The blood-brain barrier (BBB) protects the brain from harmful molecules and infections. COVID-19 and the Long COVID syndrome have neurologic and psychiatric effects. This article presents three studies that show evidence that the spike protein of SARS-CoV-2 can cross the BBB and wreak havoc by itself.
Endothelial cells line the inside of the BBB, and they have tight junctions to prevent germs and toxic molecules from reaching the brain.
However, in conditions like COVID-19, viruses can pass through the BBB and affect brain function. The study’s question is how SARS-CoV-2 gets across the BBB and how it affects brain function.
The study by Kim and colleagues from South Korea found that the S1 domain of the spike protein can pass through the BBB faster than the whole spike protein. The S1 and S2 subunits form the spike protein.
The S1 contains the receptor-binding domain the virus uses to stick to the ACE2 and other host receptors.
Proteases can cut the spike proteins into the S1 and S2 subunits. [2] In the study [Kim et al., 2021], the S1 subunit does not have to be attached to the whole SARS-CoV-2 to cause damage.
The S1 enters the cells in a different way. Typically, the SARS-CoV-2 uses the ACE2 receptors. In their experiment, the S1 and the whole spike protein can enter the cells using the endosomes.
Endosomes are from the cells’ outer lining. They internalize harmful molecules and bring them inside the cells. The image below shows how the endosomes form in the endocytic pathway. Their final destination is the lysosome, which destroys harmful substances.
In the case of the spike proteins, instead of the lysosomes, the spike proteins end in the mitochondria.
Spike proteins damage the mitochondria.
The mitochondria are the power source of cells. The endothelial cells of the brain have more mitochondria than the skeletal muscles due to their higher energy demand. Kim and others found that the S1 disrupts the mitochondria more than the whole spike protein.
Kim’s team’s findings about the spike proteins’ penetration of the blood-brain barrier and damage to the mitochondria made them express their concerns about the COVID vaccines.
Moreover, our data can also provide valuable information for the assessment of safety in COVID-19 vaccines because most of them utilize the spike protein as an epitope to induce immune responses. Our study provides the arguments that the spike protein can induce
changes in the normal physiology of the brain endothelial cells.
A study [Kowarz et al., 2021] showed that variant spike proteins could be produced by human cells during the RNA splicing of the COVID vaccines. Those variant spike proteins can go with the bloodstream and cause inflammation and thrombosis wherever they go. [3]
RNA splice study shows why AstraZeneca and Janssen jabs are clot shots
Spike proteins induce inflammation in the brain
The second study [Buzhdygan et al.] is an in vitro experiment and also found that the S1 protein subunits tested on human brain microvascular cells could disrupt the blood-brain barrier. [4]
Moreover, the entry of the spike proteins triggers a pro-inflammatory response in the lining of the blood vessels, resulting in blood-brain barrier dysfunction. A permeable blood-brain barrier starts a vicious cycle that allows more viral particles and infected immune cells into the brain to cause further disruption of the BBB and brain inflammation.[4]
Typically, the SARS-CoV-2 virus attaches to the ACE2 receptor with its receptor-binding domain (RBD) on the S1 subunit to gain entry to the cells, as previously mentioned.
Buzhdygan and his group from Temple University also found that the entry of the SARS-CoV-2 virus is independent of the ACE2 receptors since the S2 subunit could also enter the blood-brain barrier. [4]
More ACE2 is present in people with hypertension and dementia.
The research also showed for the first time that people with chronic high blood pressure and Alzheimer’s dementia have more ACE2 receptors in their cerebral blood vessels. [4] and explains why they are more at risk for developing worse COVID-19 outcomes. Some Alzheimer’s dementia patients who survive COVID have worse dementia after the acute illness.
If the part of the brainstem that controls involuntary breathing is disrupted, poor ventilation and low oxygen levels result. Once this happens, the patient needs a breathing machine (mechanical ventilator) to survive.
In Long COVID syndromes, the effect on the brain gives a sensation of shortness of breath, especially with exertion.
Spike proteins spread all over the brain.
The third study by Rhea and colleagues from Oregon, USA, was done in mice. They administered S1 spike protein radiolabeled with iodine from the nose in one group and into the vein in another. [5]
Radiolabeling uses X-rays to detect minute quantities of iodinated S1 protein (I-S1) in different parts of the brain. The radiolabeling makes the I-S1 protein “glow in the dark.”
Both groups’ spike proteins were able to enter the BBB. The mechanism of the spike protein entry into the cells is called adsorptive transcytosis, similar to the endocytic pathway that uses the endosomes found by Kim’s group.
Then, they looked at the spread of the radiolabeled Spike 1 protein. The spike protein levels were initially higher in the olfactory bulb and the hypothalamus. Eventually, in 30 minutes, the S1 proteins reached the eleven regions of the brain.
The graph below shows the eleven brain parts where the spike proteins were detected. The FCtx is the Frontal cortex, PCtx is the Parietal cortex, and OCtx is the Occipital cortex.
Significance: The uptake in all brain regions explains encephalitis (brain inflammation), respiratory difficulties, and loss of smell during acute COVID-19.
The figure below shows the areas of the different cortices of the brain.
The image below shows the functions of each part of the lobes. A lobe’s malfunction will present problems in the processes it controls. For example, a defect in the motor association area can present as weakness in an arm or leg.
Take Away Message
In summary, all three studies show that the spike protein and its smaller subunits like the S1 and S2 can cross the protective blood-brain barrier and spread to the whole brain. Compromise of the blood-brain barrier diminishes brain function by inflammation and loss of cellular energy by disrupting the mitochondria.
The breakdown of the blood-brain barrier, loss of power supply to cells, and inflammation contribute to the symptoms of severe acute COVID-19, which require intensive unit care.
Some people who have mild to moderate COVID-19 may continue to develop symptoms of COVID-19 long after the acute illness is over. This is called Long COVID or Post Acute Sequelae of COVID-19 (PASC). Research from Pennsylvania State University said that more than half of people with COVID might develop PASC.
Yale Medicine lists the symptoms of Long COVID. Among the symptoms associated with brain functions are:
-
- Fatigue
- Headache
- Shortness of breath (the brain controls automatic breathing)
- Persistent loss of smell and taste
- Joint pain; muscle aches and pain/weakness
- Memory loss
- Brain fog (difficulty concentrating, sense of confusion or disorientation)
- Dizziness
- Low-grade, intermittent fever
- Rapid or irregular heartbeat (palpitations), the brain has control of the heart
- Anxiety
- Depression
- Post-traumatic stress disorder (PTSD)
- Insomnia
- Earache, hearing loss, and ringing in ears (tinnitus)
- Diarrhea, nausea, and abdominal pain
- Diminished appetite
The ability of the S1 and S2 subunits to pass through the blood-brain barrier and cause damage also raises concern that some people who get the COVID shots may develop neurological symptoms and complications arising from brain dysfunction.
If people who test positive for SARS-CoV-2 receive early treatment, replication and spread are prevented, and possibly, severe COVID-19 and Long COVID can be prevented.
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Related:
- Persistent inflammation explains Long COVID syndrome.
- SARS-CoV-2 brings out an endogenous retrovirus protein to cause severe COVID-19 and Long COVID syndrome.
- 13 ways that the SARS-CoV-2 spike protein causes damage
- SARS-CoV-2 spike proteins detected in the plasma following Moderna shots
- The SARS-CoV-2 spike protein can form amyloids seen in lung, blood, and nervous system disorders
- UK Study of COVID-19 shots and Excess Rates of Guillain-Barré Syndrome
- Guillain-Barre Syndrome After Covid-19 Vaccination
- The High Risk of Deadly Brain Clots in the J & J COVID Vaccine
- Shingles after COVID-19 Vaccination
- Pulmonary Hypertension, Heart Disease, and Stroke from SARS-CoV-2 Spike Protein Cell Signaling
References:
- Kim, E.S. et al. Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells. Viruses 2021, 13, 2021. https://doi.org/10.3390/v13102021
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Annual Review of Virology 2016 3:1, 237-261
- Kowarz E, Krutzke L, Reis J, et al. “Vaccine-Induced Covid-19 Mimicry” Syndrome: Splice reactions within the SARS-CoV-2 Spike open reading frame result in Spike protein variants that may cause thromboembolic events in patients immunized with vector-based vaccines. Research Square; 2021. DOI: 10.21203/rs.3.rs-558954/v1
- Buzhdygan TP et al. The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier. Neurobiol Dis. 2020 Dec;146:105131. doi: 10.1016/j.nbd.2020.105131. Epub 2020 Oct 11. PMID: 33053430; PMCID: PMC7547916.
- Rhea, E.M., Logsdon, A.F., Hansen, K.M., et al. The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice. Nat Neurosci 24, 368–378 (2021). https://doi.org/10.1038/s41593-020-00771-8
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