From the first reports coming out of Wuhan, Iran and later Italy, we
knew that losing your sense of smell (anosmia) was a significant symptom
of the disease. Now, after
months of reports, both anecdotal and more rigorous clinical findings, we think we have a model for how this virus may cause smell loss.
One of the most common
causes of smell loss is a viral infection, such as the common cold, sinus or other upper respiratory tract infections. Those
coronaviruses
that don’t cause deadly diseases, such as COVID-19, SARS and Mers, are
one of the causes of the common cold and have been known to cause
smell loss. In most of these cases,
sense of smell returns when symptoms clear, as smell loss is simply the result of a blocked
nose, which prevents aroma molecules reaching
olfactory receptors in the nose. In some cases, smell loss can persist for months and years.
For the novel coronavirus (SARS-CoV-2), however, the pattern of smell loss is different. Many people with COVID-19 reported a
sudden loss of sense of smell and then a sudden and full return to a normal sense of smell in a week or two.
Interestingly, many of these people said their
nose was clear,
so smell loss cannot be attributed to a blocked nose. For others, smell
loss was prolonged and several weeks later they still had no sense of
smell. Any theory of anosmia in COVID-19 has to account for both of
these patterns.
This sudden return of a normal sense of smell suggests an obstructive
smell loss in which the aroma molecules cannot reach the receptors in
the nose (the same type of loss one gets with a clothes peg on the
nose).
Now that we have
CT scans
of the noses and sinuses of people with COVID-19 smell loss, we can see
that the part of the nose that does the smelling, the olfactory cleft,
is blocked with swollen soft tissue and mucus—known as a cleft syndrome.
The rest of the nose and sinuses look normal and patients have no
problem breathing through their nose.
We know that the way SARS-CoV-2 infects the body is by attaching to
ACE2 receptors on the surface of cells that line the upper respiratory
tract. A protein called TMPRSS2 then helps the virus invade the cell.
Once inside the cell, the virus can replicate, triggering the immune
system’s inflammatory response. This is the starting point for the havoc
and destruction that this virus causes once in the body.
Initially, we thought that the virus might be infecting and
destroying the olfactory neurons. These are the cells that transmit the
signal from the aroma molecule in your nose to the area in the brain
where these signals get interpreted as “smell”.
However, an
international collaboration
showed recently that the ACE2 proteins the virus needs to invade the
cells were not found on the olfactory neurons. But they were found on
cells called “sustentacular cells”, which support the olfactory neurons.
We expect that these support cells are likely to be the ones that are
damaged by the virus, and the immune response would cause swelling of
the area but leave the olfactory neurons intact. When the
immune system has dealt with the
virus,
the swelling subsides and the aroma molecules have a clear route to
their undamaged receptors and the sense of smell returns to normal.
So why does smell not return in some cases? This is more theoretical
but follows from what we know about inflammation in other systems.
Inflammation is the body’s response to damage and results in the release
of chemicals that destroy the tissues involved.
When this inflammation is severe, other nearby cells start to be
damaged or destroyed by this “splash damage”. We believe that accounts
for the second stage, where the olfactory neurons are damaged.
Recovery of smell is much slower because the olfactory neurons need time to regenerate from the supply of stem
cells
within the lining of the nose. Initial recovery is often associated
with distortion of the sense of smell known as parosmia, where things
don’t smell like they used to. For many parosmics, for instance, the
smell of coffee is often described as burnt, chemical, dirty and
reminiscent of sewage.
Physiotherapy for the nose
Olfaction has been called the
Cinderella of the senses
because of its neglect by scientific research. But it has come to the
forefront in this pandemic. The silver lining is that we will learn a
lot about how viruses are involved in smell loss from this. But what
hope is there for people with a loss of smell now?
The good news is that the olfactory neurons can
regenerate.
They’re regrowing in almost all of us, all of the time. We can harness
that regeneration and guide it with “physiotherapy for the nose”:
smell training.
There is
solid evidence
that many forms of smell loss are helped by this repeated, mindful
exposure to a fixed set of odorants every day and no reason to think it
won’t work in COVID-19
smell loss.
https://medicalxpress.com/news/2020-06-coronavirus-scientists-uncover-people.html
