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Topics: Five Questions, Funding, Pilot Funding

Right Place, Right Time: Taking on COVID Loss of Smell

Five Questions with Lora Bankova on a physician-scientist’s dream come true.

Lora Bankova, MD, described her translational research on COVID anosmia (loss of smell) as a dream come true for a physician-scientist. She feels this way because her research enables a dynamic interplay between bench research and “bedside” clinical care. But that’s not what this physician-scientist set out to do.

As an allergist/immunologist, Bankova, an assistant professor of medicine and associate physician at Brigham and Women’s Hospital (BWH), expected to be studying the lungs, not the nose – and certainly not COVID anosmia. Then her research on allergic inflammation crossed hairs with one of the hottest research questions of the early pandemic: What’s up with COVID-associated loss of smell?

Bankova was in the right place at the right time. She jumped on the opportunity to expand her work into this new but overlapping research focus. Harvard Catalyst’s Five Senses: Input and Response funding opportunity was there at the right time too, offering her the support needed to take the work to the next level and lay the groundwork for a larger NIH grant.

Your Five Senses pilot funding targeted COVID-related smell and taste dysfunction, but that wasn’t your primary focus prior to COVID. How did you end up studying this?

I am an allergist and immunologist; my main focus is to understand how the immune response in the airways gets skewed toward allergic inflammation. Why is it that some people inhale pollen or other allergens and only have a few sneezes while others have a persistent inflammation? I was studying different models to try to understand the involvement of epithelial cells, specifically, a unique chemosensory type called the tuft cell.

What was interesting was that we found these cells to be very abundant in the nose and very rare in the lower airways. So while most research in allergies focuses on the lung, with this data, I started looking in the nose. That led me to a big dataset of olfactory mucosa that I received during the COVID shutdown to look for evidence of these tuft cells.

This was around the time that many people were losing their sense of smell from COVID infection, and we started looking in our dataset for clues. I guess word got out that I have a research interest in this area and patients who had lost their sense of smell started coming to our Allergy & Immunology Clinic at BWH, hoping we could help them. So we decided to do a small study to try to understand what was going on, collecting and analyzing nasal swabs on a cohort of about 10 patients.

Your initial small study quickly grew. How did that happen?

“[The funding] enabled us to process the samples we had but also collect a few more and do single-cell analysis on fresh samples. Without that, the study probably wouldn’t have had as much impact because we wouldn’t have analyzed as many samples and might have missed some findings we now have.”

I had just received the IRB approval for the study when the BWH media department reached out to me about it. I described some of the patients’ experiences, and the story got picked up by a local news station. All of a sudden people from all over the U.S. were reaching out to us wanting to donate samples and share their own experiences. Some of their providers were downplaying their anosmia as insignificant, and they wanted their experiences to be validated.

Over three months, we collected samples from dozens of people and our small study of 10 grew to 60.  I had funding from my department for the startup, but doing lipidomic analysis, protein analysis, sequencing, and similar processes is very expensive. We didn’t have the money to process that many samples.

That’s when the Five Senses grant was announced. I applied pretty much saying: “I have all these samples and no money to process them. Would you give us money?” The funding was critical because it helped me get to the next level. It enabled us to process the samples we had but also collect a few more and do single-cell analysis on fresh samples. Without that, the study probably wouldn’t have had as much impact because we wouldn’t have analyzed as many samples and might have missed some findings we now have. It came at the right time.

Where are you now in this line of research?

We have two study arms that came out of the pilot. One was sparked by the media coverage. Because so many patients reached out, we have generated a database where people can fill out a standardized questionnaire capturing what they experience in their daily life. So far we have data from more than 400 people with COVID dysosmia and/or dysgeusia (loss of taste), showing the unique characteristics of these conditions and validating them as real. That’s important because many patients have been hearing–some of them for three years–that it’s not real, that it’s all in their heads.

The other arm is the mechanistic study, which we’re still working on because there are just so many new things we’re learning there. We have some surprising findings about the unique properties of the inflammatory cells in the nose of patients with COVID-19 olfactory dysfunction we need to verify. We’re delving deeper into their function and their mechanisms of action to narrow down therapeutic targets that will hopefully lead to some kind of treatment.

Because that’s the goal, right? Not just to study but to treat people. I see these patients in clinic, and I would like to tell them that we’ve finally found something that will help them feel better.

How does that clinical goal motivate your research?

“It’s a bit of a dream come true for any physician-scientist to have this situation where you can learn from your patients, apply what you’ve learned to your research, and then hopefully find treatments for the conditions they have.”

I’m a physician, right? I came into research thinking, like most physician-scientists, that I’d like to have a clinical problem that I can solve by doing some lab research and then taking that back to the clinic to help people recover.

It was much more difficult to find the clinical utility of what I was doing before this study, because I was working with mouse models trying to find a role for a  particular type of cell. Explaining to people the actual impact or importance of that work was sort of challenging.

In contrast, the COVID anosmia study was an occasion to see the immediate connection between my research work and my clinical work. Now it just keeps me more excited and more motivated, because I see hope that eventually this will translate into something that will help my own patients. It’s a bit of a dream come true for any physician-scientist to have this situation where you can learn from your patients, apply what you’ve learned to your research, and then hopefully find treatments for the conditions they have.

As a young investigator in a transition phase toward building your own independently funded lab, running studies, seeing patients, chasing funding, and more, how do you find work/life balance?

I can’t say that it hasn’t been without challenges. I think the main thing that’s kept me going is that in my division, we are very supportive of one another. I don’t think it works otherwise.

The anosmia study has been a somewhat lucky situation in that the funding from Harvard Catalyst came at the right time to help secure NIH funding, but my other research projects are following a more protracted timeline. Grant funding is difficult, and involves a great deal of writing and rewriting.

My division head, Joshua Boyce, MD, and my former mentor, Nora Barrett, MD, are very supportive, and my coworkers are excited to talk about this research. It’s fun to just walk down to the water fountain and chat along the way about what we found today. We celebrate one another’s results or good news. It’s really like a family. I don’t think I would have survived without that.

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