How the Coronavirus Steals the Sense of Smell

Few features of Covid-19 have generated as much interest as anosmia, the sudden loss of smell that has become a well-known symptom of the disease. Covid patients lose this feeling even without a stuffy nose; the loss can make food taste like cardboard and the smell of coffee toxic, sometimes lingering after other symptoms have disappeared. Scientists are now beginning to unravel the biological mechanisms that are still a mystery: the neurons that detect odors lack the receptors that the coronavirus uses to enter cells, sparking a long debate about whether they can even be infected.

Findings from new research could shed new light on how 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 persist for weeks or months after exposure. Initial infection.

The new work, along with earlier research, settles the debate about whether the coronavirus infects the nerve cells that detect odors: it doesn’t. But the researchers found that the virus attacks other supporting cells that line the nasal cavity.

Infected cells release the virus and die, while immune cells flood the area to fight the virus. The subsequent inflammation wreaks havoc on olfactory receptors, proteins on the surface of nerve cells in the nose that detect and relay information about odors.

The researchers reported that this process changes the complex organization of the genes in these neurons, essentially shorting them out.

Their work greatly advances the understanding of how the virus affects cells important to smell despite not being directly infected, said Dr. Sandeep Robert Datta, an assistant professor of neuroscience at Harvard Medical School who was not involved in the study.

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

Indeed, many Covid complications appear to be caused by the friendly fire of the immune system as it responds to infection by flooding the bloodstream with inflammatory proteins called cytokines that can damage tissues and organs.

“It could be a general principle that a lot of what the virus does to us is a consequence of its ability to cause inflammation,” Dr. Datta said.

Updated 

March 2, 2022, 6:32 pm ET

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

Scientists examined golden hamsters and human tissue samples from 23 patients who died from Covid. After hamsters were infected with the original coronavirus, scientists tracked 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 cocoa puffs in its bedding, said Benjamin over, professor of microbiology at NYU Langone Health and author of the new study: Hamsters. who can smell will find the flakes in seconds.)

The researchers learned that the virus does not invade neurons but only cells that play a supporting role in the olfactory system. But this was enough to change the function of nearby neurons, resulting in a loss of smell.

Coronavirus pandemic: what you need to know

New US strategy. The White House has unveiled a virus response strategy that aims for a “new normal,” but much of it will require congressional funding. The plan includes a “test for cure” initiative that will provide antivirals to patients as soon as they know they are infected.

Vaccination of adolescents. Five months after immunization, two doses of the Pfizer vaccine appear to offer little or no protection against moderate Omicron disease in adolescents aged 12 to 17, according to new data from the US Centers for Disease Control and Prevention. However, booster shots dramatically increased protection.

The immune response changed the architecture of genes in neurons, disrupting the production of odor receptors, says Marianna Zzarzycka, a research fellow at the Zuckerman Institute and one of the original authors of the paper, along with graduate student Albana Kodra.

“It’s not the virus itself that causes all this reorganization — it’s a systemic inflammatory response,” Dr. Zazhitskaya said. “Nerve cells don’t carry the virus, but they don’t do what they used to do.”

The ability of olfactory receptors to send and receive messages is impaired. But neurons don’t die, so the system can regenerate after recovery.

Earlier work at the Zuckerman Institute showed that the neurons that detect odors have the complex genomic organizational structures that are needed to create odor receptors, and the receptor genes interact very intensely, said Stavros Lomvardas, one of the paper’s authors.

“We have long seen that when infected, the genomic organization of these neurons completely changes – they are unrecognizable compared to how they usually look,” said Dr. Lomvardas.

“There is a signal from the infected cells that are picked up by neurons that normally detect odors and tells them to reorganize and stop expressing olfactory receptor genes,” he said.

He suggested that this could represent an evolutionary adaptation that offers a form of antiviral resistance and whose main goal could be to prevent the virus from entering the brain. “It was a relief for us,” he said. “That was one good news.”