Covid-19 and the brain

Covid MRI brainA common symptom of Covid-19 is anosmia (loss of the ability to smell) which suggested to some that the virus could get into the brain. More recent evidence seems to bear this out, although there is still a lot of speculation.

I once attended a lecture by Martin Rees, the UK’s Astronomer Royal, who astonished the audience by saying astronomy was a simple subject. He qualified his statement by explaining astronomy is simple compared to biological science particularly, biochemistry. We may be able to figure out the beginnings of the Universe, we may be able to count the stars it contains and we may be able to figure out its end. But we are unlikely to figure out but a fraction of the billions, or trillions of different molecules and their interactions going on in the human body. And within all that complexity, the brain stands supreme. The chemical and cellular interactions within that squidgy ball are… well, mind blowing.

All that complexity makes the brain vulnerable, and it doesn’t take much to upset its function. It’s not surprising therefore that the brain has evolved some special methods of protecting itself, and above all, that task falls upon the blood-brain-barrier. The blood-brain-barrier exists is a construction of cells and proteins along the walls of a network of blood vessels surrounding the brain. There are a variety of specialised cells in the blood-brain-barrier, including, amongst others, endothelial cells and astrocytes. Endothelial cells, or to be more precise in the blood-brain-barrier’s case, cerebral vascular endothelial cells, are associated with what we know as tight junctions, which are unusual in the biological sciences because their name actually describes them in plain language. Astrocytes help maintain tight junctions by secreting substances which regulate their properties – opening them up to some substances, like nutrients, while keeping others, like toxins, out. This combination of cell types and tight junctions is something akin to an Anglo-Saxon shield wall, able to let friends pass while also repelling the enemy. On the whole, the shield wall of the blood-brain-barrier prevents undesirables from getting through, but like the Anglo-Saxons found out at the battle of Hastings, things can go very wrong.

There are questions about whether its SARS-CoV-2 (the causative virus for Covid-19) that gets into the brain or whether it’s the virus’s spike protein (known as S1 protein). Some viruses can get into the brain – perhaps Rabies lyssavirus (rabies) being the most notorious. Of course SARS-CoV-2 is nowhere near as deadly as rabies but sometimes, besides anosmia, Covid-19 has been known to cause memory loss, loss of cognition and even strokes. SARS-CoV-2 is an enigmatic virus and there’s still much we don’t know, including how it, or the spike protein, defeats the blood-brain-barrier. From animal models, it appears to attack astrocytes directly, triggering an immune response, leading to an increase in circulating pro-inflammatory cytokines, known as cytokine storm syndrome. It’s this cytokine storm that then potentially leads to brain damage. The immune system, in this case, goes off the tracks (something anti-vaxxers seem to miss when they claim “they have an immune system”. That’s like vowing never to use a bus because I have a car, and assuming the car will never breakdown). MRI scans have shown damage to grey matter, but the images show little consistency from patient to patient, something as yet not understood. Once again, SARS-CoV-2 proves enigmatic.

Serious neurological problems with Covid-19 are thankfully rare, but we shouldn’t be complacent about a virus where we still have so much to learn. Medical science is well aware of lasting effects, known as long Covid, in some patients, although the cause remains elusive. It’s possible the effects in the brain are the cause, but other effects may also be implicated – currently we just don’t know. The picture is also ever changing as new variants emerge. Some think we have finished with Covid, but it’s unlikely SARS-CoV-2 has finished with us yet – it may still hold a few surprises.

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