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Untangling the Myths and Mysteries of COVID-19

Brett L. Cucchiara, MD, estimates that a study he co-authored earlier this year, Acute Cerebrovascular Events in Hospitalized COVID-19 Patients, would have taken a year or more to conduct under normal circumstances. Instead, it took two months.

He credits his coauthors, Olivia Oldridge, PhD, and Hannah Schwennesen, BS —both students at the Perelman School of Medicine—for their swiftness. When the school closed at the onset of the pandemic, they volunteered to help.

“The speed with which we got this launched, collected the data, and analyzed it was pretty extraordinary,” says Dr. Cucchiara, Professor of Neurology at Penn Medicine and Director of the Neurovascular Ultrasound Laboratory at the Hospital of the University of Pennsylvania. “There was such a desperate desire to learn more about this disease. It was unlike anything I’ve experienced before in my career.”

Does COVID-19 Increase the Risk of Stroke?

For Dr. Cucchiara’s study, which was published in Stroke in July, he and his coauthors analyzed data from patients with COVID-19 admitted to the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, and Pennsylvania Hospital between March and May. They found that of the nearly 850 patients, 28 had suffered strokes.

A small case study published in The New England Journal of Medicine on April 28 identified large-vessel stroke as a presenting feature of COVID-19 in patients under 50-years-old. Accounts of other instances were cropping up on different news outlets.

“We really didn’t know whether this was going to turn out to be a big issue or not,” says Dr. Cucchiara. “At the time, it looked like we were on the cusp of an epidemic of stroke in young people with COVID.”

Instead, they found that not only was stroke a relatively rare occurrence among their COVID-19 patients, but most of those cases could be traced back to traditional stroke risk factors.

“The majority of them were older patients who had a lot of pre-existing risk factors, like high blood pressure and diabetes,” says Dr. Cucchiara.

That’s not to say, though, that the issue shouldn’t be explored.

“There clearly is some issue with the inflammatory response the body generates when there’s coronavirus infection that leads to more clotting. Forgetting about the specific infection, the mechanisms underlying that are really interesting. And I think they’re telling us something more, generally, about how people form blood clots and how that leads to heart attacks, strokes, and other clotting conditions,” Dr. Cucchiara says.

Can loss of smell predict the virus’s severity?

After some initial uncertainty, it now appears clear that anosmia, or loss of smell, is a symptom of COVID-19. With his study, which is being supported by a $197,357 grant from the NIH, Jay A. Gottfried, MD, PhD, is aiming to determine whether the degree of smell loss is at all tied to the severity of COVID-19.

“Our idea is to try to develop a predictive model so that we can establish whether or not patients with greater smell loss are more likely to go on to have more severe disease,” says Dr. Gottfried, a Penn Integrates Knowledge professor of Neurology in the Perelman School of Medicine and of Psychology in the School of Arts and Sciences. “If that holds true, that would help us prioritize which patients we might want to be treating or hospitalizing more urgently.”

Dr. Gottfried has studied the human sense of smell extensively. What makes this study pertinent, he says, is the olfactory system’s intimate access to the brain. “The nerve endings of olfactory cells in the nose can be directly contaminated by toxins, viruses, and other environmental signals, and then conveyed, almost like a trojan horse, right into the brain.”

Members of Dr. Gottfried’s lab have been recruiting participants at Penn Medicine’s drive-through testing site in West Philadelphia. His goal is to have 1,000 people with COVID-19 enrolled in the study.

A 12-item smell test, developed by Penn’s Richard L. Doty, PhD, and modified to be conducted entirely online, is administered to each participant on four separate occasions: the day of their COVID-19 test and then four, 12, and 60 days later. The more items missed on the test at each interval, the greater the loss of smell.

“Basically, we’re looking for a kind of smell biomarker,” Dr. Gottfried says. “Rather than putting people through a series of blood tests or an MRI scan, a smell test alone could stratify which patients need to be admitted to a hospital and prioritized for more intensive monitoring in case they require more aggressive clinical interventions.”

What can COVID-19 teach us?

For Joseph R. Berger, MD, FACP, FAAN, FANA, Professor of Neurology at Penn Medicine and Associate Chief of the MS Division, the goal now is to focus the ambition that spurred these studies and others that are currently in progress. Recently, he proposed that Penn establish a formal program within the Department of Neurology to study the neurologic complications associated with COVID-19.

“Penn Medicine is uniquely positioned in that it has a broad spectrum of experience and an incredible depth of expertise,” says Dr. Berger, a central figure in the study of the neurologic complications of HIV at the height of the HIV/AIDS global epidemic. “And there seems to be a more than adequate number of individuals who have an interest in understanding these complications. We have the capacity to make the kind of headway with COVID-19 that took a number of academic centers to accomplish with HIV.”

Penn Medicine, Philadelphia, PA 800-789-7366 © , The Trustees of the University of Pennsylvania

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