Bankova Works to Unravel the Mysteries of Post-COVID Anosmia
When Lora Bankova, MD, a physician-scientist in the Division of Allergy and Clinical Immunology at Brigham and Women’s Hospital, started her research at the Brigham, she didn’t expect to one day be leading a clinical trial to investigate one of the most well-known, but least understood symptoms of COVID-19, anosmia. Anosmia is a phenomenon reported by patients during and in some cases after SARS-CoV-2 infection, defined by a diminished or total loss of the ability to smell and taste, sometimes persisting for months or years.
Lora Bankova
Previous research has indicated that about 60 percent of patients infected with SARS-CoV-2, the virus associated with COVID-19, experience varying degrees of taste or smell loss. Although most recover with time, roughly 2-4 percent of patients don’t fully gain their ability to smell back within six months, accounting for up to 4 million people in the U.S. Our sense of smell is intrinsically linked to our ability to taste and enjoy food. Without it, patients may struggle to enjoy eating, impacting their health, social lives, and overall happiness.
“In the early days of COVID, this condition was poorly defined, and a lot of patients were struggling with the fact that they would go to the physician and describe what they were experiencing, but they didn’t fit into any of the categories of long COVID,” Bankova explained. “They didn’t have pain, they didn’t have rashes, they didn’t have respiratory symptoms, they didn’t have gastrointestinal symptoms. All they had is reduced or distorted sense of smell and taste, so they’re not considered sick people.”
Leading her research team at the Brigham, Bankova hopes to help these post-COVID patients regain their ability to smell by uncovering the complex questions of anosmia.
Shifting Focus in the Pandemic
Bankova was researching tuft cells before the pandemic struck. Tuft cells are a rare type of epithelial cell found in the respiratory and digestive systems of the body that can recognize allergens and damage in the airways. Found in higher concentrations in the olfactory epithelium, Bankova studied olfactory mucosa using pre-clinical models, but dreamed of being able to work closer with humans. As her work began to ramp up, the research ran into an unexpected roadblock: the shutdown due to the COVID-19 pandemic.
She remembers, “We were tinkering with a large data set that arrived literally the day of the shutdown.”
While that might have seemed like a disruption at the time, it ended up being a perfect opportunity.
Bankova had developed an interest in the intricacies of the nose. As part of an allergy and immunology clinic where people came in with nasal problems, patients were seeking care for unique and mysterious symptoms of smell loss. A new avenue for her research was right at her doorstep.
She credits her clinical sciences director, Tanya Laidlaw, MD, director of translational research in the Division of Allergy and Clinical Immunology, for encouraging her to explore a new direction in her research.
She recalls Laidlaw saying, “You know, you’ve always wanted to have a human problem that you’re studying. Here’s a human problem. Why don’t you do that?”
The Impact of Public Support
In the early days of her research, Bankova planned a limited mechanical study comparing nasal mucosa samples of people experiencing anosmia, people who had never had COVID-19, against samples from people who had lost their sense of smell due to chronic rhinosinusitis, a long-lasting condition that causes the sinuses to become swollen and impact a patient’s ability to smell.
While on a ski vacation, Bankova was notified that her study had been approved and that CBS wanted to interview her to learn more about it. Her first, big national interview was a resounding success, creating significant interest in the research.
“All of a sudden, we had so much interest,” she said. “We had hundreds of emails coming our way after the interview, which we were not prepared for, and everybody wanted to contribute because of the urgency of COVID at that time.”
Bankova’s study filled a niche that patients desperately needed. Although they weren’t considered chronically sick in the sense that their health was at risk, “they couldn’t smell and didn’t feel like their experiences were being validated in the clinic.”
With the new support, Bankova launched a registry study that involved interviewing patients with anosmia over a two-year period. “Through the conversations with some of these patients, we developed a questionnaire of their daily experiences,” she said. In it, the team measured the patient’s symptoms, other medical conditions and treatments they tried.
Collaboration has been essential throughout this study. Bankova credits Stella Lee, MD, Rachel Roditi, MD, Regan Bergmark, MD, MPH, and Alice Maxfield, MD, members of the Division of Otolaryngology-Head and Neck Surgery, and Nathaniel Treister, DMD, faculty in the Division of Oral Medicine and Dentistry, who have helped refer patients to the study and are involved in a critical part in the collection of samples from the olfactory and oral mucosa. A collaboration with Adam Haber, PhD, a computational biologist at the Harvard School of Public Health, has helped unearth new signatures in the olfactory and nasal mucosa samples.
Most important to the project, though, are the “boots on the ground” in the Bankova Lab: Dante Minichetti, who leads the recruitment and sample collection efforts, and Alexander Perniss, PhD, and Caitlin Wong, MS, who assist with sample processing and analysis.
Predictors of Persistence and Recovery from COVID-19 Anosmia
In the questionnaires, patients were asked whether they experienced phantosmia, also known as phantom smells, which is a condition that causes individuals to detect smells that aren’t present in the environment. Bankova found that cigarette smoke phantom smells are the sole predictor for the persistence of COVID-19 anosmia. Other phantom smells did not serve as predictors.
What she didn’t anticipate finding was that having environmental allergies predicted recovery. “Having persistent nasal inflammation from allergies makes you more likely to get your sense of smell back eventually,” says Bankova. “Having dust mite allergies is protective against developing the cigarette smoke phantom smells. So, this whole thing is linked pretty nicely, and it turned out that this really maybe is a predictor.”
The Path Forward
Although the future for patients with COVID-19 anosmia is still unclear, there is hope. Collaborating with Laidlaw, the pair has surveyed people with anosmia due to chronic rhinosinusitis to uncover how these patients experience different smells and flavors. They have been able to distinguish key differences unique to COVID-19 anosmia.
“If you think coffee is awesome smelling and you have no disruption of your sense of taste, this is more consistent with some sort of chronic rhinosinusitis and not with COVID-19 anosmia,” she said. “We’re getting to the point where clinically we can distinguish these syndromes with just questions.”
From the patient’s perspective, the research may soon become much simpler. Working with Mark Albers, MD, PhD, in the McCance Center for Brain Health at Massachusetts General Hospital, the pair hope to collaborate with an external partner to allow patients to complete testing at home using an app on their smartphone. Rather than having to visit the clinic in person, patients would be sent smell tests and record their observations through the app.
“We might be able to use this in combination with the clinical trial to track their response to therapy more easily at home,” she said.
While it may be easier to identify anosmia, current treatments only include nasal steroids, which haven’t been found to be very effective; Bankova makes it clear that improved treatment has a while to go.
“The initial hypothesis was that the virus destroyed some of the olfactory receptor neurons and disrupted the structure of the olfactory cilia, and I think, at this point, it’s becoming better and better recognized that this is not really the whole picture,” she said. “Today, there are numerous people who still suffer from this condition and have persistent inflammation, but it’s not the classical inflammation that you get with the chronic post-viral type or allergic nasal inflammation.” Anosmia is a unique aspect of COVID not associated with any other symptoms of the condition. While there is much to be done, Bankova is eager to uncover the mysteries of post-COVID anosmia and hopes for a future in which her patients will be able to smell again.