A Novel Combination of Blood Diagnostic Biomarkers Identify Neuro Post-Acute Sequalae of COVID-19 with 90% Accuracy
George Tachas1, Barbara Hanson2, Lavanya Visvabharathy3, Igor Koralnik4, Advait Padhye1
1Percheron Therapeutics Ltd, 2Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA, 3Biological Science Division, University of Chicago, IL 60637, USA, 4Northwestern University
Objective:
The aim was to investigate the plasma proteomics of people diagnosed with neurological manifestations of Long COVID, also called neuro Post-Acute Sequelae of COVID-19 (neuro-PASC) to identify blood diagnostic and therapeutic biomarkers of neuro-PASC. 
Background:

SARS-CoV-2 responsible for coronavirus disease 2019 (COVID-19) caused a global pandemic, with over 103 million infections and more than a million deaths in the US.  Long Covid, a Post-Acute Sequelae of COVID-19 (PASC), is a multi-systems syndrome currently affecting 14 million people in the US, and neuro-PASC are among the most debilitating, and prevalent long-lasting manifestations.

Design/Methods:

Plasma samples from 48 non-hospitalized Neuro-PASC patients with diagnosed neurological symptoms (NP), 20 convalescent control (CC) subjects, and 24 unvaccinated healthy control (HC) subjects, was used to generate data on over 7,000 proteins using the Somascan® proteomics platform, analysed using Dataviz® software to perform statistical analysis and using box plots. The NP, CC, and HC groups were assessed by T-tests, U-Tests, ANOVA and Kruskalis Wallis tests at a Bonferroni p <0.05 and using a Benjamini-Hochberg corrected False Discovery Rate at <0.01.

Results:

Assessment identified biomarkers that differentiated Neuro-PASC patients from control subjects, with 3 biomarkers, C5a, TGFβ1, Gliomedin, expressed highly in blood diagnosing neuro-PASC with 94% sensitivity and 86% specificity which is a 90% accuracy suitable for development. 3 additional biomarkers Gal3ST1, IFN lambda-1, and GHRH improved accuracy to 92%, and a combination of 5 more biomarkers, LFA-3, FASLG/Transgelin-1, and GPNMG/IGFH1 improved accuracy to close to 100%. These markers suggest neuroprotective-degenerative, viral-pathogen, vascular-adipose, clotting-platelet, autoimmune (inflammatory, fibrosis, integrin, antigen presentation) pathways are involved in neuro-PASC pathogenesis. A dozen partly overlying biomarkers were modulated to which there are FDA approved drugs.

Conclusions:

Through an agnostic proteomics approach, aberrant pathways in neuro-PASC were identified for diagnostics which in combination with clinical assessment can be used to personalize treatments with registered and existing novel drugs. 

10.1212/WNL.0000000000212354
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