Few of Covid-19’s peculiarities have piqued as much interest as anosmia, the abrupt loss of smell that has become a well-known hallmark of the disease. This sense is lost in Covid-19 patients even if the nose is not stuffed. It can cause food to taste like cardboard or coffee to smell noxious.
Scientists are now starting to unravel the biological mechanisms that have been a mystery. The neurons that detect odors do not have the receptors that the coronavirus uses for entry, leading to a long debate over whether they can infect cells.
Insights gleaned from new research could shed new light on how the coronavirus might affect other types of brain cells, leading to conditions like “brain fog,” and possibly help explain the biological mechanisms behind long Covid — symptoms that linger for weeks or months after the initial infection.
This new research, in conjunction with previous studies, resolves the question of whether the coronavirus can infect nerve cells that detect odors. The researchers discovered that the virus also attacks other supporting cells in the nasal cavity.
The virus is shed by infected cells and they die. In response, immune cells flood the area to fight it. The inflammation causes damage to smell receptors, proteins that are found on the surface nerve cells of the nose and transmit information about odors.
Researchers reported that the process altered the complex organization of genes in these neurons, effectively short-circuiting them.
Their paper significantly advances our understanding of how viruses affect cells that are critical for the sense of smell, even though they are not directly infected.
“It’s clear that indirectly, if you affect the support cells in the nose, lots of bad things happen,” Dr. Datta said. “The inflammation in the adjacent cells triggers changes in the sensory neurons that prevent them from working properly.”
Indeed, many complications of Covid appear to be caused by the immune system’s friendly fire as it responds to infection by flooding the bloodstream with inflammatory proteins called cytokines, which can damage tissue and organs.
“This might be a general principle: that a lot of what the virus is doing to us is a consequence of its ability to generate inflammation,” Dr. Datta said.
The new study is based upon research at the Zuckerman Institute and Irving Medical Center at Columbia University, New York; New York University Grossman School of Medicine and the Icahn School of Medicine in Mount Sinai in New York; Baylor Genetics Houston; and the School of Medicine of the University of California at Davis. The research was published online by Cell in February.
The scientists examined 23 Covid-infected patients’ human tissue and golden hamsters. Scientists tracked the effects of the original coronavirus on the hamsters over time.
(How can you tell if your golden hamster is losing its sense of smell?) You don’t feed it for several hours and then bury Cocoa Puffs in its bedding, said Benjamin tenOever, a professor of microbiology at NYU Langone Health and an author of the new research. Hamsters that are able to smell the cereal will find it in seconds.
Researchers discovered that the virus did not infect neurons. It only affected cells that support the olfactory system. It was enough to cause a loss in smell by altering the function of nearby neurons.
The Coronavirus Pandemic: Key Information
A new U.S. strategy. The White House unveiled a virus response strategy that aims for a “new normal,” but much of it will need congressional funding. The plan includes a “test to treat” initiative that would provide antiviral medications to patients as soon as they learn they are infected.
The immune response altered the architecture of genes in the neurons, disrupting production of odor receptors, said Marianna Zazhytska, a postdoctoral fellow at the Zuckerman Institute and one of the paper’s first authors, along with a graduate student, Albana Kodra.
“It is not the virus itself causing all this reorganization — it’s the systemic inflammatory response,” Dr. Zazhytska said. “The nerve cells are not hosting the virus, but they are not doing what they did before.”
The ability of the olfactory nerves to send and get messages is affected. But the neurons don’t die, and so the system can recover after the illness resolves.
Earlier work at the Zuckerman Institute showed that neurons that detect smells have complex genomic organizational structures that are essential to the creation of odor receptors, and the receptor genes communicate among themselves very intensively, said Stavros Lomvardas, one of the paper’s corresponding authors.
“We saw early on that upon infection, the genomic organization of these neurons changes completely — they’re unrecognizable compared to how they normally are,” Dr. Lomvardas said.
“There is a signal released from the infected cells that is received by the neurons that normally detect odors, and tells them to reorganize and stop expression of olfactory receptor genes,” he said.
He suggested that this might be an evolutionary adaptation, which offers some form of antiviral protection and whose main purpose could be to stop the virus from entering the brain. “That was a relief for us,” he said. “That was one piece of good news.”
Source: NY Times