What the first Italian researchers who studied the loss of smell due to Covid-19 discovered

Researchers Paolo Boscolo Rizzo and Giancarlo Tirelli were among the first in Italy to investigate the odor and taste disorders connected to Covid-19. A line of research which is now in full swing and which will be discussed at Trieste Next

(photo: Andia / Universal Images Group via Getty Images) An almost forgotten sense, overshadowed by all the others even inside of the clinical world, so much so that the techniques to study it or to take care of it can be counted on the fingertips. Before the pandemic, the sense of smell was just that, so much so that while we would never dream of defining a blind or deaf person without having subjected them to biometric tests, in the case of smell, the majority of investigations have always been based only on patients' reports. and little more. Until the Covid-19 pandemic, when sensory disturbances affecting smell - and also taste - reminded us how much this nuance of our sensoriality is very important for health.

We discussed this with Paolo Boscolo Rizzo, professor of otolaryngology at the University of Trieste. Under the guidance of Professor Giancarlo Tirelli, director of the Clinic of the University of Trieste, the researcher was among the first in Italy to shed light on the loss of smell and taste in patients with Covid-19 and will be present in Trieste Next , scientific research festival scheduled from Friday 24 to Sunday 26 September in the meeting Geni e Senses: a world yet to be explored together with the interactive laboratory We measure and color the sense of smell in collaboration with the Higher School of Advanced Studies (Sissa) of Trieste .

Direct from the first wave

"In March 2020 there was still no scientific publication on the smell and taste alterations linked to the Sars-CoV-2 infection - he tells Wired Boscolo Rizzo -. There had been rumors, mostly from Korea, of healed people complaining of these ailments, but still nothing academic. As the wave progressed, we therefore decided to investigate ". Thus began, from scratch, a project that would soon involve almost 300 candidates, people who tested positive for the swab, which through a questionnaire revealed that 64% of patients complained of these disorders during the acute phase of the disease. Many of them reported a total loss of the sense of smell. "A striking fact, considering that in no other respiratory infection are these symptoms observed with such frequency", explains the professor.

Follow-up

One of the strategies implemented by researchers from the Trieste clinic, was re-contacted patients on a regular basis even after recovery. "Three months after the onset of symptoms, 25% of them still complained of alterations in smell and taste - explains Boscolo Rizzo - and little changed after six months". After a year, with a figure settling on 20%, the disorder was configured (second only to asthenia) as one of the most frequent symptoms of long Covid, the syndrome characterized by the persistence of one or more signs of the acute phase after some time.

"We did not rely only on the symptoms reported by patients, but also on psychophysical tests conducted in the laboratory and compared with a group of people who had never developed the infection - it goes on scholar -. The tests not only confirmed the disorder, but revealed that it was even more frequent ”. These are tests during which patients are exposed to different odorous substances and with different intensity and which return a more precise measure of the ability to distinguish and perceive odors.

"Since after Covid-19 patients reported Frequent alterations also to the taste, we also carried out an evaluation both of the taste itself and of the postnasal smell, the latter using powders introduced by mouth without taste but which release odorous molecules - says Boscolo Rizzo -. These further tests made it possible to observe that about half of the patients who reported an alteration of taste actually had an alteration of the postnasal smell, very important for the perception of the taste of food ".

Why me?

A further investigation concerns the reasons why many but not all people who have experienced the infection have problems with the sense of smell, not only anosmia (loss of the ability to perceive odors), but also parosmia (distortion of olfactory perception) and phantosmia (ie to smell of substances that are not there). What is at the origin of this difference? The evidence collected during the first wave indicated that patients with the most severe symptoms tended to complain less alterations in the sense of smell and taste and that people with more moderate symptoms were the most prone to these disorders, so much so that there was also the hypothesis that we were faced with two different types of infections, one affecting the lower respiratory tract and one affecting the upper respiratory tract, with different symptoms.

"Today, thanks to studies conducted on inflammation, we know that the The picture of severe infection is not associated with a lower risk of having alterations in the sense of smell and the hypothesis on the reasons for the prevalence of this symptom is clearer ”, explains Boscolo Rizzo. On the one hand, it could concern the host, that is us, due to polymorphisms of the Ace2 receptor gene to which the virus binds and which make us more or less susceptible.

Another possibility are the differences between the variants , on the chronology of which all the research on the front must be "calibrated". "It seems that the original strain, the one that caused the epidemic in China, rarely gave alterations to taste and smell, unlike the one with which the epidemic took hold in Italy - continues the professor -. A difference due, perhaps, to the replacement of a nucleotide in the gene that codes for the spike protein. Now with the delta variant there seems to be a lower frequency in the alterations, but it is a side where there is still a lot to investigate ".

Recovering the sense of smell: the possibilities

One of the most accredited hypotheses on the mechanism by which Sars-CoV-2 alters sense of smell and taste is that the virus, once deep in the nasal cavities , affects the support cells of the olfactory epithelium, those that take care of the neurons responsible for picking up the volatile molecules and in direct connection with the centers of the brain where the odor sensation is processed. These are cells - unlike neuronal ones - very rich in Ace2 receptors, target of the spike protein of the virus, and it is probable that once they are "hooked" by the pathogen their nutritional effect on the neurons is lost, which are then damaged afterwards. .

"Fortunately, precisely because these neurons are the only ones in direct contact with the external environment and are somehow 'accustomed' to being damaged, they are endowed with regenerative potential, that is, we can stimulate them to try to recover the lost meaning ”, explains Boscolo Rizzo. What the researchers of the Trieste clinic are carrying out in this direction is the olfactory training, already present in the literature in the treatment of other forms of anosmia of viral origin and for which there is also evidence in the case of Covid-19. “The patient is invited to expose himself for 12 weeks, twice a day, to a series of essences such as rose, lemon, eucalyptus and cloves, to stimulate the regeneration of olfactory neurons - explains the researcher -. There are people who have spent a year completely devoid of smell and who begin to improve after training ".

On the pharmacological front, however, for now the only option supported by evidence," but which should be taken into consideration consideration in the initial phase of the disease or in the case of evidence of inflammatory processes in the region of the olfactory epithelium ", adds the scientist, is the treatment with corticosteroids.

The next steps

The the effectiveness of the olfactory training will have to be confirmed on a large scale: that is, the candidates will have to repeat the psychophysical tests after some time. The monitoring of Covid-19 patients with olfactory disorders will last for at least three years, "this is because the investigations conducted on other respiratory viruses suggest that recovery can also occur very slowly, and only at that point will we perhaps have the real percentage of patients who suffered irreversible damage ", explains Boscolo Rizzo.

Scientists are also subjecting patients with more important conditions to magnetic resonance imaging, which in some cases has shown true atrophy of the brain areas normally responsible for processing the olfactory signals, in order to understand if there are more probabilities of a persistence of the symptom. "Further open fronts", concludes the professor, "concern electrophysiological aspects and evaluation of the damage to the neuroepithelium with the aim of identifying the molecular alterations caused by this infection, on which we are working together with the group of Professor Anna Menini , head of the Sissa interdisciplinary neurobiology laboratory ".


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Coronavirus Long Covid Neuroscience Health Variants Sars-Cov-2 globalData.fldTopic = "Coronavirus, Long Covid, Neuroscience, Health, Sars-Cov-2 Variants "

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