If a COVID-19 infection develops, a wearable device may eventually be able to clue you in. A study at the University of Michigan found that a smartwatch can monitor how symptoms progress.
The study evaluated the effects of COVID-19 with various factors derived from heart-rate data. This method also could be employed to detect other diseases, such as influenza and the common cold, at home or when medical resources are limited, such as during a pandemic or in developing countries.
Tracking students and medical interns across the country, the University of Michigan researchers found that new signals embedded in heart rate indicated when individuals were infected with COVID-19 and how ill they became.
For instance, they discovered that individuals with COVID-19 experienced an increase in heart rate per step after the onset of their symptoms. Meanwhile, people who reported a cough as one of their COVID-19 symptoms had a much more elevated heart rate per step than those without a cough.
“We previously developed a variety of algorithms to analyze data from wearable devices. So, when the COVID-19 pandemic hit, it was only natural to apply some of these algorithms to see if we can get a better understanding of disease progression,” says Caleb Mayer, a doctoral student in mathematics at the University of Michigan and a co-first author of the study.
People may not internally sense COVID-19’s direct impact on the heart, but “heart rate is a vital sign that gives a picture of overall health," says Daniel Forger, a University of Michigan professor.
Millions of people are tracking their heart rate through wearable devices. This information is already generating a tremendous amount of data for researchers to analyze, says co-author Daniel Forger, professor of mathematics and research professor of computational medicine and bioinformatics at the University of Michigan.
“Heart rate is affected by many different physiological signals,” Forger explains. “For instance, if your lungs aren’t functioning properly, your heart may need to beat faster to meet metabolic demands. Your heart rate has a natural daily rhythm governed by internal biological clocks.” While people may not internally sense COVID-19’s direct impact on the heart, he adds that “heart rate is a vital sign that gives a picture of overall health.”
Among the total of 2,164 participants who enrolled in the student study, 72 undergraduate and graduate students contracted COVID-19, providing wearable data from 50 days before symptom onset to 14 days after. The researchers also analyzed this type of data for 43 medical interns from the Intern Health Study by the Michigan Neuroscience Institute and 29 individuals (who are not affiliated with the university) from the publicly available dataset.
Participants could wear the device on either wrist. They also documented their COVID-19 symptoms, such as fever, shortness of breath, cough, runny nose, vomiting, diarrhea, body aches, loss of taste, loss of smell, and sore throat.
Experts not involved in the study found the research to be productive. “This work is pioneering and reveals exciting new insights into the many important ways that we can derive clinically significant information about disease progression from consumer-grade wearable devices,” says Lisa A. Marsch, director of the Center for Technology and Behavioral Health and a professor in the Geisel School of Medicine at Dartmouth College. “Heart-rate data are among the highest-quality data that can be obtained via wearables.”
Beyond the heart, she adds, “Wearable devices are providing novel insights into individuals’ physiology and behavior in many health domains.” In particular, “this study beautifully illustrates how digital-health methodologies can markedly enhance our understanding of differences in individuals’ experience with disease and health.”
Previous studies had demonstrated that COVID-19 affects cardiovascular functions. Capitalizing on this knowledge, the University of Michigan endeavor took “a giant step forward,” says Gisele Oda, a researcher at the Institute of Biosciences at the University of Sao Paulo in Brazil and an expert in chronobiology—the science of biological rhythms. She commends the researchers for developing a complex algorithm that “could extract useful information beyond the established knowledge that heart rate increases and becomes more irregular in COVID patients.”
Wearable devices open the possibility of obtaining large-scale, long, continuous, and real-time heart-rate data on people performing everyday activities or while sleeping. “Importantly, the conceptual basis of this algorithm put circadian rhythms at the center stage,” Oda says, referring to the physical, mental, and behavioral changes that follow a 24-hour cycle. “What we knew before was often based on short-time heart rate measured at any time of day,” she adds, while noting that heart rate varies between day and night and also changes with activity.
However, without comparison to a control group of people having the common flu, it is difficult to determine if the heart-rate signals are unique to COVID-19 or also occur with other illnesses, says John Torous, an assistant professor of psychiatry at Harvard Medical School who has researched wearable devices. In addition, he points to recent data showing that many wearables, which work by beaming light through the skin, may be less accurate in people with darker skin due to variations in light absorption.
While the results sound interesting, they lack the level of conclusive evidence that would be needed to transform how physicians care for patients. “But it is a good step in learning more about what these wearables can tell us,” says Torous, who is also director of digital psychiatry at Beth Israel Deaconess Medical Center, a Harvard affiliate, in Boston. A follow-up step would entail replicating the results in a different pool of people to “help us realize the full value of this work.”
It is important to note that this research was conducted in university settings during the early phases of the pandemic, with remote learning in full swing amid strict isolation and quarantine mandates in effect. The findings demonstrate that physiological monitoring can be performed using consumer-grade wearable sensors, allowing research to continue without in-person contact, says Sung Won Choi, a professor of pediatrics at the University of Michigan who is principal investigator of the student study.
“The worldwide COVID-19 pandemic interrupted a lot of activities that relied on face-to-face interactions, including clinical research,” Choi says. “Mobile technology proved to be tremendously beneficial during that time, because it allowed us to collect detailed physiological data from research participants remotely over an entire semester.” In fact, the researchers did not have any in-person contact with the students involved in the study. “Everything was done virtually," Choi explains. "Importantly, their willingness to participate in research and share data during this historical time, combined with the capacity of secure cloud storage and novel mathematical analytics, enabled our research teams to identify unique patterns in heart-rate data associated with COVID-19.”
At age 52, Glen Rouse suffered from arm weakness and a lot of muscle twitches. “I first thought something was wrong when I could not throw a 50-pound bag of dog food over the tailgate of my truck—something I use to do effortlessly,” said the 54-year-old resident of Anderson, California, about three hours north of San Francisco.
In August, Rouse retired as a forester for a private timber company, a job he had held for 31 years. The impetus: amyotrophic lateral sclerosis, or ALS, a progressive neuromuscular disease that is commonly known as Lou Gehrig’s disease, named after the New York Yankees’ first baseman who succumbed to it less than a month shy of his 38th birthday in 1941. ALS eventually robs an individual of the ability to talk, walk, chew, swallow and breathe.
Rouse is now dependent on ventilation through a nasal mask and uses a powerchair to get around. “I can no longer walk or use my arms very well,” he said. “I can still move my wrists and fingers. I can also transfer from my chair to the toilet if I have two of my friends help me.”
It’s “shocking” that modern medicine has very little to offer to people with this devastating condition, Rouse said. But there is hope on the horizon. Yesterday, the U.S. Food and Drug Administration approved Relyvrio, a drug made up of two parts, sodium phenylbutyrate and taurursodiol, to treat patients with ALS.
“This approval provides another important treatment option for ALS, a life-threatening disease that currently has no cure,” said Billy Dunn, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, in a statement. “The FDA remains committed to facilitating the development of additional ALS treatments.”
Until this point, the FDA had approved only two other medications—Riluzole (rilutek) in 1995 and Radicava (edaravone) in 2017—to extend life in patients with ALS, which typically kills within two to five years after diagnosis. That’s why earlier this week, Rouse was optimistic about the FDA’s likely approval of a controversial new drug for ALS.
When Relyvrio is taken in addition to Riluzole, it appears to slow functional decline by an additional 25 percent and extend life by another 6 to 10 months, said Richard Bedlak, director of the Duke ALS Clinic. “It is not a cure, but it is definitely a step forward.”
“The whole ALS community is extremely excited about it,” he said the day before Relyvrio’s expected approval. “We are very hopeful. We’re on pins and needles.”
A study of 137 ALS patients did not result in “substantial evidence” that Relyvrio was effective, the agency’s Peripheral and Central Nervous System Drugs Advisory Committee concluded in March. However, after some persuasion from FDA officials, patients and their families, the committee met again and decided to recommend approving the drug.
In January 2019, following an ALS diagnosis at age 58 in October the previous year, Jeff Sarnacki, of Chester, Maryland, was accepted into a trial for Relyvrio. “Because of the trial, we did experience hope and a greater sense of help than had we not had that opportunity,” said Juliet Taylor, his wife and caregiver. They both believed the drug “worked for him in giving him more time.”
In June 2019, Sarnacki chose an open-label extension, offered to patients by drug researchers after a study ends, and took the active drug until he died peacefully at home under hospice care in May 2020, five days after his 60th birthday. A retired agent with the federal Bureau of Alcohol, Tobacco, Firearms and Explosives who later worked as a security consultant, Sarnacki lived about 19 months after diagnosis, which is shorter than the typical prognosis.
His symptoms began with leg cramps in fall 2017 and foot drop in early 2018. A feeding tube was placed in 2019, as it became necessary early in his illness, Taylor said. He also took Radicava and Riluzole, the two previously approved drugs, for his ALS. “We were both incredulous that, so many years after Lou Gehrig’s own diagnosis, there were so few treatments available,” she said.
The dearth of successful treatments for ALS is “certainly not for lack of trying,” said Karen Raley Steffens, a registered nurse and ALS support services coordinator at the Les Turner ALS Foundation in Skokie, Ill. “There are thousands of researchers and scientists all over the world working tirelessly to try to develop treatments for ALS.”
Unfortunately, she added, research takes time and exorbitant amounts of funding, while bureaucratic challenges persist. The rare disease also manifests and progresses in many different ways, so many treatments are needed.
As of 2017, the Centers for Disease Control and Prevention estimated that more than 31,000 people in the U.S. live with ALS, and an average of 5,000 people are newly diagnosed every year. It is slightly more common in men than women. Most people are diagnosed between the ages of 55 and 75.
Most cases of ALS are sporadic, meaning that doctors don’t know the cause. There is about a one-year interval between symptom onset and an ALS diagnosis for most patients, so many motor neurons are lost by the time individuals can enroll in a clinical trial, said Richard Bedlack, professor of neurology and director of the Duke ALS Clinic in Durham, North Carolina.
Bedlack found the new drug, Relyvrio, to be “very promising,” which is why he testified to the FDA in favor of approval. (He’s a consultant and disease state speaker for multiple companies including Amylyx, manufacturer of Relyvrio.)
The “drug has different mechanisms of action than the currently approved treatments,” Bedlack said. He added that, when Relyvrio is taken in addition to Riluzole, it appears to slow functional decline by an additional 25 percent and extend life by another 6 to 10 months. “It is not a cure, but it is definitely a step forward.”
T. Scott Diesing, a neurohospitalist and director of general neurology at the University of Nebraska Medical Center in Omaha, said he hopes the drug is “as good as people anticipated it should be, because there are not too many options for these patients.”
"FDA went out on a limb in approving Relyvrio based on limited results from a small trial while a larger study remains in progress," said Florian P. Thomas, co-director of the ALS Center at Hackensack University Medical Center and the Meridian School of Medicine. "While it is definitely promising, clearly, the last word on this drug has not been spoken."
So far, Rouse's voice is holding up, but he knows the day will come when ALS will steal that and much more from him.
ALS is 100 percent fatal, with some patients dying as soon as a year after diagnosis. A few have lasted as long as 15 years, but those are the exceptions, Diesing said.
“If this drug can provide even months of additional life, or would maintain quality of life, that’s a big deal,” he noted, adding that “the patients are saying, ‘I know it’s not proven conclusively, but what do we have to lose?’ So, they would like to try it while additional studies are ongoing.” The drug has already been conditionally approved in Canada.
As his disease progresses, Rouse hopes to get a speech-to-text voice-generating computer that he can control with his eyes. So far, his voice is holding up, but he knows the day will come when ALS will steal that and much more from him. He works at I AM ALS, a patient-led community, and six of his friends have already died of the disease.
“Every time I lose a friend to ALS, I grieve and am sad but I resolve myself to keep working harder for them, myself and others,” Rouse said. “People living with ALS find great purpose in life advocating and trying to make a difference.”
The Friday Five covers important stories in health and science research that you may have missed - usually over the previous week, but today's episode is a lookback on important studies over the month of September.
Most recently, on September 27, pharmaceuticals Biogen and Eisai announced that a clinical trial showed their drug, lecanemab, can slow the rate of Alzheimer's disease. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend and the new month.
This Friday Five episode covers the following studies published and announced over the past month:
- A new drug is shown to slow the rate of Alzheimer's disease
- The need for speed if you want to reduce your risk of dementia
- How to refreeze the north and south poles
- Ancient wisdom about Neti pots could pay off for Covid
- Two women, one man and a baby