A common symptom of the SARS-CoV-2 virus - pictured in this electron microscope image - is the loss of smell. Photo / NIAID-RML
A common symptom of the SARS-CoV-2 virus - pictured in this electron microscope image - is the loss of smell. Photo / NIAID-RML
It happens to more than eight in 10 Covid-19 patients - yet scientists still don't have a firm explanation why the coronavirus knocks out peoples' sense of smell.
Now, a team of researchers including a University of Auckland neuroscientist are shedding more light on that tell-tale symptom, while also raisingsome concerning potential long-term neurological effects of Covid-19.
In a project with collaborators at the US National Institutes of Health (NIH), Dr Helen Murray has been poring over scans of brain tissue taken from 19 US patients who died within hours to months of reporting symptoms.
While Covid-19 is primarily a respiratory disease, it's been estimated that a third of hospitalised patients have neurological symptoms.
The most common are dizziness and headache but stroke may occur in as many as five per cent of hospitalised cases, initial studies suggest.
"The most common severe neurological effects, stroke and encephalitis, can have life-changing implications, especially for someone who is young and was previously healthy," said Murray, a research fellow at the university-based Centre for Brain Research.
She became involved in the programme because of her expertise with the olfactory bulb - the tiny part of the brain that enables us to smell.
It's also the only part of the brain connected - via the nose - to the outside world, making it vulnerable to pollutants and viruses.
In the US, NIH scientists used sensitive magnetic resonance imaging (MRI) machines to reveal signs of bleeding in the deceased patients' brain stems and olfactory bulbs - two regions known for Covid-19 effects.
To gain a closer look, the team added fluorescent antibodies to the brain tissue and tracked them with microscopes.
These antibodies ultimately showed where blood vessels were thinner than normal, and where blood proteins had managed to leak into brain tissue.
Surrounding these leaks were immune cells, which indicated an inflammatory response.
This image shows the difference in brain tissue between patients with and without Covid-19. Blood vessels are green-blue, microglia (immune cells) are magenta and the blood protein fibrinogen is yellow. In the brain tissue of a Covid-19 patient, the fibrinogen has leaked out of the blood vessels and the extra microglia indicate an immune response. Image / Supplied
This type of damage was typically associated with stroke and neuroinflammatory diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis.
"It was striking," said Murray, who helped examine the scans from Auckland.
"I've looked at tissue from Alzheimer's patients for years now, but I have never seen changes as severe as these in the olfactory bulb."
Scientists have hypothesised that loss of smell commonly accompanying Covid-19 infections could be caused by the SARS-CoV-2 getting into the olfactory bulb.
But in their analysis, Murray and her colleagues saw no such sign of an attack.
Instead, the brain effects they observed appeared to have been part of a broader inflammatory response.
Could these changes have knocked out smell at the same time?
Dr Helen Murray, a Health Education Trust post-doctoral research fellow at the University of Auckland, works with the US National Institute of Neurological Disorders and Stroke. Photo / Supplied
"It's possible," Murray said.
"I would be very surprised if there wasn't an effect, but we still don't know."
A recent Harvard Medical School study focused on a different factor that could sabotage smell: the infection by the virus of cells in the nose that support odour-detecting neurons.
"I think it's very likely that the sudden loss of smell could come from those cells being affected," she said.
"What our work shows is there could also be some downstream effects happening in the brain.
"We can't say for sure that what we observed in the bulbs is causing loss of smell, but it's probably contributing."
Murray said there was still so much more to learn – including the intriguing possibility that Covid-19 patients could have a heightened risk of later developing Parkinson's, Alzheimer's or multiple sclerosis, or suffering stroke.
She noted the Spanish flu pandemic of 1918 was followed by a surge in Parkinson's-like cases - and the world's current total of 115 million Covid-19 infections pointed to the potential scale of any knock-on effects this time.
"This work has really helped us understand what happens to our sense of smell during an infection - and how it can repair itself.
"It's actually one of the few times we've been able to see the effect of an infection on post-mortem tissue in this part of the brain, because usually, people don't pass away from such viruses."
