By Claudio López Bruzual, MD
Taste and smell are two of the most complex sensory systems that human beings possess. Their function is not limited to mere physiology, but they are so intimately linked to memory that they are able to evoke sensations and memories.
As we know, this is possible thanks to the phylogenetic connections the olfactory system has with the paleocortex, and with certain areas of the limbic system. This allows axons to communicate with different brain structures, including the olfactory cortex. In short, brain activity plays an important role in taste and smell, thus, the pathologies that afflict him first can affect these senses.
In fact, long before doctors and researchers realized the havoc the COVID-19 virus provokes, several studies had already pointed to a possible link between loss of smell and neurodegenerative diseases. In this article we will touch on some aspects of the neurological damage that the coronavirus causes in the sense of taste and smell of patients.
A very complex virus
At the beginning of the pandemic, COVID-19 was believed to be just a respiratory disease. But over time, the researchers discovered that in addition to affecting the heart it also damages the brain. The virus is so complex that one of the symptoms that allowed to discover the phenomenon of the so-called asymptomatic patients was precisely the loss of taste and smell.
Reviews and meta-analyses of the literature on the neurological aspects of COVID-19 point to two types of neurological involvement (para and post infectious sequelae), as well as three main pathogenic mechanisms of the Central Nervous System (CNS) involvement that may have some overlap:
1 Direct primary damage to the CNS parenchyma, which is a rare occurrence.
2 Hyper inflammatory response syndrome (cytokine release syndrome, commonly called "cytokine storm")which has been observed mostly in severe forms of COVID-19. It must be said that this mechanism wasexaggerated during the first months of the pandemic, statistically, it is not a frequent occurrence (Mudd et al., 2020).
3 Systemic sepsis, which can evolve into complications, such as viral encephalitis, and death.
As we said, neurological involvement in COVID-19 patients has been described since the early stages of the epidemic: of 214 patients with COVID-19, 36.4% had neurological symptoms (Mao et al., 2020). A similar study found that 36% of patients reported CNS symptoms (altered consciousness) and peripheral symptoms (e.g., paresthesiaor abnormal tingling and burning) (Wu et al., 2020). A larger study (1099 patients) described other neurological manifestations as myalgias (muscle pain)(14.9%), and headache (13.6%) (Guan et al., 2020).
It has been shown that the type of neurological manifestations in COVID-19 patients is associated with the severity of the disease; strokes, seizures, ataxia (lack of muscle control), disorders of consciousness, and myopathies (muscle diseases) most often occur in severe forms (45.5%) than in less severe (30.2%) (Mao et al., 2020). In several cases, those neurological complications were life-threatening (Carod-Artal, 2020).
Studying anosmia and dysgeusia
On the other hand, loss of smell (anosmia), and altered taste (dysgeusia) are symptoms in the course of the infection. These alterationswere not described in the first reports, evidently, because little was known about the virus at the beginning of the pandemic. In fact,they were initially notified by otolaryngologists (Lüers et al., 2020).
A distinctive feature of dysosmias in COVID-19 is that they appear relatively early, in contrast to what was observed in SARS (Severe Acute Respiratory Syndrome). A second characteristic is that they are rarely accompanied by rhinorrhea.
Hyposmia (reduced olfactory capacity)was one of the first reported dysosmias (distortions of olfactory perception) among COVID-19 patients in Wuhan, China (Mao et al., 2020). On the other hand, of 10,069 patients studied in Tehran (Iran), 48.2% had anosmia or hyposmia, with an abrupt installation of anosmia in 76% of the cases. 83.4% of those patients also exhibited dysgeusia (Bagheri et al., 2020).
Olfactory and gustatory disorders were also registered at 34% of COVID-19 patients in Milan, Italy (Giacomelli et al, 2020). A telephone survey in Treviso and Belluno provinces (Italy) analyzed 202 people who tested positive for SARS-CoV-2. 64% of the subjects reported dysosmias or dysgeusias (more frequently among female patients) which appeared earlier than other symptoms in 12% of cases (Spinato et al, 2020). Furthermore, in Munich, Germany, in a study of 9 patients, 4 had hyposmia, anosmia, dysgeusia or ageusia (loss of sense of taste) (W€olfel et al., 2020). In addition, a joint psychophysical study conducted on COVID-19 patients (in 12 hospitals across Europe) showed a very high incidence (close to 76%) of these symptoms and established correlations between olfactory and gustatory dysfunctions. In fact, dysosmias occurred before dysgeusias (Lechien et al, 2020).
As the pandemic passed the 6-month mark, anosmia and hyposmia appeared more frequently in asymptomatic people (Boscolo-Rizzo et al., 2020), slightly symptomatic (Spinato et al., 2020; Lechien et al, 2020), or these dysfunctions of the olfactory system were the first symptom (Boscolo-Rizzo et al., 2020; Lee et al., 2020a; Gautier and Ravussin, 2020). In many cases, they were the only hint that the patient had been infected with coronavirus (Hjelmesæth and Skaare, 2020).
A statistical study performed in Tehran subjected 60 confirmed COVID-19 patients, and 60 control individuals (distributed in pairs) to the University of Pennsylvania Smell Identification Test (UPSIT). Virtually all patients with COVID-19 (98%) tested positive for dysosmia (Moein et al., 2020):
- Anosmia (olfactory disability) (25%)
- Severe microsmia (decrease in smell) (33%)
- Moderate microsmia (27%)
- Mild microsmia (13%)
- There was only one normosmic patient (normal olfactory capacity) (2%)
60% of participants reported a loss of smell and taste, therefore, the authors of the study suggest that these symptoms are a strong predictor of COVID-19 in untested individuals (Menni et al., 2020). In other tests, it was found a statistically significant correlation between decreased interleukin-6 and the recovery of smell after the episode of olfactory dysfunction (Cazzolla et al., 2020).Smell tests are available for olfactory memory dysfunctions (see, e.g., Frank and Murphy, 2020) and are likely to be used more frequently to assess the degree of loss of the sense of smell and its recovery in patients affected by COVID-19.
A long road ahead
Much remains to be understood and studied about the multiple harmful effects of coronavirus on the brain, lungs, heart, and olfactory system. So far it has been found that some supporting cells, such as sustentacular cells, can get infected with coronavirus, which can cause collateral damage, including the death of olfactory neurons (D.H. Brann, et al). Therefore, it is believed that one of the causes of anosmia (especially the more severe types) is that SARS-COV-2 causes collateral damage to the olfactory neurones.
However, in the absence of conclusive results, there are still many other theories to be proven, such as whether interleuchin-6, CXL-10, and TNF-α, which are present during the cytokine storm, can damage the olfactory nerves (A.P. Cazzolla, et al).
This is one of those cases where the phrase "time will bring the answers" is totally accurate.
