department of Emergency Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Rudolph E. Tanzi, Genetics and Aging Research Unit, Massachusetts General Hospital, McCance Center for Brain Health, Massachusetts General Hospital, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Department of Neurology (Research), Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Charlestown, Massachusetts, USA.
Darci R. Smith, Immunodiagnostics Department, Naval Medical Research Center, Biological Defense Research Directorate, Fort Detrick, Maryland, USA.
Amy Y. Vittor, Division of Infectious Disease and Global Medicine, University of Florida, Emerging Pathogens Institute, Gainesville, Florida, USA.
Nancy D. Denslow, Departments of Physiological Sciences and Biochemistry and Molecular Biology, University of Florida, Center for Environmental and Human Toxicology, Gainesville, Florida.
Michael D. Davis, Department of Pediatrics, Wells Center for Pediatric Research/Pulmonology, Allergy, and Sleep Medicine, Riley Hospital for Children at Indiana University, Indianapolis, Indiana, USA.
Olena Y. Glushakova, University of Virginia Cancer Center, Charlottesville, Virginia, USA.
Ronald L. Hayes, Banyan Biomarkers Inc., Alachua, Florida, USA.

Document Type

Article

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus attacks multiple organs of coronavirus disease 2019 (COVID-19) patients, including the brain. There are worldwide descriptions of neurological deficits in COVID-19 patients. Central nervous system (CNS) symptoms can be present early in the course of the disease. As many as 55% of hospitalized COVID-19 patients have been reported to have neurological disturbances three months after infection by SARS-CoV-2. The mutability of the SARS-COV-2 virus and its potential to directly affect the CNS highlight the urgency of developing technology to diagnose, manage, and treat brain injury in COVID-19 patients. The pathobiology of CNS infection by SARS-CoV-2 and the associated neurological sequelae of this infection remain poorly understood. In this review, we outline the rationale for the use of blood biomarkers (BBs) for diagnosis of brain injury in COVID-19 patients, the research needed to incorporate their use into clinical practice, and the improvements in patient management and outcomes that can result. BBs of brain injury could potentially provide tools for detection of brain injury in COVID-19 patients. Elevations of BBs have been reported in cerebrospinal fluid (CSF) and blood of COVID-19 patients. BB proteins have been analyzed in CSF to detect CNS involvement in patients with infectious diseases, including human immunodeficiency virus and tuberculous meningitis. BBs are approved by the U.S. Food and Drug Administration for diagnosis of mild versus moderate traumatic brain injury and have identified brain injury after stroke, cardiac arrest, hypoxia, and epilepsy. BBs, integrated with other diagnostic tools, could enhance understanding of viral mechanisms of brain injury, predict severity of neurological deficits, guide triage of patients and assignment to appropriate medical pathways, and assess efficacy of therapeutic interventions in COVID-19 patients.

Medical Subject Headings

Biomarkers (blood); Brain (metabolism, pathology); Brain Injuries (blood, diagnosis, etiology); COVID-19 (blood, complications, diagnosis); Humans; Nervous System Diseases (blood, diagnosis, etiology); Prospective Studies; Retrospective Studies

Publication Date

1-1-2021

Publication Title

Journal of neurotrauma

E-ISSN

1557-9042

Volume

38

Issue

1

First Page

1

Last Page

43

PubMed ID

33115334

Digital Object Identifier (DOI)

10.1089/neu.2020.7332

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