Persistent loss of smell, or anosmia, as experts call it, is one of long covid's strangest symptoms -- and researchers may be one step closer to figuring it out what causes it and how to fix it.
Anosmia has left some covid-19 survivors yearning for the scent of their freshly bathed child or a waft of their once-favorite meal. It's left others inured to the stink of garbage and accidentally drinking spoiled milk.
A small study published online Wednesday in Science Translational Medicine and led by researchers at Duke University, Harvard and the University of California San Diego offers a theory, and new insight, into lingering smell loss.
Scientists analyzed samples of olfactory epithelial tissue, where smell cells live, from 24 biopsies, nine of which were from post-covid patients struggling with persistent loss of smell. Although the sample was small, the results suggest that the sensory deficit is linked to an ongoing immune attack on cells responsible for smell -- which endures even after the virus is gone -- and a decline in the number of olfactory nerve cells.
Bradley Goldstein, associate professor in Duke's Department of Head and Neck Surgery and Communication Sciences and the Department of Neurobiology, an author on the paper, called the results "striking" and said in a statement, "It's almost resembling a sort of autoimmune-like process in the nose."
While there has been research that looks at short-term smell loss and uses animal models, the new study is notable because it focuses on persistent smell loss and uses high-tech molecular analysis on human tissue.
The study reflects enduring interest in the mysterious symptom.
In July, researchers estimated that at least 5.6% of covid-19 patients develop chronic smell problems. That study, published in the peer-reviewed medical trade publication BMJ, also suggested that women as well as those who had more severe initial dysfunction were less likely to recover their sense of smell. Seniors are also especially vulnerable, The Post has reported.
Earlier this month, another small study of covid-19 patients suggested long-term olfactory dysfunction can lead to changes in the brain regions corresponding to smell. A study published in February, which the Duke study builds on, found that individuals who died of covid-19 had fewer membrane-embedded receptors for detecting odor than expected.
Loss of smell can have significant implications. It's a mechanism for threat detection -- from the gas stove you accidentally left on to the stomach-turning smell of a rotten egg. And it's a sense closely associated with memories.
Carol Yan, an otolaryngologist and head and neck surgeon at the University of California at San Diego as well as an author of the new study, has treated patients with persistent smell loss.
"It's quite devastating for them. And a lot of times, at this point, it's been over two years of smell loss," she said. "They're wondering, 'Why me? Why do I still have smell loss compared to so many of my friends, colleagues, family members who have recovered?'"
Doctors have struggled to explain what causes it.
"Clinically, when you look at these patients and you look in their noses, everything looks pristine," she says. "So this is happening on a molecular level."
The study offers some hope, Yan says, because while some have suggested the smell deficit is linked to the central nervous system, this research offers evidence that at least some of the problem is due to inflammation in the nose, where the virus originally attacked. It might mean there is potential for easier, topical treatments.
For Yan, the research about the localized immune response supports other research she's done into platelet-rich plasma as a treatment for smell loss.
"What we found in the clinical trial is actually PRP has a greater likelihood of improving outcomes for covid 19-related smell loss compared to placebo," she says, cautioning that PRP, which has anti-inflammatory qualities, isn't "magic bullet" and needs more in-depth research -- but seems promising.
And the stakes are high. With smell, Yan says, comes your ability to enjoy food and the environment around you. It even affects how you connect with others.
"I've had patients actually come to see me and say 'I'm a little embarrassed to come see you. I didn't think it was a big deal. I just lost my sense of smell, but it's actually impacted my quality of life significantly," she said.