When it comes to COVID-19 symptoms and outcomes, a lot of attention is paid to things like pneumonia, cytokine storms, blood clots, and breathing problems. That’s understandable – these are pressing, immediate concerns that impact survivability. However, there is mounting evidence that the novel coronavirus now affecting the world is creating impacts that will last far, far longer. In addition to permanent heart damage, some patients have also experienced neurodegeneration as a result of COVID-19.

What Is Neurodegeneration?

According to the EU Joint Programme – Neurodegenerative Disease Research, neurodegenerative disease

"is an umbrella term for a range of conditions which primarily affect the neurons in the human brain. Neurons are the building blocks of the nervous system, which includes the brain and spinal cord. Neurons normally don’t reproduce or replace themselves, so when they become damaged or die, they cannot be replaced by the body. Examples of neurodegenerative diseases include Parkinson’s, Alzheimer’s, and Huntington’s disease."

What Causes Neurodegeneration?

While there are several hundred classified neurodegenerative diseases, the underlying causes remain largely unknown. According to the authors of a study published in the Journal of Clinical Investigation,

"With few exceptions, the causes of neurodegenerative diseases are essentially unknown, and even when they have been identified, the mechanisms by which they initiate the disease remain, at best, speculative. For example, while the etiology of Huntington’s disease was identified more than two decades ago, we still do not know with certainty how the mutant huntingtin provokes the disease."

Where does COVID-19 fit into this picture? Right in the center of things, actually. According to research by Valina Dawson, published in May 2020,

"Among the first symptoms of COVID-19 is the loss of smell and taste, and there are reports of people in recovery struggling with cognitive impairment or stroke. According to researchers, these symptoms could be caused by neurons degenerating or damage to blood vessels that feed the brain."

At least one clinical trial is underway currently to study neurodegeneration markers and neurological courses in COVID-19-positive patients, as well. According to the description listed with the US National Library of Medicine,

"Most COVID-19 patients with neurologic impairment displayed expected complications of severe infections (e.g. neuropathy and muscle loss, stroke) but encephalitis remained exceptional, as previously observed in SRAS. It is argued that central lesions may explain some of the clinical features ventilation failure, or disproportionate residual fatigue and cognition impairment in survivors of severe COVID infection. According to data obtained from various coronavirus infections in animals, the investigators ask if severe COVID infection in humans could be associated with sub-clinical encephalitis. This clinical trial examines highly sensitive blood biomarkers of brain dysfunction in correlation with late clinical outcome. Biomarkers are neurofilament light chain (NFL) and GFAP. Clinical outcomes are death, signs of central neurologic sequellae, and fatigue. Clinical examination and blood samples will be obtained at inclusion (d0), which is mostly the entrance in intensive care unit (ICU), at day 7 (between day 4 and exit from ICU) and at day 60."

Another study published in Alzheimer’s Research & Therapy in early June 2020 points out that neurodegeneration from COVID-19 is becoming more certain.

"Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease."

How Might Stem Cells Help Combat COVID-19-Related Neurodegeneration?

Stem cells are being researched for their use in treating a broad range of COVID-19-related conditions and symptoms, ranging from lung damage to stopping cytokine storms. However, it appears that they may also prove useful in battling neurodegeneration. The key here is the ability to ability to create astrocytes from stem cells. It also appears that astrocytes play a key role in neurodegeneration in the first place.

According to Shane Liddelow, Ph.D., a collaborator on a study involving the creation of astrocytes from stem cells,

"We observed in mice that astrocytes in inflammatory environments [such as that created by COVID-19] take on a reactive state, actually attacking neurons, rather than supporting them. We found evidence of reactive astrocytes in the brains of patients with neurodegenerative diseases, but without a human stem cell model, it wasn’t possible to figure out how they were created and what they were doing."

The study focused on introducing stem cells into the inflamed environment and studying their behavior. The new astrocytes secreted a toxin that killed neurons but also failed to perform their typical jobs, leading to dysfunction within the system and additional neuron death. While the results did not reverse neurodegeneration, they point the way toward new and potentially radical treatments for patients.

A Ray of Hope

While research is ongoing, there is hope to be found in stem cell therapy. Mesenchymal stem cells (MSCs) have been used for years to reduce inflammation and induce regeneration and healing. COVID-19’s neurological damage seems to stem largely from the inflammation the disease creates, affecting astrocytes, which in turn kill neurons, leading to neurodegeneration in the brain and central nervous system. With stem cell therapy, inflammation can be reduced. Stem cells can also be transformed into new astrocytes, which in turn can help improve the health of the CNS and the brain.

However, it should be noted that allogeneic stem cells show superior performance and regenerative capabilities to autologous stem cells. Rather than being sourced from the patient’s own body, allogeneic stem cells come from umbilical cord blood and tissue. They’re young, highly energetic, and free of damage that might trigger a negative immune system response.

With that being said, the FDA has not approved any stem cell therapy, so all such treatments should be regarded as experimental only.


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