The study, a collaboration between researchers at Duke, Harvard, and the University of California in San Diego, adds an important insight into a problem that has affected millions of people who have not fully recovered their sense of smell after COVID-19. The findings were published online December 21, 2022, in the journal Science Translational Medicine.
Millions Have Not Fully Recovered Their Sense of Smell After COVID-19
One symptom long associated with COVID-19 infection is loss of smell, says the senior author of the study, Bradley Goldstein, MD, PhD, associate professor in head and neck surgery and communication sciences and neurobiology at the Duke University School of Medicine in Durham, North Carolina.
“Most people who have an altered sense of smell during the acute phase of viral infection will recover smell within the next one to two weeks, but some don’t,” says Dr. Goldstein.
An estimated 15 million COVID-19 survivors around the world have loss of smell that’s continued even after they’ve recovered from the virus, according to a study published in July 2022 in The BMJ.
“One of the driving motivators for our study is that we really don’t have highly specific or effective treatments for these types of smell loss; there’s a real unmet need for developing those kinds of treatments,” Goldstein says.
Researchers Found Inflammation in the Noses of People With Long COVID Smell Loss
By using a biopsy-based approach (taking a small sample of tissue) in the olfactory area of the nose, researchers were able to closely examine the cells of people who have long COVID smell loss versus people who have normal sense of smell, says Goldstein.
Investigators analyzed the olfactory epithelial (the layer of tissue in the nose where smell nerve cells are located) from 24 biopsies, including those from nine patients experiencing long-term smell loss following COVID-19.
The scientists found widespread evidence of T-cells (a type of white blood cell that is an important part of the immune system) as well as inflammation. “We wouldn’t normally expect to see this type of inflammation; it’s almost resembling a sort of autoimmune-like process in the nose,” Goldstein says.
The people who didn’t have long-term smell loss due to COVID-19 had no evidence of the unique inflammation.
Additionally, the researchers found fewer olfactory sensory neurons in the people who had lost their sense of smell, suggesting that the abnormal immune response had destroyed those vital sensory cells in the nose.
Findings May Point the Way to Potential Treatments for Long COVID Loss of Smell
“These findings provide key insights into what might cause long-term smell loss in some people who have long COVID,” says Akiko Iwasaki, PhD, director of the Center for Infection and Immunity at the Yale School of Medicine in New Haven, Connecticut. While Dr. Iwasaki was not involved in this investigation, she is the co-lead investigator of multiple studies on long COVID.
Learning what sites in the nose are damaged and what cell types are involved is a crucial first step toward beginning to design treatments on how to restore smell, says Goldstein. The sensory neurons appeared to maintain some ability to repair even after the long-term abnormal immune response, a sign that researchers found encouraging.
Treatments that reduce this immune response or enhance the repair processes within the noses of these patients could help to at least partially restore a sense of smell, according to the study authors. One treatment option could use creams or sprays to block the inflammation-producing immune cells in the nasal lining, they wrote.
Researchers need to do additional studies in larger numbers of people, says Goldstein. “There are a lot of unanswered questions about what these cells are doing. We need to find out if there are specific drug targets that we can use to try to correct the problem,” he says.
Smell Research May Help Studies on Other Long COVID Symptoms Like Fatigue
Long COVID can affect lots of different organs or systems in the body in different ways, and smell loss is just one of many symptoms, says Goldstein. “We were fortunate that the tissue we were interested in studying — the olfactory lining in the nose — is readily accessible and relatively easy to biopsy,” he says.
This discovery may be useful to researchers who are looking at other long COVID symptoms like fatigue, shortness of breath, and brain fog, symptoms that can’t be studied in the same way as loss of smell.
“Our observations on T-cells and inflammation in the nose could be potentially relevant for understanding what’s going on in those other parts of the body that might be triggered by similar biological mechanisms,” Goldstein says.