Smell loss, a not so rare COVID-19 complication that we don't understand how it works

"Those who do not know history are obliged to repeat it" This famous phrase that could be from any history teacher to his suspended students has been attributed to great figures in history such as Napoleon or the philosopher George Santayana. In a modern version of it we could say that "those who do not know the consequences of a viral infection are obliged to be amazed by them". We refer in this case to the well-known anosmia that is attributed to COVID-19. When people read the symptoms and the aftermath of the disease, they are amazed,  or not believed that it can cause total or partial loss of smell. However, anosmia or, its moderate version, hyposmia has been found in large numbers of patients.

Image Credit: Harvard Medical School

A meta-analysis carried out with the data provided by countries on all continents has not revealed a clear relationship between infection and loss of the sense of smell. The percentage of those affected with anosmia is very uneven. While in Iran 83% of a small study showed loss of smell, in Iceland only 11.5% of cases showed this symptom. This can be due both to the way in which the loss of smell is measured, as well as the severity from which it is considered that the smell has been lost. The more homogeneous and meticulous the studies have been, the greater the correlation has been found between the disease and the loss of smell. This enormous variability has created some problems in establishing anosmia as a factor to consider for the early detection of COVID-19 cases. Although it is true that anosmia would be an easy and quick way to pre- screen possible positive COVID-19 tests, the tests would have to take into account other factors that decrease the sensitive power of smell, such as age or smoking. In this regard, the American Academy of Otolaryngology-Head and Neck Surgery (AAO -HNS) has created the COVID-19 Anosmia Reporting Tool. A compendium of questions that can be completed online to obtain data to study the effects of COVID-19 on the sense of smell.

Anosmia is a common symptom and sequela of viral infections. The flu or the common cold is common cause of anosmias and also loss of the sense of taste with which smell is closely related. It is easy to understand that a virus that affects the respiratory tract also affects smell, which receives signals in the same pathway. The loss of smell caused by viruses is related to damage done to olfactory receptor neurons.

A recent Italian study has given hope to all those people who cannot smell their morning coffee after passing COVID-19. Nine out of ten of the patients recover their sense of smell completely within a month after recovering from the infection, which is in agreement with the rest of other viral infections studied. To date, total recovery after one year is around 80% of patients.

The autopsy of SARS -CoV-2 patients has revealed neurological damage to the central nervous system. In part this is not surprising since the nervous system relies on the angiotensin-converting enzyme 2 (ACE2), which is the gateway for SARS-CoV-2 into human cells. In this scenario, the infection of the neurons of the medulla oblongata, where the sense of smell is processed, could be related to anosmia. On the other hand, protein expression tests have shown that olfactory sensory neurons located inside the nose do not express ACE2. However, not all cases of anosmia were associated with brain damage. A study published in Science Advences appears to solve this conundrum by targeting support cells, epithelial cells, and blood vessel pericytes. The malfunction of these cells that intervene in inflammatory processes is related to losses in the activity of the neurons to which they support.

The relationship between various effects of COVID-19 and pericytes have already been reported previously in both the lungs and the brain. Pericytes are involved in the maintenance of the blood-brain barrier or between the blood vessels and the lungs. SARS -CoV-2 attacks pericytes, causing the loss of the protection barrier. Consequently, the fluid leaks and pulmonary edema occurs in the case of the lungs. In the case of olfactory neurons and damage to pericytes, two hypotheses are considered. On the one hand, damage to the pericytes of the blood vessels that supply the neurons would induce an inflammatory response that would affect the activity of the neurons. Or, since pericytes are the cells that keep neurons nourished and oxygenated, when these fail, the neurons would see their ability to act reduced due to lack of nutrients.

In summary, anosmia is a common symptom of many viral infections. If its sampling could be standardized and used as an indicator of infection, it could greatly speed up the diagnosis of patients. On the other hand, the mechanisms that cause it are still being studied in COVID-19 and other viral infections. Fortunately, it seems that the effects of the infection on the smell are temporary.

References

Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Science Advances. Jul 2020.
Smell dysfunction: a biomarker for COVID-19 Int Forum Allergy Rhinol . Aug 2020. 
Olfactory dysfunction in the COVID-19 outbreak. J Investig Allergol Clin Immunol. May 2020. 
COVID-19: the vasculature unleashed. Nature Reviews Immunology; volume 20. May 
Https://www.entnet.org/content/reporting-tool-patients-anosmia-related-covid-19

Related Articles

Where to place our bet for COVID-19 treatment, vaccine or monoclonal antibodies?

What will be the first cure for COVID-19?

Antivirals, an arms race in COVID-19 era

Can the experimental drug, remdesivir defeat 2019-nCoV?

Are COVID-19 antibody tests really USELESS?

Are kids at lower risk in COVID-19 pandemic?

COVID-19: when can we call it safe and go back outside?