How does SARS-CoV-2 come to mind and destroy the sense of smell?

One of the early indicators of imminent SARS-CoV-2 infection is the sudden and complete loss of odor and taste. Often, these symptoms persist long after the infection appears to have disappeared. How do these viruses invade the nervous system? And why is the olfactory / gustatory system particularly targeted?

In an article posted on the NIH Director’s blog, Francis Collins recently suggests that many neurological symptoms of COVID-19 can be explained by vascular damage associated with widespread inflammation of the body rather than infection of the brain tissue itself. Explains NIH research in Japan. This may be common, but it doesn’t tell us much about why odors are sacrificed so often. In addition, most of the autopsy patients were elderly, had serious comorbidities, and many died “COVID-19” rather than “COVID-19”. In fact, it was not documented whether any of them actually lost their sense of smell.

The director is New research From Experimental Medicine Journal, The authors found some immunohistochemical evidence of SARS-CoV-2 in the brain. In particular, antibodies to peplomer suggest that SARS-CoV-2, or at least some of it, can infect neurons in the cerebral cortex. The authors also found that infection with humanized mice that overexpress human brain organoids and human-type ACE2 receptors can detect viral mRNA via intraneuronal qPCR. cell.. In mice, the virus was introduced either through the intranasal route or by direct injection into the ventricles. Using electron microscopy, they were also able to identify viral particles budding from the host endoplasmic reticulum and record significant cell death.

Other researchers I found it The ACE2 is expressed in supporting cells, stem cells, and perivascular cells, not in neurons.In particular, the so-called persistent cells of the olfactory epithelium, and the pericytes in them. Olfactory bulb It turns out that it has abundant ACE2 itself.The author then concludes non-infectious diseaseNerve cell It is thought to be the cause of anosmia and other disorders in odor perception.

Similarly, other studies using cell culture systems that model the blood-brain barrier have found that SARS peplomers can easily cross this barrier and infect the endothelial cells that line the cerebrovascular system. More generalized nerve infiltration was found in vivo as a result of diffuse inflammation and ischemia secondary to vascular injury. At this time, it is unclear whether the virus can simply germinate cell-to-cell and cross the BBB, or whether all leukocytes are compressed and carry them.

If this is the whole story, why don’t we just lose the brain’s ability to smell and taste, but everything else? The answer is that this is probably not all. More likely, we are dealing with a very unique monster with laser-like precision never seen before in our sensory attacks. I have never witnessed a virus with this particular tendency, but virologists are familiar with many other viruses with specific specificities. For example, both rabies and poliovirus access somatic motor neurons in the spinal cord by first breaking the neuromuscular junction (NMJ) in muscle tissue.

In rabies, nicotinic acetylcholine receptors and neuromuscular adhesion molecules (NCAM) have been identified as the major NMJ receptors for the virus. For polioviruses that can replicate in motor neurons, members of the Ig superfamily known as CD155 have also been identified as axonal receptors. Transneuronal diffusion of these types of viruses into higher regions occurs via various types of retrograde and antegrade directional motor proteins with direct synaptic-to-synaptic transmission. Other evidence is HSV-1, vesicular stomatitis virus (VSV), Borna disease virus (BDV), influenza A virus, parainfluenza virus, rabies, and even prion to CNS via the anterograde olfactory pathway. It suggests that it can be invaded.

Some viruses, such as Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6), overstimulate immune cells in the brain, attacking unique proteins found only in myelinated cells, and finally. It is thought to cause MS-like degeneration. ..For example, myelin-specific CD4 + and CD8 + T cells Recently discovered In both the peripheral and central nervous system of some types of viral encephalitis. In the case of the JC virus, B cells in immunocompromised patients can infiltrate the CNS and transfer the virus to oligodendrocytes and astrocytes, causing a fatal inflammatory disease called progressive multifocal leukoencephalopathy (PML). there is. What clues are now available to understand what SARS is doing in the light of our new understanding of these particular viral tropisms in the nervous system?

One approach is to use existing knowledge of the parallel pathways of olfaction and taste to ask the patient which odor and taste are lost, restored, and in what order. With the exception of the apparent sweet and sour, salty and bitter perceptions, the rest of our taste flow has been found to be mostly post-nasal olfaction. While this system is optimized to detect taste substances inside the mouth during exhalation, our normal sense of smell is optimized to detect external molecules that are inhaled throughout the olfactory epithelium. I will. These primary sensory pathways are complemented by separate chemosensory channels that carry chemically initiated sensations in the touch channels. Mouth sensations such as spicy capsaicinoids and cool peppermint are transmitted via TRPV4 receptors and to the trigeminal nerve.

The important thing here is to find out where these sensations overlap. For example, if coffee and cinnamon are the first things that a recovering patient can detect, where and how exactly is the problem? In other words, do they first sniff it by inhalation through the nose or exhalation through the mouth, and can they taste it when they are not breathing at all? Is it an attractive scent or an unpleasant scent that may tend to return to the beginning? Can I smell and taste peanut butter, skunk, and burning homes? By pooling the answers and looking for commonalities, it may be possible to connect which pathways and higher brain centers are most affected.

In an ongoing search for clues, the next step may be to ask if there are any drugs that may help restore odor or taste, and how these drugs usually work. Hmm. In some cases, combination therapy with dexamethasone and steroids such as theophylline seemed to help restore function. Both seem to be necessary as at least one patient who stopped taking theophylline arm for treatment lost sensation of smell again. Recovered only when theophylline was resumed. For complete olfactory dysfunction with severe olfactory distortion and even hallucinations, the low dose antipsychotic haloperidol provides significant relief.Another latest study is anosmia Effectively improve With steroid fluticasone nasal drops, dysgeusia is overcome with triamcinolone oral paste.

Although some types of neurons have been shown to express low levels of the SARS-Cov-2 peplomer ACE2 receptor, other important proteases or other receptors such as TMPRSS2 and neuropyrin-1 The possibility of cofactor co-expression remains complete. Comparing the invasion mechanisms of other related coronaviruses, or similarly unrelated viruses that infect the brain via the olfactory pathway, may provide more clues. A good example is the OC43 coronavirus, one of the viruses that causes the common cold. OC43 can get Access to the brain Through N-acetyl-9-O-acetylneuraminic acid, it then hijacks axonal transport to reach higher olfactory areas such as the piriform cortex. The latest version of OC43, known as genotype D, was discovered in 2004 and is believed to be due to a recombination event between related genotypes B and C.

As with OC43, some researchers also believe in the new furin cleavage site that is characteristic of SARS-CoV-2. Virus, May have arisen from a recombination event with another event Coronavirus.. However, recombination between more distant classes of coronavirus, including the furin site, may be less likely than intraclass recombination.

© 2021 Science X Network