Smartwatches can track COVID-19 symptoms, study finds
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.
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.”
Drugs That Could Slow Aging May Hold Promise for Protecting the Elderly from COVID-19
Two recent human studies indicated that rapalogues increased resistance to the flu and decreased the severity of respiratory tract infections in older adults.
Although recent data has shown the coronavirus poses a greater risk to young people than previously understood, the ensuing COVID-19 disease is clearly far more dangerous for older people than it is for the young.
If we want to lower the COVID-19 fatality rate, we must also make fortifying our most vulnerable hosts a central part of our approach.
While our older adults have accrued tremendous knowledge, wisdom, and perspective over the years, their bodies have over time become less able to fight off viruses and other insults. The shorthand name for this increased susceptibility is aging.
We may have different names for the diseases which disproportionately kill us -- cancer, heart disease, and dementia among them – but what is really killing us is age. The older we are, the greater the chance we'll die from one or another of these afflictions. Eliminate any one completely - including cancer - and we won't on average live that much longer. But if we slow aging on a cellular level, we can counter all of these diseases at once, including COVID-19.
Every army needs both offensive and defensive capabilities. In our war against COVID-19, our offense strategy is to fight the virus directly. But strengthening our defense requires making us all more resistant to its danger. That's why everyone needs to be eating well, exercising, and remaining socially connected. But if we want to lower the COVID-19 fatality rate, we must also make fortifying our most vulnerable hosts a central part of our approach. That's where our new fight against this disease and the emerging science of aging intersect.
Once the domain of charlatans and delusionists, the millennia-old fantasy of extending our healthy lifespans has over the past century become real. But while the big jump in longevity around the world over the past hundred years or so is mostly attributable to advances in sanitation, nutrition, basic healthcare, and worker safety, advances over the next hundred will come from our increasing ability to hack the biology of aging itself.
A few decades ago, scientists began recognizing that some laboratory animals on calorie-restricted diets tended to live healthier, longer lives. Through careful experiments derived from these types of insights, scientists began identifying specific genetic, epigenetic, and metabolic pathways that influence how we age. A range of studies have recently suggested that systemic knobs might metaphorically be turned to slow the cellular aging process, making us better able to fight off diseases and viral attacks.
Among the most promising of these systemic interventions is a drug called metformin, which targets many of the hallmarks of aging and extends health span and lifespan in animals. Metformin has been around since the Middle Ages and has been used in Europe for over 60 years to treat diabetes. This five-cent pill became the most prescribed drug in the world after being approved by the FDA in 1994.
With so many people taking it, ever larger studies began suggesting metformin's positive potential effects preventing diabetes, cardiovascular diseases, cancer, and dementia. In fact, elderly people on metformin for their diabetes have around a 20 percent lower mortality than age-matched subjects without diabetes. Results like these led scientists to hypothesize that metformin wasn't just impacting a few individual diseases but instead having a systemic impact on entire organisms.
Another class of drug that seems to slow the systemic process of aging in animal models and very preliminary human trials inhibits a nutrient-sensing cellular protein called mTOR. A new category of drugs called rapalogues has been shown to extend healthspan and lifespan in every type of non-human animal so far tested. Two recent human studies indicated that rapalogues increased resistance to the flu and decreased the severity of respiratory tract infections in older adults.
If COVID-19 is primarily a severe disease of aging, then countering aging should logically go a long way in countering the disease.
These promising early indications have inspired a recently launched long-term study exploring how metformin and rapalogues might delay the onset of multiple, age-related diseases and slow the biological process of aging in humans. Under normal circumstances, studies like this seeking to crack the biological code of aging would continue to proceed slowly and carefully over years, moving from animal experiments to cautious series of human trials. But with deaths rising by the day, particularly of older people, these are not times for half measures. Wartimes have always demanded new ways of doing important things at warp speeds.
If COVID-19 is primarily a severe disease of aging, then countering aging should logically go a long way in countering the disease. We need to find out. Fast.
Although it would be a mistake for older people to just begin taking drugs like these without any indication, pushing to massively speed up our process for assessing whether these types of interventions can help protect older people is suddenly critical.
To do this, we need U.S. government agencies like the Department of Health and Human Services' Biomedical Advanced Research and Development Authority (BARDA) to step up. BARDA currently only funds COVID-19 clinical trials of drugs that can be dosed once and provide 60 days of protection. Metformin and rapalogues are not considered for BARDA funding because they are dosed once daily. This makes no sense because a drug that provides 60 days of protection from the coronavirus after a single dose does not yet exist, while metformin and rapalogues have already passed extensive safety tests. Instead, BARDA should consider speeding up trials with currently available drugs that could help at least some of the elderly populations at risk.
Although the U.S. Food and Drug Administration and Centers for Disease Control are ramping up their approval processes and even then needs to prioritize efforts, they too must find a better balance between appropriate regulatory caution and the dire necessities of our current moment. Drugs like metformin and rapalogues that have shown preliminary efficacy ought to be fast-tracked for careful consideration.
One day we will develop a COVID-19 vaccine to help everyone. But that could be at least a year from now, if not more. Until we get there and even after we do, speeding up our process of fortifying our older populations mush be a central component of our wartime strategy.
And when the war is won and life goes back to a more normal state, we'll get the added side benefit of a few more months and ultimately years with our parents and grandparents.
Antibody Testing Alone is Not the Key to Re-Opening Society
Immunity tests have too many unknowns right now to make them very useful in determining protective antibody status.
[Editor's Note: We asked experts from different specialties to weigh in on a timely Big Question: "How should immunity testing play a role in re-opening society?" Below, a virologist offers her perspective.]
With the advent of serology testing and increased emphasis on "re-opening" America, public health officials have begun considering whether or not people who have recovered from COVID-19 can safely re-enter the workplace.
"Immunity certificates cannot certify what is not known."
Conventional wisdom holds that people who have developed antibodies in response to infection with SARS-CoV-2, the coronavirus that causes COVID-19, are likely to be immune to reinfection.
For most acute viral infections, this is generally true. However, SARS-CoV-2 is a new pathogen, and there are currently many unanswered questions about immunity. Can recovered patients be reinfected or transmit the virus? Does symptom severity determine how protective responses will be after recovery? How long will protection last? Understanding these basic features is essential to phased re-opening of the government and economy for people who have recovered from COVID-19.
One mechanism that has been considered is issuing "immunity certificates" to individuals with antibodies against SARS-CoV-2. These certificates would verify that individuals have already recovered from COVID-19, and thus have antibodies in their blood that will protect them against reinfection, enabling them to safely return to work and participate in society. Although this sounds reasonable in theory, there are many practical reasons why this is not a wise policy decision to ease off restrictive stay-home orders and distancing practices.
Too Many Scientific Unknowns
Serology tests measure antibodies in the serum—the liquid component of blood, which is where the antibodies are located. In this case, serology tests measure antibodies that specifically bind to SARS-CoV-2 virus particles. Usually when a person is infected with a virus, they develop antibodies that can "recognize" that virus, so the presence of SARS-CoV-2 antibodies indicates that a person has been previously exposed to the virus. Broad serology testing is critical to knowing how many people have been infected with SARS-CoV-2, since testing capacity for the virus itself has been so low.
Tests for the virus measure amounts of SARS-CoV-2 RNA—the virus's genetic material—directly, and thus will not detect the virus once a person has recovered. Thus, the majority of people who were not severely ill and did not require hospitalization, or did not have direct contact with a confirmed case, will not test positive for the virus weeks after they have recovered and can only determine if they had COVID-19 by testing for antibodies.
In most cases, for most pathogens, antibodies are also neutralizing, meaning they bind to the virus and render it incapable of infecting cells, and this protects against future infections. Immunity certificates are based on the assumption that people with antibodies specific for SARS-CoV-2 will be protected against reinfection. The problem is that we've only known that SARS-CoV-2 existed for a little over four months. Although studies so far indicate that most (but not all) patients with confirmed COVID-19 cases develop antibodies, we don't know the extent to which antibodies are protective against reinfection, or how long that protection will last. Immunity certificates cannot certify what is not known.
The limited data so far is encouraging with regard to protective immunity. Most of the patient sera tested for antibodies show reasonable titers of IgG, the type of antibodies most likely to be neutralizing. Furthermore, studies have shown that these IgG antibodies are capable of neutralizing surrogate viruses as well as infectious SARS-CoV-2 in laboratory tests. In addition, rhesus monkeys that were experimentally infected with SARS-CoV-2 and allowed to recover were protected from reinfection after a subsequent experimental challenge. These data tentatively suggest that most people are likely to develop neutralizing IgG, and protective immunity, after being infected by SARS-CoV-2.
However, not all COVID-19 patients do produce high levels of antibodies specific for SARS-CoV-2. A small number of patients in one study had no detectable neutralizing IgG. There have also been reports of patients in South Korea testing PCR positive after a prior negative test, indicating reinfection or reactivation. These cases may be explained by the sensitivity of the PCR test, and no data have been produced to indicate that these cases are genuine reinfection or recurrence of viral infection.
Complicating matters further, not all serology tests measure antibody titers. Some rapid serology tests are designed to be binary—the test can either detect antibodies or not, but does not give information about the amount of antibodies circulating. Based on our current knowledge, we cannot be certain that merely having any level of detectable antibodies alone guarantees protection from reinfection, or from a subclinical reinfection that might not cause a second case of COVID-19, but could still result in transmission to others. These unknowns remain problematic even with tests that accurately detect the presence of antibodies—which is not a given today, as many of the newly available tests are reportedly unreliable.
A Logistical and Ethical Quagmire
While most people are eager to cast off the isolation of physical distancing and resume their normal lives, mere desire to return to normality is not an indicator of whether those antibodies actually work, and no certificate can confer immune protection. Furthermore, immunity certificates could lead to some complicated logistical and ethical issues. If antibodies do not guarantee protective immunity, certifying that they do could give antibody-positive people a false sense of security, causing them to relax infection control practices such as distancing and hand hygiene.
"We should not, however, place our faith in assumptions and make return to normality contingent on an arbitrary and uninformative piece of paper."
Certificates could be forged, putting susceptible people at higher exposure risk. It's not clear who would issue them, what they would entitle the bearer to do or not do, or how certification would be verified or enforced. There are many ways in which such certificates could be used as a pretext to discriminate against people based on health status, in addition to disability, race, and socioeconomic status. Tracking people based on immune status raises further concerns about privacy and civil rights.
Rather than issuing documents confirming immune status, we should instead "re-open" society cautiously, with widespread virus and serology testing to accurately identify and isolate infected cases rapidly, with immediate contact tracing to safely quarantine and monitor those at exposure risk. Broad serosurveillance must be coupled with functional assays for neutralization activity to begin assessing how protective antibodies might actually be against SARS-CoV-2 infection. To understand how long immunity lasts, we should study antibodies, as well as the functional capabilities of other components of the larger immune system, such as T cells, in recovered COVID-19 patients over time.
We should not, however, place our faith in assumptions and make return to normality contingent on an arbitrary and uninformative piece of paper. Re-opening society, the government, and the economy depends not only on accurately determining how many people have antibodies to SARS-CoV-2, but on a deeper understanding of how those antibodies work to provide protection.