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

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

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.

Keywords: CNS injury; COVID-19; GFAP, SARS-CoV-2; UCH-L1; blood biomarkers.

Conflict of interest statement

Ronald L. Hayes owns stock in, receives compensation from, and is an executive officer of Banyan Biomarkers, Inc. and as such may benefit financially as a result of the outcomes of this research or work reported in this publication. Nancy D. Denslow was a founder of the company and currently serves on the Board of Directors of Banyan Biomarkers, Inc. that has developed assays for biomarkers for traumatic brain injury. These biomarkers may be of interest to identify brain damage from COVID-19. Steven DeKosky chairs medical advisory boards for Acumen Pharmaceuticals and Cognition Therapeutics and chairs the Drug Safety Monitoring Boards for Biogen, Prevail Pharmaceuticals, and Vaccinex, Inc. He is editor of the Section on Dementia for Up-To-Date, a point of care electronic textbook, and Associate Editor of Neurotherapeutics, the journal of the American Society for Experimental Neurotherapeutics. None of them have any conflicts with the manuscript or its contents. Michael D. Davis is a Co-Founder of Airbase Breathing Company. Ruchira M. Jha is a paid consultant/on the Advisory Board for Biogen. Robert D. Welch will be doing a seminar for Abbott Labs, Inc. regarding a point-of-care test for GFAP and UCH-L1 and he previously (not since 2017) received contract research funding from Banyan Biomarkers, Inc.

Figures

FIG. 1.
FIG. 1.
Generalized schematic of a clinical research study of BBs of CNS Injury in COVID-19 patients. BBs, blood biomarkers; CNS, central nervous system; COVID-19, coronavirus disease 2019; EHR, electronic health record; FDA, U.S. Food and Drug Administration; ICU, intensive care unit; IRB, institutional review board.

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