[Preprint] SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications

That's a first sentence that might raise a few eyebrows from respiratory physicians, I'm not sure that that is what they meant.

I find this quite interesting. Viral persistence with long periods of latency would be a straightforward answer to the question 'what causes ME/CFS?'. I think it is possible.

A summary of previous evidence for persistence:

Whole body distribution of spike S1 protein in a mouse model
They fluorescently-labelled spike protein that binds to the mouse version of the ACE receptor and injected it into mice. After 30 minutes, they looked for the fluorescence. It sounds as though it was mostly in or very close to the blood vessels, as we might expect, but also in testes, ovaries and the brain and spinal column, skull marrow niches, in the channels connecting the skull marrow to the meninges, and other bone marrow niches (e.g.in the tibia and femur). Control proteins of the spike protein that binds to the human ACE receptor and a flu protein were not distributed throughout the body like this.

So, that tells us that the spike protein can get into most parts of mice pretty quickly, although it doesn't tell us about persistence.

 

SARS-CoV-2 infection in the human skull, meninges, and brain
They found viral spike protein in the skull marrow niches, skull marrow channels, and meninges of 17 patients who died during an acute Covid-19 infection and no viral spike protein in samples from control patients. They suggest that the spike protein leaked into the bone marrow. They also found spike protein in the perinuclear space of meningeal cells and around neurons in the brain cortex.

They identified SARS-coV2 RNA and nucleocapsid protein in about half each of the skull samples and meninges samples.

So, very good evidence that the the virus and viral proteins are getting into human skulls and meninges, but still not evidence that they persist.

 

So far, this is a nicely written paper - it's quite straightforward for such technical things.
From a German team.

Proteomics profiling of COVID-19 patient skull marrow, meninges, and brain samples
They compared the proteins in the skull and brain tissues of 10 Covid-19 patients and 10 non-Covid patients, reporting similar sets of proteins within each group, but less similarities between the groups.

Here's the PCA analysis of the Covid and non-Covid protein sets

When they looked at the proteins that were different in the Covid-19 nonsurvivors' bone marrow, meninges and brain cortex, they found a whole lot associated with a viral infection and immune responses. There is detail there that looks like novel findings, potentially useful for managing acute infections. They do mention NDUFA proteins, noting loss or dysfunction of these problems can impair mitochondrial function, suggesting this might be relevant to the symptom of chronic fatigue.

 

Spike S1 protein triggers proteomics changes in the mouse skull marrow, meninges, and brain
They did similar sorts of things with the mice, looking at proteins in the skull and brain tissues 3 days after the injection of the spike protein or controls. As in the human tissues, they found proteins involved in immune responses, namely NETs formation, neutrophil degranulation and PI3K-AKT pathways. In the mouse brain cortex exposed to the spike protein, they found proteins associated with neurodegeration. NDUFA makes an appearance.

Spike protein from the skull marrow leads to brain cortex neuronal injury
They microinjected the spike protein directly into the mice skull marrow. The spike protein reached the meninges and brain parenchyma within 30 minutes. They found brain cell death and neuronal injury 3 and 28 days after injection.

Spike protein persists in the human skull marrow
Here's the persisting bit.
They looked for spike protein in the skulls of 34 people who died from non-COVID related causes during the pandemic. They found spike protein in 10 of the people. It's inferred that these people were not testing positive to Covid-19 at the time they died.

 

Just as aside, it's a bit sobering to read about a mutation in the Covid virus that makes it infect mice. I'm not sure if that's just a lab thing or if it is out there in wild mice. The virus must be mutating its way through a whole lot of species.

From the discussion: they talk about significant brain tissue loss in mild Covid-19 cases. I'm not sure about the strength of evidence for that.

Do you not find the idea of skull meninges channels connecting the skull marrow to the meninges convincing? Are the channels only vascular, so that there is still a blood brain barrier?

 

It sounds to me as though these channels aren't vascular; a very recent finding
https://news.harvard.edu/gazette/st...s-key-to-detection-of-brain-infection-injury/

 

I think there is often a confusion in research between regulates (controls), and interacts with (affects).