- A study demonstrated that participants hospitalized with COVID-19 experiencing neurological complications had higher levels of blood proteins or biomarkers associated with neurological damage than people with Alzheimer’s.
- Increased biomarker levels correlated with COVID-19 severity, mortality risk, and the presence of neurological disorder.
- Long-term follow-up is necessary to determine if biomarker elevation is associated with an increased risk of developing subsequent neurodegenerative disorders.
COVID-19, the disease that a SARS-CoV-2 infection causes, often brings on mild upper respiratory symptoms. However, some individuals may experience severe illness requiring hospitalization. This can occur due to pneumonia and lung damage causing respiratory failure.
In addition, neurological manifestations commonly occur in people hospitalized with COVID-19. Neurological disorders may include encephalopathy, seizures, stroke, encephalitis, Guillain-Barré syndrome, and acute demyelinating encephalomyelitis.
Researchers at NYU Grossman School of Medicine conducted a study that investigated whether people with COVID-19 experiencing new-onset neurological complications during hospitalization had elevated blood markers indicating neurological damage.
The investigators published study results in the journal Alzheimer’s and Dementia.
Dr. Thomas Wisniewski, M.D., a co-author of the study, professor of neurology, pathology, and psychiatry, and director of both the NYU Alzheimer’s Disease Research Center and the Center for Cognitive Neurology, spoke about the study in an MNT interview.
He explained: “It’s clear that the [SARS-CoV-2] virus has a propensity for inducing vascular damage, targeting in the endothelial cells, and causing disruption of the blood-brain barrier, as well as inducing generalized neuroinflammation. Cytokines like interleukin 6 and interleukin 1 are much elevated in [individuals with COVID-19], and these are cytokines that drive neurodegeneration and Alzheimer’s disease.”
Cytokines are proteins that help the body’s cells to communicate.
Dr. Wisniewski added, “In our study, we became interested in looking at these types of biomarkers, [since these biomarkers] are what we follow in our Alzheimer’s disease research center for looking at the progression of Alzheimer’s-related pathology and other neurodegenerative disorders.”
Neurodegenerative biomarkers
In an interview with MNT, Jennifer Bramen, Ph.D., a senior research scientist at the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in the study, described the seven biomarkers the study measured:
- Total tau and pTau181 are indicators of neuron damage. Their levels increase as AD progresses. In AD, abnormal proteins form tangles, blocking the communication between brain cells, she explained.
- Ubiquitin C-terminal hydrolase L1 (UCHL1) is an enzyme that breaks down unnecessary proteins in brain cells. Brain injury or neurodegenerative diseases such as AD cause levels of UCHL1 to increase.
- Increased glial fibrillary acidic protein (GFAP) levels indicate damage to the glial cells. Glial cells help maintain the health of brain cells and the blood-brain barrier, which filters toxic substances.
- Neurofilament light chain (NfL) measures damage to axons of myelinated neurons. The axon is the part of the neuron that conducts electricity, and myelin is the insulation surrounding the neuron.
- Amyloid-β (Aβ) 40 and 42 are proteins that build up and cause the formation of amyloid plaques in AD, which disrupt brain cell function and communication.
- Lastly, a person’s pTau181 to Aβ42 ratio may identify early stages of AD.
Investigators also attempted to determine the association of increased biomarkers with rates of discharge to home and in-hospital death rates.
To assess the level of injury, the researchers compared serum biomarker levels of a control group of participants who had “normal” cognition, mild cognitive impairment (MCI), and AD with the biomarkers of people during hospitalization with COVID-19 and new neurological findings.
Researchers conducted a retrospective analysis of participants enrolled in the Study of Neurologic and Psychiatric Events in Acute COVID-19 (SNaP Acute COVID study), which examined serum samples people gave during their hospitalization for COVID-19.
Dr. Wisniewski explained, “We specifically excluded patients who have a preexisting cognitive disorder, any sort of dementia, or mild cognitive impairment, [to prevent clouding of the results].”
The SNaP Acute COVID study was a prospective study of 4,491 participants conducted in four New York hospitals between March 10 and May 20 of 2020, which evaluated the development of new neurological events during acute COVID-19 hospitalization.
The non-COVID control group comprised blood samples from the NYU Alzheimer’s Disease Research Center clinical core cohort banked before January 1, 2020. This was the date of the first reported COVID-19 cases in New York City. The researchers used validated testing tools — version three of the Uniform Data Set and the Clinical Dementia Rating — to stratify the control participants into three subgroups: normal cognitive functioning, MCI, and AD.
The study measured blood markers using an ultrasensitive testing methodology called single-molecule array technology.
The COVID-19 group consisted of 251 participants with a median age of 71. This group was 63% male. There were 161 participants in the control group with a median age of 71. Participants in the control group were 35% male.
The most common neurological complications included toxic metabolic encephalopathy (TME) in 63% of participants and brain injury due to reduced oxygen or blood flow in 46%.
Biomarker findings
The severity of COVID-19 correlated most strongly with total tau, pTau181, and NfL levels.
Higher GFAP and pTau181/Aβ-42 levels were associated with a significantly increased risk of death during hospitalization. Results showed that elevated levels of total tau, NfL, and GFAP corresponded to decreased discharge-to-home rates.
Those participants with COVID-19 who experienced new neurological events during hospitalization had significantly higher total tau, pTau181, NfL, and UCHL1, with the highest levels occurring in those with TME. The participants with COVID-19 had a 179% percent higher NfL, 73% higher GFAP, and 13% higher UCHL1 level than the AD group.
Dr. Wisniewski commented:
“In the study, we found very marked elevations of these seven biomarkers, indicating [the] significant presence of neurodegeneration, neuronal death, and gliosis. With marked neurodegeneration, neuroinflammation, and — at least at one time point — elevation of Alzheimer’s disease biomarkers, each […] correlated with the presence of neurological disease and the severity of infection as well as the outcome.”
Dr. Braman stated: “One limitation is that [the study] is only looking at hospitalized patients, so it’s still not clear if these biomarkers might be present in patients with less severe COVID-19 symptoms. Future research would be [needed] to understand how long lasting these effects are and how much they link up with actual cognitive deficits.”
Dr. Wisniewski agreed:
“We have been following these patients for 6 months and one year […] and there was the persistence of cognitive dysfunction [in up to 50% of these folks]. Hence, it’s important to follow this up. [P]erhaps biomarker findings speak of an increased risk of subsequent neurodegenerative disorders in this population.”
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