PT  - JOURNAL ARTICLE
AU  - Barbara A. Hanson
AU  - Lavanya Visvabharathy
AU  - Sareen T. Ali
AU  - Anthony K. Kang
AU  - Tulsi R. Patel
AU  - Jeffrey R. Clark
AU  - Patrick H. Lim
AU  - Zachary S. Orban
AU  - Soyoon S. Hwang
AU  - Dawn Mattoon
AU  - Ayush Batra
AU  - Eric M. Liotta
AU  - Igor J. Koralnik
TI  - Plasma Biomarkers of Neuropathogenesis in Hospitalized Patients With COVID-19 and Those With Postacute Sequelae of SARS-CoV-2 Infection
AID  - 10.1212/NXI.0000000000001151
DP  - 2022 May 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e1151
VI  - 9
IP  - 3
4099  - http://nn.neurology.org/content/9/3/e1151.short
4100  - http://nn.neurology.org/content/9/3/e1151.full
SO  - Neurol Neuroimmunol Neuroinflamm2022 May 01; 9
AB  - Background and Objectives Although patients hospitalized with COVID-19 frequently present with encephalopathy, those with mild initial COVID-19 disease who never required hospitalization also often develop neurologic symptoms as part of postacute sequelae of severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection (neuro-PASC). The pathogenic mechanisms of COVID-19 encephalopathy and neuro-PASC are unknown. We sought to establish biochemical evidence of CNS injury in those patients and their association with neuropsychiatric manifestations and SARS-CoV-2 antigenemia.Methods We recruited hospitalized, posthospitalized, and nonhospitalized patients with confirmed diagnosis of COVID-19 with neurologic symptoms in addition to healthy control (HC) subjects. Plasma neurofilament light chain (pNfL), plasma glial fibrillary acidic protein (pGFAP), and plasma SARS-CoV-2 Nucleocapsid antigen (pN Ag) were measured by HD-X Simoa analyzer (Quanterix) and compared with neuropsychiatric symptoms, patient-reported quality-of-life measures, and standardized cognitive assessments. Neuroglial scores (pGFAP/pNfL) were calculated to estimate the relative contribution of astroglial and neuronal involvement.Results We enrolled a total of 64 study participants, including 9 hospitalized patients with COVID-19 encephalopathy (CE), 9 posthospitalization neuro-PASC (PNP) patients, 38 nonhospitalized neuro-PASC (NNP) patients, and 8 HC subjects. Patients with CE were older, had higher pNfL and pGFAP concentrations, and more frequent pN Ag detection than all neuro-PASC groups. PNP and NNP patients exhibited similar PASC symptoms, decreased quality-of-life measures, and cognitive dysfunction, and 1 of the 38 (2.6%) NNP patients had pN Ag detectable 3 weeks postsymptoms onset. Patients with neuro-PASC presenting with anxiety/depression had higher neuroglial scores, which were correlated with increased anxiety on quality-of-life measures.Discussion pNfL, pGFAP, and pN Ag measurements indicate neuronal dysfunction and systemic involvement in hospitalized COVID-19 patients with encephalopathy. Detection of SARS-CoV-2 N Ag in blood 3 weeks after symptoms onset in a nonhospitalized patient suggests that prolonged antigenic stimulation, or possibly latent infection, may occur. Anxiety was associated with evidence of astroglial activation in patients with neuro-PASC. These data shed new light on SARS-Cov-2 neuropathogenesis and demonstrate the value of plasma biomarkers across the COVID-19 disease spectrum.CAT=computer adaptive testing; CE=COVID-19 encephalopathy; GLT-1=glutamate transporter 1; HC=healthy control; MS=multiple sclerosis; NMOSD=neuromyelitis optica spectrum disorder; NNP=nonhospitalized neuro-PASC; PASC=Postacute sequelae of SARS-CoV-2 infection; pGFAP=plasma glial fibrillary acidic protein; pNfL=Plasma neurofilament light chain; PNP=posthospitalization neuro-PASC; PROMIS=Patient-Reported Outcome Measurement Information System; RT-PCR=reverse transcriptase PCR; SARS-CoV-2=severe acute respiratory coronavirus type 2