This is how the coronavirus steals the sense of smell

Few peculiarities of COVID-19 have drawn as much interest as anosmia, the sudden loss of smell that has become a well-known feature of the disease. COVID-19 patients lose this sense even without a stuffy nose; the leak can make food taste like cardboard and coffee smell unpleasant, and can sometimes persist after other symptoms have been overcome.

Scientists are beginning to unravel the biological mechanisms, which have long been a mystery: Neurons that detect odors lack the receptors that the coronavirus uses to enter cells, sparking widespread debate about whether they can become infected.

The results of the new research could shed light on how the coronavirus can affect other types of neurons, giving rise to disorders such as “brain fog””, and perhaps help explain the biological mechanisms underlying prolonged COVID-19, that is, symptoms that persist for weeks or months after initial contagion.

The new research, along with earlier studies, settles the debate about whether coronavirus infects nerve cells that detect odors: It is not like this; however, the researchers found that the virus does attack other supporting cells that line the nasal cavity.

Infected cells shed the virus and die, while immune cells flood the region to fight the virus. The ensuing inflammation wreaks havoc on olfactory receptors, proteins on the surface of nerve cells in the nose that detect and transmit information about odors.

The process disrupts the sophisticated organization of genes in those neurons, essentially short-circuiting them, the researchers reported.

Their work represents a major advance in understanding how cells essential to the sense of smell are affected by the virus, even though they are not directly infected, said Sandeep Robert Datta, associate professor of neurobiology in the School of Harvard Medicine, who was not involved in the study.

“Clearly, indirectly, if you affect the supporting cells of the nose, a lot of bad things happen,” Datta said. “Inflammation in adjacent cells triggers changes in sensory neurons that prevent them from functioning properly.”

In fact, many complications of COVID-19 appear to be caused by the friendly fire of the immune system, which responds to infection by flooding the bloodstream with inflammatory proteins called cytokines, which can damage tissues and organs.

“This could be a general principle: that much of what the virus does to us is a consequence of its ability to cause inflammationDatta commented.

The new study is based on research conducted at the Zuckerman Institute and Columbia University Irving Medical Center in New York; New York University Grossman School of Medicine; the Icahn School of Medicine at Mount Sinai in New York; Baylor Genetics in Houston; and the University of California, Davis School of Medicine. The research was published online in the journal Cell in early February.

The scientists examined golden hamsters and human tissue samples from 23 patients who died of COVID-19. After infecting hamsters with the original coronavirus, the scientists recorded the damage to their olfactory systems over time.

(How do you know a golden hamster has lost its sense of smell? It’s not fed for several hours, and then chocolate cereal balls are buried in where it sleeps, explained Benjamin tenOever, a professor of microbiology at NYU Langone Health and an author of new research. Hamsters that can smell will find the cereal in seconds).

The researchers found that the virus did not invade neurons, but only cells that perform supportive functions in the olfactory systembut it was enough to impair the function of nearby neurons, leading to a loss of smell.

The immune response altered the structure of genes in neurons, disrupting the production of odorant receptors, said Marianna Zazhytska, a postdoctoral fellow at the Zuckerman Institute and one of the paper’s first authors, along with graduate student Albana Kodra.

“It’s not the virus that’s causing all this rearrangement, it’s the systemic inflammatory response,” Zazhytska said. “The neurons don’t harbor the virus, but they don’t do what they used to do.”

The ability of the olfactory receptors to send and receive messages is altered, but the neurons do not die, so the system can recover once the disease is overcome.

Previous research from the Zuckerman Institute has shown that odor-detecting neurons have complex genomic organizational structures that are essential for the creation of odor receptors, and the receptor genes communicate with each other very strongly, said Stavros Lomvardas, one of the authors of the investigation.

“Early on we saw that, after infection, the genomic organization of these neurons completely changes: they are unrecognizable compared to how they usually are,” Lomvardas said.

“Infected cells release a signal that is received by neurons that normally detect odors, and tells them to reorganize and stop the expression of genes for olfactory receptors,” he said.

Lomvardas suggested that this could represent an evolutionary adaptation that offers a kind of antiviral resistance and whose main purpose may be to prevent the virus from entering the brain. “That was a relief for us,” he said. “It was good news.” (I)