Thread by @enn_nafnlaus

Interesting preprint on anosmia / dysosmia associated with SARS-CoV-2

medrxiv.org/content/10.110…

Summary: In SARS-CoV-2 patients, there's dramatic alteration of gene expression in the olfactory bulb of the brain, yet this doesn't correlate with the virus's presence or absence...

... in the olfactory bulb. Seeking to explain this, they checked for a marker of connectivity of sensory nerve fibres (afferants) called OMP-1, and as controls looked at a marker for olfactory lesions (TH) and general. neural activity (SNAP-25)

Results?

OMP-1 - the connectivity marker - was highly depleted in COVID patients (A) with anosmia, in comparison to non-COVID patients. No difference was seen in the marker for lesions (TH) or neural activity (SNAP-25). It thus appears that the pathology is upstream of the olfactory bulb.

While the loss of the sensory nerve connections (deafferentation) was not determined, listed possible measures included "coagulopathy, deleteriously upregulated immune response, autoimmune mechanisms, hypoxia or multiorgan failure"

Good news for the brain? Not exactly.

The problem is that the olfactory bulb is well connected with the amygdala particularly, as well as other brain regions, and the transcriptional changes in it can be seen to a lesser extent in them - alongside as various forms of directly measurable pathology.

In particular, olfactory bulbectomy in rats can be used to stimulate depression. It's also associated with memory and cognitive effects.

One may remember from long ago the first major study that raised concerns of SARS-CoV-2's impact on the brain, based on extensive MRI imaging, showed the most dramatic changes in the olfactory bulb, but next most in well-connected regions.

At the time, the authors suggested direct CNS neuroinvasion via the olfactory nerve. Critics countered that, while rarer, other causes of postviral anosmia can also cause visible neurological changes. The implication being that the observed degeneration is not harmful.

However, as the authors in the current paper note, while the changes are not suggested of direct damage to the olfactory bulb, deafferentation (loss of connectivity) itself can create knock-on effects, not just in the olfactory bulb, but elsewhere in the brain.

Indeed, the loss of the sense of smell is one of the first signs of a number of neurological diseases - most famously, Parkinson's Disease (although one runs into the issue of confounding cause and effect)

parkinson.org/Understanding-…