Blood diagnostic biomarkers for neurologic manifestations of long COVID

Background: SARS-CoV-2 responsible for COVID-19 caused a global pandemic, with billions of infections, millions of deaths and ongoing manifestations post COVID-19. "Long Covid", a Post-Acute Sequelae of COVID-19 (PASC), is an ongoing global healthcare problem, affecting all age groups, with many manifestations, and occurring despite vaccines and antivirals. Neurologic manifestations of PASC (Neuro-PASC) such as brain fog can last for years and are amongst the most debilitating and prevalent. There is a need for diagnostic tools and treatments. Methods: Plasma samples from 48 non-hospitalized PASC patients with diagnosed Neuro-PASC symptoms (NP), 20 convalescent control (CC) subjects, and 24 unvaccinated healthy control (HC) subjects, was used to generate data on over 7000 proteins using the SomaLogic® proteomics platform. ProViz® software was used to perform T-tests, U-Tests, ANOVA and Kruskalis-Wallis tests at a Bonferroni p < 0.05 and a Benjamini-Hochberg corrected False Discovery Rate <0.02, and box plots and knowhow used to identify diagnostic biomarkers and therapeutic targets. Results: C5a, TGFβ1, and Gliomedin, used together differentiated patients with Neuro-PASC from control subjects with 94 % sensitivity and 86 % specificity, a 90 % accuracy. Additional biomarkers, Gal3ST1, IFNλ1, and GHRH, improved accuracy to 94 %, and a combination of 5 more biomarkers, LFA-3, FASLG + Transgelin-1 and GPNMB + IGHG1, improved accuracy close to 100 %. These markers are suggestive of pathways involved in Neuro-PASC pathogenesis. A dozen partly overlying biomarkers were modulated to which there are FDA approved drugs. Conclusion: C5a, TGFβ1, Gliomedin expressed highly in serum could be developed as a diagnostic tool, and with clinical assessment used to personalize treatments with repurposed novel drugs.