Study suggests hospitalized COVID-19 patients have elevated Alzheimer's-related biomarkers

Neurological symptoms have been widely reported in patients with coronavirus disease 2019 (COVID-19) and in those who have recovered from it. A new study led by Thomas Wisniewski of New York University Grossman School of Medicine, USA, finds that patients hospitalized with COVID-19 are more likely to have elevated biomarkers levels indicative of age-related neurodegeneration.

The researchers write:

We identified elevations across a spectrum of CNS specific markers, including neuronal (total tau, UCHL1), and astrocytic/glial markers (GFAP), as well as AD-related markers (pTau181).”

Neuronal, glial, and neurodegenerative biomarkers were significantly higher in patients with COVID-19 diagnosed with encephalopathy. These biomarkers were also associated with more severe COVID-19 illness and worse rates for hospital discharge.

In the study, patients with COVID-19 had no history of dementia. Yet, they showed higher neurodegenerative biomarkers — NFL, GFAP, and UCHL1 — than patients with Alzheimer’s.

The study “Elevation of Neurodegenerative Serum Biomarkers among Hospitalized COVID-19 Patients” is published in the medRxiv* preprint server.

Patient characteristics

The study evaluated neurodegenerative biomarkers from 251 patients hospitalized for COVID-19 infection with no dementia or cognitive impairment history. The average age of the patient was 71 years. About 31% of hospitalized patients with COVID-19 needed mechanical ventilation, 25% died, and 53% were successfully discharged.

The number of biomarker samples that were evaluated for the study differed based on the biomarker being measured. For example, there was 246 neurofilament light (NFL) biomarker samples but 120 samples measuring the Aβ-42 biomarker.

There were 161 participants without COVID-19 infection who served as controls for the study. Fifty-four participants had no cognitive impairments, another 54 had mild cognitive impairment, and 53 had Alzheimer’s disease.

Elevated biomarker levels are seen in hospitalized COVID-19 patients, regardless of neurological symptoms

About 48% of patients with COVID-19 experienced neurological symptoms. Sixty-three percent were diagnosed with toxic-metabolic encephalopathy, and 46% had hypoxic/ischemic brain injury.

Patients with COVID-19 were more likely to experience elevations in neurodegenerative biomarkers. This increase in biomarker levels was significantly associated with being of older age and having severe COVID-19.

Patients with severe COVID-19, such as those with low oxygen levels and requiring mechanical ventilation, were strongly associated with higher total tau, pTau181, and NFL levels. There were also significant correlations between elevated ptau-181, NFL, GFAP and admission D-Dimer levels.

Patients who did not exhibit neurological symptoms also showed elevated levels of total tau, ptau181, NFL, and UCHL1.

Neurodegenerative biomarker levels for tau, ptau181, GFAP, and NFL were especially high in patients with COVID-19 diagnosed with toxic-metabolic encephalopathy.

Correlations observed between high biomarker levels and survival

Patients who died in the hospital had significantly higher neurodegenerative biomarker levels than patients who lived. Additionally, patients who were discharged had lower total tau, NFL, and GFAP biomarker levels than patients who continued to be hospitalized.

Having elevated Aβ-40 and Aβ-42 levels were not associated with toxic-metabolic encephalopathy, dying in the hospital, or getting discharged.

The ratio of pTau181/Aβ42 was significantly correlated with toxic-metabolic encephalopathy and in-hospital death. A patient’s ratio of Aβ42/40 levels and higher serum Aβ-40 levels was linked to a greater chance of getting discharged.

Patients with COVID-19 show more neurodegenerative biomarkers than patients with Alzheimer’s

Patients with COVID-19 showed higher NFL and GFAP levels than patients with Alzheimer’s disease and no history of COVID-19. These biomarker levels were also more elevated than in patients with mild or no cognitive impairment.

UCHL1 biomarker levels were significantly more elevated in patients with COVID-19 than patients with mild cognitive impairment. Conversely, though, these levels were similar among patients with Alzheimer’s.  

Overall, the study suggests SARS-CoV-2 infection is significantly correlated with elevated neurodegenerative biomarkers. However, more studies tracking biomarker levels in patients who recover from COVID-19 are needed to better understand how this ties into cognitive issues observed in long COVID.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Jocelyn Solis-Moreira

Jocelyn Solis-Moreira graduated with a Bachelor's in Integrative Neuroscience, where she then pursued graduate research looking at the long-term effects of adolescent binge drinking on the brain's neurochemistry in adulthood.