Plasma biomarkers of neurodegeneration and neuroinflammation in hospitalized COVID‐19 patients with and without new neurological symptoms

Abstract

BackgroundThe COVID‐19 pandemic is an unprecedented global health care crisis. Older individuals and those with pre‐existing AD/ADRD or mild cognitive impairment are at increased risk of SARS‐CoV‐2 infection, with a higher mortality. In this study we assessed that the presence of plasma biomarkers associated with AD, neurodegeneration and neuroinflamation in older patients (>60yrs old), who were hospitalized with COVID‐19, who either had or did not have new neurological symptoms associated with infection.MethodPatients were admitted to New York University Langone Health (NYULH), with sites in Manhattan, Brooklyn and Long Island. All patients were positive for SARS‐CoV‐2 infection. Plasma from 310 patients were analyzed (158 were tested positive for SARS‐CoV‐2 with neurological symptoms and 152 were positive for SARS‐CoV‐2 without neurologic symptoms). Plasma biomarkers assays (total tau [t‐tau], neurofilament light [NfL], glial fibrillary acid protein [GFAP], ubiquitin carboxyl‐terminal hydrolase L1 [UCH‐L1] Aβ40, Aβ42 and pTau‐181) were performed at the Biomarker Core of NYU ADRC using the SIMOA SR‐XResultThe levels of t‐tau, NfL, GFAP, and UCH‐L1 were measured using the Neurology 4‐plex A and showed a significant elevation in COVID‐19 patients with neurologic symptoms compared to COVID‐19 patients without neurological symptoms: NfL (two tailed t‐test p = 0.0003), GFAP (two tailed t‐test p = 0.0098), UCH‐L1 (two tailed t‐test p = 0.0138) and t‐tau (two tailed t‐test p = 0.04). pTau 181 was also elevated in COVID‐19 subjects with neurological symptoms (two tailed t‐test p = 0.0141). There were no significant differences with Aβ1‐40 (two tailed t‐test p = 0.33). Both Aβ1‐42 and the pTau/ Aβ42 ratio showed a significant differences in patients with neurological symptoms (two tailed t‐test p = 0.049 and p = 0.0017, respectively).ConclusionSerum biomarkers of neuronal injury, neuroinflammation and Alzheimer’s disease such as NfL, t‐tau, UCH‐L1, GFAP and pTau‐181 correlate strongly with the presence of neurological symptoms in COVID‐19 patients. These findings indicate that patients who had COVID‐19 may have an acceleration of AD/ADRD symptoms and pathology.