Why Covid causes loss of smell

Few of the quirks of Covid-19 have sparked as much interest as anosmia, the sudden loss of sense of smell, which has become a hallmark of the disease.

Patients with Covid lose this sense even without having a “clogged” nose; loss can make food taste like cardboard and coffee a repulsive odor, occasionally persisting after other symptoms have resolved.

Scientists are now beginning to unravel the biological mechanisms, which have been a mystery: neurons that detect odors lack the receptors that the coronavirus uses to enter cells, which has sparked a long-running debate over whether they can be infected.

Information gleaned from new research could shed light on how the coronavirus can affect other types of brain cells, leading to conditions like “brain fog,” and possibly help explain the biological mechanisms behind long-term Covid – symptoms that linger for weeks or months afterward. the initial infection.

The new work, along with previous studies, ends the debate over whether the coronavirus infects the nerve cells that detect odors: no. But the researchers found that the virus attacks other support cells that line the nasal cavity.

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

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

The paper makes significant progress in understanding how cells critical for smell are affected by the virus despite the fact that they are not directly infected, said Dr Sandeep Robert Datta, an associate professor of neurobiology at Harvard Medical School, who has not participated in the study.

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

In fact, many complications of Covid 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: a lot of what the virus is doing to us is a consequence of its ability to generate inflammation,” Datta said.

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

Scientists examined golden hamsters and human tissue samples from 23 patients who succumbed to Covid. After the hamsters were infected with the original coronavirus, scientists tracked the damage to their olfactory systems over time.

(How do you know a golden hamster has lost its sense of smell? You don’t feed it for several hours and then bury chocolate cereal in its bed, said Benjamin tenOever, a professor of microbiology at New York University and author of the new research. can smell it will find the candy in seconds.)

The virus did not invade neurons, the researchers found, only cells that play supporting roles in the olfactory system. But it was enough to alter the function of nearby neurons, leading to the loss of smell.

The immune response modified the genetic architecture of neurons, disrupting the production of odor receptors, said Marianna Zazhytska, a postdoctoral fellow at the Zuckerman Institute and one of the first authors of the paper, along with a graduate student, Albana Kodra.

“It’s not the virus itself that causes all this rearrangement, it’s the systemic inflammatory response,” Zazhytska said. “The nerve cells are not hosting the virus, but they are not doing what they used to do.”

The ability of olfactory receptors to send and receive messages is disrupted. But neurons do not die and therefore the system can recover after the disease resolves.

Previous work from the Zuckerman Institute has shown that neurons that detect odors have complex genomic organizational structures that are essential for creating odor receptors, and receptor genes communicate with each other very intensely, said Stavros Lomvardas, one of the corresponding authors. of the article.

“We saw early on that, after infection, the genomic organization of these neurons completely changes — they are unrecognizable compared to what they normally are,” said Lomvardas.

“There is a signal released by infected cells that is received by neurons that normally detect odors and tells them to reorganize and stop the expression of olfactory receptor genes,” he said.
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The scientist suggested that this may represent an evolutionary adaptation that offers a form of antiviral resistance and whose main objective is perhaps to prevent the virus from entering the brain. “That was a relief for us,” he said. “It was good news.”

_{Translated by Luiz Roberto M. Gonçalves.}