Longitudinal changes of neurospecific serum proteins in COVID-19 patients

ABSTRACT

INTRODUCTION/HYPOTHESIS: COVID-19 has been associated with distinct types of neuronal damage. We hypothesize that the progression of neurological damage will be related to an imbalance between neurodegeneration, neuroinflammatory, and neuroprotective markers, therefore suggesting a potential mechanism for the emergence of adverse, chronic outcomes. METHODS: 105 patients admitted to an urban, academic hospital with a diagnosis of COVID-19 were enrolled. Serum neuroprotective (clusterin, fetuin), neurodegenerative (τ, phosphorylated τ, amyloids, TDP43, NRGN, NCAM-1, and KLK6), and neuroinflammatory (CCL23, YKL40, MIF) markers were collected. These were analyzed longitudinally in conjunction with immune system activators (RAGE, IL-34) using the multiplex platform. Electronic medical records were used to collect demographic and clinical data. RESULTS: Of the 105 patients, 5 were diagnosed with stroke within 28 days of admission, followed by an additional 6 strokes occurring by 6 months, or a 9.5% occurrence of stroke overall. Serum levels of Amyloid β42 declined significantly for the general population 7 days after admission when compared to initial collections (p< 0.001), while Amyloid β40, KLK6, and MIF declined and recovered within the same 7 days (p< 0.001, p< 0.001, p=0.003). The neuroprotective markers fetuin and clusterin were particularly dynamic with fetuin decreasing and restoring in less than 7 days (p=0.02) and clusterin remaining low after admission (p< 0.001). Most patients had persistently elevated CCL23 levels, with the stroke patient cohort having the highest values (p=0.018). The IL-6 levels of stroke patients were significantly higher compared to their non-stroke counterparts one week after admission (p=0.001), while IL-8 levels fluctuated before declining (p< 0.001). CONCLUSIONS: Our data reveals elevations in neuronal damage in the 7 days following hospital admission for COVID-19 patients. The down-regulation of fetuin and clusterin is particularly compelling as their declines may be linked to the elevated neuronal injury seen with increased neuroinflammatory markers, specifically CCL23 and IL-6. Serum levels of neurodegeneration markers proved complex, therefore possibly suggesting a more dynamic relationship to the neural abnormalities seen in COVID-19 patients.