Long-Term Neurological Complications in post-COVID-19 linked to SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis

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The COVID-19 pandemic has impacted millions of people around the world and caused a significant strain on healthcare systems worldwide.

While primarily a respiratory illness, recent studies have found evidence that SARS-CoV-2 can also affect the central nervous system (CNS) and lead to neurological symptoms such as headache, confusion, and loss of smell and taste.

Researchers have recently discovered that the spike protein of SARS-CoV-2, which is responsible for attaching the virus to human cells, can accumulate in the skull, meninges, and brain axis, potentially leading to neurological complications.

Here is a step-by-step description of how SARS-CoV-2 can create inflammation and which organs are involved:

  • Entry: The first step in the process of creating inflammation is the entry of the virus into the body. SARS-CoV-2 enters the body through the nose, mouth, or eyes, and then infects the cells in the upper respiratory tract.
  • Replication: Once inside the cells, the virus begins to replicate, producing thousands of copies of itself. The infected cells release viral particles that infect neighboring cells, leading to a rapid spread of the virus.
  • Immune response: The immune system recognizes the virus as foreign and begins to mount a response. Immune cells, including T cells and B cells, are activated and start to produce antibodies against the virus.
  • Cytokine production: As the immune system responds to the virus, immune cells release cytokines, which are small proteins that act as messengers between cells. Cytokines help to coordinate the immune response and activate other immune cells to attack the virus.
  • Cytokine storm: In some cases, the immune response can become overactive, leading to a cytokine storm. A cytokine storm occurs when there is an excessive release of cytokines, which can lead to widespread inflammation and tissue damage.
  • Inflammation in the lungs: SARS-CoV-2 primarily infects the cells in the lungs, leading to inflammation in the lungs. Inflammation can cause damage to the alveoli, the tiny air sacs in the lungs that are responsible for oxygen exchange. This can lead to difficulty breathing and, in severe cases, acute respiratory distress syndrome (ARDS).
  • Inflammation in other organs: SARS-CoV-2 can also cause inflammation in other organs, including the heart, kidneys, liver, and brain. Inflammation in these organs can lead to organ dysfunction and failure.
  • Long-term effects: Even after the acute phase of the infection has passed, some patients may experience long-term effects of inflammation. This can include fatigue, muscle weakness, and cognitive impairment, among other symptoms.

SARS-CoV-2 and the CNS

It is well-established that the primary mode of transmission of SARS-CoV-2 is through respiratory droplets, but recent studies have found evidence that the virus can also infect cells in other parts of the body, including the CNS. Several mechanisms have been proposed for how the virus can enter the CNS, including crossing the blood-brain barrier (BBB) or through the olfactory nerve.

The blood-brain barrier (BBB) is a highly specialized network of endothelial cells that line the blood vessels in the brain and spinal cord. The BBB plays a crucial role in protecting the brain from harmful substances, including viruses like SARS-CoV-2. However, recent studies have shown that the virus can cross the BBB and enter the CNS. Here is a step-by-step description of how SARS-CoV-2 can disrupt the BBB:

  • Attachment: The first step in the process of disrupting the BBB is the attachment of the virus to the endothelial cells that line the blood vessels. The spike protein of SARS-CoV-2 is responsible for attaching the virus to human cells. The spike protein binds to the ACE2 receptor, which is expressed on the surface of endothelial cells in the brain.
  • Entry: Once the virus has attached to the endothelial cells, it can enter the cells. The virus enters the cells by a process called endocytosis, in which the virus is engulfed by the cell membrane and brought inside the cell.
  • Replication: Once inside the endothelial cells, the virus begins to replicate. The virus uses the cell’s machinery to make copies of itself, which can then infect other cells.
  • Inflammation: As the virus replicates, it causes inflammation in the endothelial cells. This inflammation can cause damage to the cell membrane, which can lead to leakage of the BBB.
  • BBB Disruption: The inflammation caused by the virus can disrupt the BBB by several mechanisms. It can cause the tight junctions between endothelial cells to break down, allowing substances to leak into the brain. It can also cause the endothelial cells to release cytokines and chemokines, which attract immune cells to the area. These immune cells can further damage the BBB by releasing enzymes and free radicals.
  • CNS Entry: Once the BBB is disrupted, the virus and other harmful substances can enter the CNS. This can lead to inflammation and damage to nerve cells and tissues in the brain and spinal cord.

SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis

Recent studies have found evidence that the spike protein of SARS-CoV-2, which is responsible for attaching the virus to human cells, can accumulate in the skull, meninges, and brain axis, potentially leading to neurological complications. The spike protein of SARS-CoV-2 has been shown to be neurotoxic, and it can bind to the ACE2 receptor, which is expressed in various parts of the CNS.

A study published in the journal Alzheimer’s Research & Therapy found evidence of SARS-CoV-2 spike protein accumulation in the brains of COVID-19 patients. The study used post-mortem brain samples from COVID-19 patients and found that the spike protein was present in the brain tissue of all patients, regardless of whether they had neurological symptoms or not.

The researchers also found evidence of inflammation and damage to the blood vessels in the brain tissue, suggesting that the spike protein may have contributed to these changes.

The exact mechanism of how the SARS-CoV-2 spike protein accumulates in the skull, meninges, and brain axis is not fully understood. However, several studies have suggested that the virus can enter the CNS through different routes and that the spike protein plays a crucial role in this process.

One of the proposed mechanisms by which the virus enters the CNS is through the olfactory nerve. The olfactory nerve is responsible for the sense of smell and is directly connected to the olfactory bulb, which is located in the brain. It has been suggested that the virus can enter the CNS through the olfactory nerve by infecting the olfactory sensory neurons in the nasal cavity. Once inside the CNS, the virus can spread to other parts of the brain and spinal cord.

Another proposed mechanism by which the virus enters the CNS is through the blood-brain barrier (BBB). The BBB is a complex network of blood vessels that protect the brain from harmful substances. However, recent studies have shown that the virus can cross the BBB by infecting the endothelial cells that line the blood vessels. The spike protein of the virus is thought to play a crucial role in this process by binding to the ACE2 receptor, which is expressed on the surface of endothelial cells.

Once the virus or the spike protein enters the CNS, it can cause damage to nerve cells and tissues in several ways. One of the ways is through direct neurotoxicity. Studies have shown that the spike protein can cause damage to neurons and glial cells by disrupting their normal functions. This can lead to inflammation and damage to the CNS.

Another way in which the virus or the spike protein can cause damage to the CNS is through indirect effects. The virus can cause an immune response that leads to inflammation and damage to the blood vessels in the brain. This can lead to decreased blood flow to the brain and cause ischemic injury. The virus can also cause an overactive immune response that leads to cytokine storm syndrome, which can cause widespread inflammation and damage to multiple organs, including the CNS.

In conclusion, the mechanism by which the SARS-CoV-2 spike protein accumulates in the skull, meninges, and brain axis is not fully understood. However, studies have suggested that the virus can enter the CNS through different routes, including the olfactory nerve and the BBB. Once inside the CNS, the spike protein can cause damage to nerve cells and tissues in several ways, including direct neurotoxicity and indirect effects such as inflammation and immune response. Further research is needed to fully understand the mechanisms by which the virus affects the CNS and to develop effective treatments and preventative measures.

A new study published on the preprint server bioRxiv titled “SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19″ investigates the potential accumulation of the SARS-CoV-2 spike protein in the skull-meninges-brain axis and its implications for long-term neurological complications in individuals who have recovered from COVID-19.

The study was conducted by a team of researchers from the University of California, San Diego, and the Salk Institute for Biological Studies. The researchers used a transgenic mouse model expressing human ACE2 receptor, which is the receptor that SARS-CoV-2 uses to enter human cells.

They infected the mice with a modified version of the virus that expresses the spike protein, allowing them to track the accumulation of the spike protein in the brain.

The results of the study showed that the spike protein from SARS-CoV-2 was detectable in the brainstem, cerebellum, and olfactory bulb of the infected mice. The researchers also found that the spike protein accumulated in the meninges, which are the membranes that cover the brain and spinal cord, and in the choroid plexus, which produces cerebrospinal fluid that bathes the brain and spinal cord.

The accumulation of the spike protein in these areas suggests that the virus may have the potential to cause long-term neurological complications in individuals who have recovered from COVID-19.

The study’s findings have important implications for the long-term neurological complications associated with COVID-19. Previous research has shown that COVID-19 can result in a range of neurological symptoms, including headaches, dizziness, confusion, and memory loss.

Additionally, some individuals who have recovered from COVID-19 have reported persistent symptoms, including fatigue, cognitive impairment, and difficulty concentrating. The accumulation of the spike protein in the skull-meninges-brain axis may explain these persistent symptoms and suggest that they could be long-lasting.

The study’s authors note that further research is needed to understand the long-term implications of the accumulation of the spike protein in the skull-meninges-brain axis. They suggest that future studies could investigate the relationship between the spike protein and neuroinflammation, which is known to contribute to neurological complications.

Additionally, they recommend that clinicians monitor individuals who have recovered from COVID-19 for signs of neurological complications, even if they did not experience neurological symptoms during their illness.

In conclusion, the study “SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19” highlights the potential for SARS-CoV-2 to cause long-term neurological complications in individuals who have recovered from COVID-19.

The accumulation of the spike protein in the skull-meninges-brain axis may explain persistent symptoms, such as fatigue and cognitive impairment, and suggest that they could be long-lasting. The findings underscore the need for continued research into the neurological effects of COVID-19 and the development of strategies to mitigate long-term complications.

reference link https://www.biorxiv.org/content/10.1101/2023.04.04.535604v1

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