John “Jack” Finlay ’18, an M.D. and Ph.D. student at Duke University, recently published a paper in Science Translational Medicine about a frightening facet of long COVID — persistent loss of smell. In a recent interview with PAW, he discussed his findings and whether and how this strange condition might be treated.
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What did you study for this paper, and why?
When the pandemic first started and lots of people were getting COVID, one of the early signs symptomatically was loss of smell. The virus kills off some support cells. The support cells [usually] regenerate, and the tissue that’s responsible for smell (the upper part of your nose) that epithelium just regenerates. It’s a peripheral process.
We had a pretty good understanding of why that happens in the short term. However, many patients were going for months, years even, [without regaining] their sense of smell.
Why did you focus on smell?
There are a handful of symptoms that go along with long COVID — loss of smell, shortness of breath, and brain fog. You are not going to go in and biopsy their lung or brain. The nose offers a nice insight into the body. We recruited patients from all over the country and took a biopsy of their tissue where normally where we would find the olfactory epithelium/tissue, which houses the neurons that are able to smell.
We did single-cell RNA sequencing on the biopsies. It allows you to profile the expression of every single gene within every single cell of your body. You can classify the cells and the activation states of those cells: how they look, what they are doing. If you have a T-cell, an immune cell, is that immune cell activated? Does it look like it’s responding to something or hanging out? We generated all this data, integrated it among all these patients, and then looked for common patterns.
One of the first stark trends is persistent immune infiltrate, specifically in their olfactory epithelium. We were able to pin this down to a specific type of T-cell, which seems to be contributing to ongoing inflammation.
We found significantly fewer mature olfactory sensory neurons in the patients who couldn’t smell. This ongoing inflammation is inhibiting the normal process of neural turnover in your nose. These neurons can’t continue to develop because they are seeing all this inflammation.
Could that change or be treated?
The good news is that there were some mature neurons. The inflammation wasn’t so bad, there is hope that the olfactory epithelium wasn’t totally damaged. If we can modulate this inflammation, kind of tone it down a little bit, we might be able to restore regeneration of neurons in these patients.
If the body is acting like it is still fighting the virus, does the patient still have COVID?
We couldn’t find any signs of active viral infection. It looks like the virus is gone. But the T-cells are almost acting as if it’s still there. They are tricked into this maintenance state, just hanging out in the olfactory epithelium, promoting inflammation to fight a virus they don’t have anymore.
What are the next steps? Treatment?
There are a lot of immunomodulatory drugs that can treat [inflammation]. Some have been tried on COVID smell loss. We think a more local delivery of some steroids up into the superior part of the nose [could work].
It’s been fascinating talking to patients about their daily experience. Many develop eating disorders or weight loss. They don’t like food; they don’t enjoy it. Smell loss in general has been associated with developing depression. The sense of smell is central to people. You don’t realize how much you utilize it until you lose it.
—Interview conducted and condensed by Nicholas DeVito
Diverging from his fellow Republicans, Wisconsin Rep. Mike Gallagher ’06 said continuing to financially support Ukraine in its war against Russia is “a sound investment in U.S. national security.” — WPR
Brookings Institution senior fellow Michael O’Hanlon ’82 *91 said while the incremental approach to supplying Ukraine with weapons has been wise, he’s “in favor of sending hundreds of Western tanks as soon as possible.” — The Washington Post
Author Eric Schlosser ’81 said if Russia defeats Ukraine using threats of nuclear action, “Russia may use them to coerce other states. Tactics once considered immoral and unthinkable might become commonplace.” — The Atlantic
NPR reporter Frank Langfitt ’86 will become the outlet’s new global democracy correspondent, working with the investigations team in Washington, D.C. — NPR
Conservative columnist John Stossel ’69 said recycling is costly and often causes more pollution than you’d think: “Recycling paper (or cardboard) does save trees. Recycling aluminum does save energy. But that’s about it.” — The New York Post
Journalist and Nobel Peace Prize winner Maria Ressa ’86 was acquitted of four tax evasion charges the Philippine government had brought against her. She called it a “victory for journalists,” but she still faces three other cases including the appeal of a cyber libel conviction. — CBS News
Ilya Shapiro ’99 and Christopher Rufo, both of the conservative Manhattan Institute think tank, suggested four steps legislators can take to “restore free speech and academic freedom” in higher education, all aimed at diversity initiatives. — The Wall Street Journal
Andrea Campbell ’04 was sworn in as Massachusetts attorney general, a position where she plans to create an office of gun safety enforcement and a reproductive justice unit. — WBUR
“If diversity trainings have no impact whatsoever, that would mean that perhaps billions of dollars are being wasted annually in the United States on these efforts. But there’s a darker possibility: Some diversity initiatives might actually worsen the D.E.I. climates of the organizations that pay for them.”
— Author Jesse Singal *13, discussing the dearth of studies supporting diversity trainings and suggesting different strategies that might be more effective. — The New York Times
Princeton trustee and Missouri School of Journalism professor Kathy Kiely ’77 said allowing C-SPAN to continue broadcasting live from the House would allow the American public to see “the real drama that happens on the floor,” and if the Senate did the same, more senators would show up to debate. — KBIA
The Wall Street Journal wrote in an editorial that former Indiana governor and Purdue University president Mitch Daniels ’71 is favored for a 2024 U.S. Senate race, but already conservatives are running ads attacking him “because his politics of restraint and compromise is now declasse in some corners of the GOP.” — The Wall Street Journal
The Root listed author Morgan Jerkins ’14 among “the most power Black voices on Twitter.” — The Root
In building Amazon, Jeff Bezos ’86 employed an ancient and effective tactic: the metaphor as a mental shortcut. — Inc. Magazine
A new documentary titled Pretty Baby examines how actress Brooke Shields ’87 grew up in the spotlight. It will debut at the Sundance festival and stream on Hulu. — Good Morning America
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