The #coronavirus seems to cause damage to the olfactory neurons in the nose, scrambling their nuclei.
Researchers are finally making headway in understanding how the #SARSCoV2 coronavirus causes loss of smell. And a multitude of potential treatments to tackle the condition are undergoing clinical trials, including steroids and blood plasma.
Once a tell-tale sign of COVID-19, smell disruption is becoming less common as the virus evolves. “Our inboxes are not as flooded as they used to be,” says Valentina Parma, a psychologist at the Monell Chemical Senses Center in Philadelphia, Pennsylvania, who helped field desperate inquiries from patients throughout the first two years of the pandemic.
A study published last month1 surveyed 616,318 people in the United States who have had COVID-19. It found that, compared with those who had been infected with the original virus, people who had contracted the Alpha variant — the first variant of concern to arise — were 50% as likely to have chemosensory disruption. This probability fell to 44% for the later Delta variant, and to 17% for the latest variant, Omicron.
But the news is not all good: a significant portion of people infected early in the pandemic still experience chemosensory effects. A 2021 study2 followed 100 people who had had mild cases of COVID-19 and 100 people who repeatedly tested negative. More than a year after their infections, 46% of those who had had COVID-19 still had smell problems; by contrast, just 10% of the control group had developed some smell loss, but for other reasons. Furthermore, 7% of those who had been infected still had total smell loss, or ‘anosmia’, at the end of the year. Given that more than 500 million cases of COVID-19 have been confirmed worldwide, tens of millions of people probably have lingering smell problems.
For these people, help can’t come soon enough. Simple activities such as tasting food or smelling flowers are now “really emotionally distressing”, Parma says.
A clearer picture of how SARS-CoV-2 causes this disruption should help to create better therapies for the condition. Early in the pandemic, a study showed3 that the virus attacks cells in the nose, called sustentacular cells, that provide nutrients and support to odour-sensing neurons.
Since then, clues have emerged about what happens to the olfactory neurons after infection. Researchers including biochemist Stavros Lomvardas at Columbia University in New York City examined people who had died from COVID-19 and found that, although their neurons were intact, they had fewer membrane-embedded receptors for detecting odour molecules than usual4.
This was because the neurons’ nuclei had been scrambled. Normally, the chromosomes in these nuclei are organized into two compartments — a structure that enables the neurons to express specific odour receptors at high levels. But when the team looked at the autopsied neurons, “the nuclear architecture was unrecognizable,” Lomvardas says.
Other studies suggest why only some people experience long-term smell loss. In January, a research team reported5 finding a genetic mutation in people that was associated with a greater propensity for smell or taste loss. The mutation — a change to a single ‘letter’, or base, of DNA — was found in two overlapping genes, called UGT2A1 and UGT2A2. Both encode proteins that remove odour molecules from the nostrils after they have been detected. But it’s not yet clear how SARS-CoV-2 interacts with these genes.
There is also evidence of lasting changes to the brain for people with smell loss. In a study published in March6, 785 people in the United Kingdom had their brains scanned twice. About 400 people became infected with COVID-19 between scans, so the scientists were able to observe structural changes. The COVID-19 survivors showed multiple changes, including markers of tissue damage in areas linked to the brain’s olfactory centre. It’s not clear why this was the case, but one possibility is lack of input. “When we cut off input from the nose, the brain atrophies,” says Danielle Reed, a geneticist also at Monell. “It’s one of the clearest things we know about taste and smell.”
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