Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia.

INTRODUCTION: Neurological complications among hospitalized COVID-19 patients may be associated with elevated neurodegenerative biomarkers. METHODS: Among hospitalized COVID-19 patients without a history of dementia (N = 251), we compared serum total tau (t-tau), phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and amyloid beta (Aß40,42) between patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions. COVID-19 patient biomarker levels were also compared to non-COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161). RESULTS: Admission t-tau, p-tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in-hospital, while t-tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non-COVID controls with MCI or AD. DISCUSSION: Neurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.

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

Background The 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. Method Patients 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] A?40, A?42 and pTau-181) were performed at the Biomarker Core of NYU ADRC using the SIMOA SR-X Result The 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 A?1-40 (two tailed t-test p = 0.33). Both A?1-42 and the pTau/ A?42 ratio showed a significant differences in patients with neurological symptoms (two tailed t-test p = 0.049 and p = 0.0017, respectively). Conclusion Serum 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.