An At-Home Contagiousness Test for COVID-19 Already Exists. Why Can’t We Use It?
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
You're lying in bed late at night, the foggy swirl of the pandemic's 8th month just beginning to fall behind you, when you detect a slight tickle at the back of your throat.
"If half of people choose to use these tests every other day, then we can stop transmission faster than a vaccine can."
Suddenly fully awake, a jolt of panicked electricity races through your body. Has COVID-19 come for you? In the U.S., answering this simple question is incredibly difficult.
Now, you might have to wait for hours in line in your car to get a test for $100, only to find out your result 10-14 days later -- much too late to matter in stopping an outbreak. Due to such obstacles, a recent report in JAMA Internal Medicine estimated that 9 out of 10 infections in the U.S. are being missed.
But what if you could use a paper strip in the privacy of your own home, like a pregnancy test, and find out if you are contagious in real time?
e25 Bio, a small company in Cambridge, Mass., has already created such a test and it has been sitting on a lab bench, inaccessible, since April. It is an antigen test, which looks for proteins on the outside of a virus, and can deliver results in about 15 minutes. Also like an over-the-counter pregnancy test, e25 envisions its paper strips as a public health screening tool, rather than a definitive diagnostic test. People who see a positive result would be encouraged to then seek out a physician-administered, gold-standard diagnostic test: the more sensitive PCR.
Typically, hospitals and other health facilities rely on PCR tests to diagnose viruses. This test can detect small traces of genetic material that a virus leaves behind in the human body, which tells a clinician that the patient is either actively infected with or recently cleared that virus. PCR is quite sensitive, meaning that it is able to detect the presence of a virus' genetic material very accurately.
But although PCR is the gold-standard for diagnostics, it's also the most labor-intensive way to test for a virus and takes a relatively long time to produce results. That's not a good match for stopping super-spreader events during an unchecked pandemic. PCR is also not great at identifying the infected people when they are most at risk of potentially transmitting the virus to others.
That's because the viral threshold at which PCR can detect a positive result is so low, that it's actually too sensitive for the purposes of telling whether someone is contagious.
"The majority of time someone is PCR positive, those [genetic] remnants do not indicate transmissible virus," epidemiologist Michael Mina recently Tweeted. "They indicate remnants of a recently cleared infection."
To stop the chain of transmission for COVID-19, he says, "We need a more accurate test than PCR, that turns positive when someone is able to transmit."
In other words, we need a test that is better at detecting whether a person is contagious, as opposed to whether a small amount of virus can be detected in their nose or saliva. This kind of test is especially critical given the research showing that asymptomatic and pre-symptomatic people have high viral loads and are spreading the virus undetected.
The critical question for contagiousness testing, then, is how big a dose of SARS-CoV-2, the virus that causes COVID, does it take to infect most people? Researchers are still actively trying to answer this. As Angela Rasmussen, a coronavirus expert at Columbia University, told STAT: "We don't know the amount that is required to cause an infection, but it seems that it's probably not a really, really small amount, like measles."
Amesh Adalja, an infectious disease physician and a senior scholar at the Johns Hopkins University Center for Health Security, told LeapsMag: "It's still unclear what viral load is associated with contagiousness but it is biologically plausible that higher viral loads, in general, are associated with more efficient transmission especially in symptomatic individuals. In those without symptoms, however, the same relationship may not hold and this may be one of the reasons young children, despite their high viral loads, are not driving outbreaks."
"Antigen tests work best when there's high viral loads. They're catching people who are super spreaders."
Mina and colleagues estimate that widespread use of weekly cheap, rapid tests that are 100 times less sensitive than PCR tests would prevent outbreaks -- as long as the people who are positive self-isolate.
So why can't we buy e25Bio's test at a drugstore right now? Ironically, it's barred for the very reason that it's useful in the first place: Because it is not sensitive enough to satisfy the U.S. Food and Drug Administration, according to the company.
"We're ready to go," says Carlos-Henri Ferré, senior associate of operations and communications at e25. "We've applied to FDA, and now it's in their hands."
The problem, he said, is that the FDA is evaluating applications for antigen tests based on criteria for assessing diagnostics, like PCR, even when the tests serve a different purpose -- as a screening tool.
"Antigen tests work best when there's high viral loads," Ferré says. "They're catching people who are super spreaders, that are capable of continuing the spread of disease … FDA criteria is for diagnostics and not this."
FDA released guidance on July 29th -- 140 days into the pandemic -- recommending that at-home tests should perform with at least 80 percent sensitivity if ordered by prescription, and at least 90 percent sensitivity if purchased over the counter. "The danger of a false negative result is that it can contribute to the spread of COVID-19," according to an FDA spokesperson. "However, oversight of a health care professional who reviews the results, in combination with the patient's symptoms and uses their clinical judgment to recommend additional testing, if needed, among other things, can help mitigate some risks."
Crucially, the 90 percent sensitivity recommendation is judged upon comparison to PCR tests, meaning that if a PCR test is able to detect virus in 100 samples, the at-home antigen test would need to detect virus in at least 90 of those samples. Since antigen tests only detect high viral loads, frustrated critics like Mina say that such guidance is "unreasonable."
"The FDA at this moment is not understanding the true potential for wide-scale frequent testing. In some ways this is not their fault," Mina told LeapsMag. "The FDA does not have any remit to evaluate tests that fall outside of medical diagnostic testing. The proposal I have put forth is not about diagnostic testing (leave that for symptomatic cases reporting to their physician and getting PCR tests)....Daily rapid tests are not about diagnosing people and they are not about public health surveillance and they are not about passports to go to school, out to dinner or into the office. They are about reducing population-level transmission given a similar approach as vaccines."
A reasonable standard, he added, would be to follow the World Health Organization's Target Product Profiles, which are documents to help developers build desirable and minimally acceptable testing products. "A decent limit," Mina says, "is a 70% or 80% sensitivity (if they truly require sensitivity as a metric) to detect virus at Ct values less than 25. This coincides with detection of the most transmissible people, which is important."
(A Ct value is a type of measurement that corresponds inversely to the amount of viral load in a given sample. Researchers have found that Ct values of 13-17 indicate high viral load, whereas Ct values greater than 34 indicate a lack of infectious virus.)
"We believe this should be an at-home test, but [if FDA approval comes through] the first rollout is to do this in laboratories, hospitals, and clinics."
"We believe that population screening devices have an immediate place and use in helping beat the virus," says Ferré. "You can have a significant impact even with a test at 60% sensitivity if you are testing frequently."
When presented with criticism of its recommendations, the FDA indicated that it will not automatically deny any at-home test that fails to meet the 90 percent sensitivity guidance.
"FDA is always open to alternative proposals from developers, including strategies for serial testing with less sensitive tests," a spokesperson wrote in a statement. "For example, it is possible that overall sensitivity of the strategy could be considered cumulatively rather than based on one-time testing….In the case of a manufacturer with an at-home test that can only detect people with COVID-19 when they have a high viral load, we encourage them to talk with us so we can better understand their test, how they propose to use it, and the validation data they have collected to support that use."
However, the FDA's actions so far conflict with its stated openness. e25 ended up adding a step to the protocol in order to better meet FDA standards for sensitivity, but that extra step—sending samples to a laboratory for results—will undercut the test's ability to work as an at-home screening tool.
"We believe this should be an at-home test, but [if FDA approval comes through] the first rollout is to do this in laboratories, hospitals, and clinics," Ferré says.
According to the FDA, no test developers have approached them with a request for an emergency use authorization that proposes an alternate testing paradigm, such as serial testing, to mitigate test sensitivity below 80 percent.
From a scientific perspective, antigen tests like e25Bio's are not the only horse in the race for a simple rapid test with potential for at-home use. CRISPR technology has long been touted as fertile ground for diagnostics, and in an eerily prescient interview with LeapsMag in November, CRISPR pioneer Feng Zhang spoke of its potential application as an at-home diagnostic for an infectious disease specifically.
"I think in the long run it will be great to see this for, say, at-home disease testing, for influenza and other sorts of important public health [concerns]," he said in the fall. "To be able to get a readout at home, people can potentially quarantine themselves rather than traveling to a hospital and then carrying the risk of spreading that disease to other people as they get to the clinic."
Zhang's company Sherlock Biosciences is now working on scaled-up manufacturing of a test to detect SARS CoV-2. Mammoth Biosciences, which secured funding from the National Institutes of Health's Rapid Acceleration of Diagnostics program, is also working on a CRISPR diagnostic for SARS CoV-2. Both would check the box for rapid testing, but so far not for at-home testing, as they would also require laboratory infrastructure to provide results.
If any at-home tests can clear the regulatory hurdles, they would also need to be manufactured on a large scale and be cheap enough to entice people to actually use them. In the world of at-home diagnostics, pregnancy tests have become the sole mainstream victor because they're simple to use, small to carry, easy to interpret, and costs about seven or eight dollars at any ubiquitous store, like Target or Walmart. By comparison, the at-home COVID collection tests that don't even offer diagnostics—you send away your sample to an external lab—all cost over $100 to take just one time.
For the time being, the only available diagnostics for COVID require a lab or an expensive dedicated machine to process. This disconnect could prolong the world's worst health crisis in a century.
"Daily rapid tests have enormous potential to sever transmission chains and create herd effects similar to herd immunity," Mina says. "We all recognize that vaccines and infections can result in herd immunity when something around half of people are no longer susceptible.
"The same thing exists with these tests. These are the intervention to stop the virus. If half of people choose to use these tests every other day, then we can stop transmission faster than a vaccine can. The technology exists, the theory and mathematics back it up, the epidemiology is sound. There is no reason we are not approaching this as strongly as we would be approaching vaccines."
--Additional reporting by Julia Sklar
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
After spaceflight record, NASA looks to protect astronauts on even longer trips
At T-minus six seconds, the main engines of the Atlantis Space Shuttle ignited, rattling its capsule “like a skyscraper in an earthquake,” according to astronaut Tom Jones, describing the 1988 launch. As the rocket lifted off and accelerated to three times the force of Earth's gravity, “It felt as if two of my friends were standing on my chest and wouldn’t get off.” But when Atlantis reached orbit, the main engines cut off, and the astronauts were suddenly weightless.
Since 1961, NASA has sent hundreds of astronauts into space while working to making their voyages safer and smoother. Yet, challenges remain. Weightlessness may look amusing when watched from Earth, but it has myriad effects on cognition, movement and other functions. When missions to space stretch to six months or longer, microgravity can impact astronauts’ health and performance, making it more difficult to operate their spacecraft.
Yesterday, NASA astronaut Frank Rubio returned to Earth after over one year, the longest single spaceflight for a U.S. astronaut. But this is just the start; longer and more complex missions into deep space loom ahead, from returning to the moon in 2025 to eventually sending humans to Mars. To ensure that these missions succeed, NASA is increasing efforts to study the biological effects and prevent harm.
The dangers of microgravity are real
A NASA report published in 2016 details a long list of incidents and near-misses caused – at least partly – by space-induced changes in astronauts’ vision and coordination. These issues make it harder to move with precision and to judge distance and velocity.
According to the report, in 1997, a resupply ship collided with the Mir space station, possibly because a crew member bumped into the commander during the final docking maneuver. This mishap caused significant damage to the space station.
Returns to Earth suffered from problems, too. The same report notes that touchdown speeds during the first 100 space shuttle landings were “outside acceptable limits. The fastest landing on record – 224 knots (258 miles) per hour – was linked to the commander’s momentary spatial disorientation.” Earlier, each of the six Apollo crews that landed on the moon had difficulty recognizing moon landmarks and estimating distances. For example, Apollo 15 landed in an unplanned area, ultimately straddling the rim of a five-foot deep crater on the moon, harming one of its engines.
Spaceflight causes unique stresses on astronauts’ brains and central nervous systems. NASA is working to reduce these harmful effects.
NASA
Space messes up your brain
In space, astronauts face the challenges of microgravity, ionizing radiation, social isolation, high workloads, altered circadian rhythms, monotony, confined living quarters and a high-risk environment. Among these issues, microgravity is one of the most consequential in terms of physiological changes. It changes the brain’s structure and its functioning, which can hurt astronauts’ performance.
The brain shifts upwards within the skull, displacing the cerebrospinal fluid, which reduces the brain’s cushioning. Essentially, the brain becomes crowded inside the skull like a pair of too-tight shoes.
That’s partly because of how being in space alters blood flow. On Earth, gravity pulls our blood and other internal fluids toward our feet, but our circulatory valves ensure that the fluids are evenly distributed throughout the body. In space, there’s not enough gravity to pull the fluids down, and they shift up, says Rachael D. Seidler, a physiologist specializing in spaceflight at the University of Florida and principal investigator on many space-related studies. The head swells and legs appear thinner, causing what astronauts call “puffy face chicken legs.”
“The brain changes at the structural and functional level,” says Steven Jillings, equilibrium and aerospace researcher at the University of Antwerp in Belgium. “The brain shifts upwards within the skull,” displacing the cerebrospinal fluid, which reduces the brain’s cushioning. Essentially, the brain becomes crowded inside the skull like a pair of too-tight shoes. Some of the displaced cerebrospinal fluid goes into cavities within the brain, called ventricles, enlarging them. “The remaining fluids pool near the chest and heart,” explains Jillings. After 12 consecutive months in space, one astronaut had a ventricle that was 25 percent larger than before the mission.
Some changes reverse themselves while others persist for a while. An example of a longer-lasting problem is spaceflight-induced neuro-ocular syndrome, which results in near-sightedness and pressure inside the skull. A study of approximately 300 astronauts shows near-sightedness affects about 60 percent of astronauts after long missions on the International Space Station (ISS) and more than 25 percent after spaceflights of only a few weeks.
Another long-term change could be the decreased ability of cerebrospinal fluid to clear waste products from the brain, Seidler says. That’s because compressing the brain also compresses its waste-removing glymphatic pathways, resulting in inflammation, vulnerability to injuries and worsening its overall health.
The effects of long space missions were best demonstrated on astronaut twins Scott and Mark Kelly. This NASA Twins Study showed multiple, perhaps permanent, changes in Scott after his 340-day mission aboard the ISS, compared to Mark, who remained on Earth. The differences included declines in Scott’s speed, accuracy and cognitive abilities that persisted longer than six months after returning to Earth in March 2016.
By the end of 2020, Scott’s cognitive abilities improved, but structural and physiological changes to his eyes still remained, he said in a BBC interview.
“It seems clear that the upward shift of the brain and compression of the surrounding tissues with ventricular expansion might not be a good thing,” Seidler says. “But, at this point, the long-term consequences to brain health and human performance are not really known.”
NASA astronaut Kate Rubins conducts a session for the Neuromapping investigation.
NASA
Staying sharp in space
To investigate how prolonged space travel affects the brain, NASA launched a new initiative called the Complement of Integrated Protocols for Human Exploration Research (CIPHER). “CIPHER investigates how long-duration spaceflight affects both brain structure and function,” says neurobehavioral scientist Mathias Basner at the University of Pennsylvania, a principal investigator for several NASA studies. “Through it, we can find out how the brain adapts to the spaceflight environment and how certain brain regions (behave) differently after – relative to before – the mission.”
To do this, he says, “Astronauts will perform NASA’s cognition test battery before, during and after six- to 12-month missions, and will also perform the same test battery in an MRI scanner before and after the mission. We have to make sure we better understand the functional consequences of spaceflight on the human brain before we can send humans safely to the moon and, especially, to Mars.”
As we go deeper into space, astronauts cognitive and physical functions will be even more important. “A trip to Mars will take about one year…and will introduce long communication delays,” Seidler says. “If you are on that mission and have a problem, it may take eight to 10 minutes for your message to reach mission control, and another eight to 10 minutes for the response to get back to you.” In an emergency situation, that may be too late for the response to matter.
“On a mission to Mars, astronauts will be exposed to stressors for unprecedented amounts of time,” Basner says. To counter them, NASA is considering the continuous use of artificial gravity during the journey, and Seidler is studying whether artificial gravity can reduce the harmful effects of microgravity. Some scientists are looking at precision brain stimulation as a way to improve memory and reduce anxiety due to prolonged exposure to radiation in space.
Other scientists are exploring how to protect neural stem cells (which create brain cells) from radiation damage, developing drugs to repair damaged brain cells and protect cells from radiation.
To boldly go where no astronauts have gone before, they must have optimal reflexes, vision and decision-making. In the era of deep space exploration, the brain—without a doubt—is the final frontier.
Additionally, NASA is scrutinizing each aspect of the mission, including astronaut exercise, nutrition and intellectual engagement. “We need to give astronauts meaningful work. We need to stimulate their sensory, cognitive and other systems appropriately,” Basner says, especially given their extreme confinement and isolation. The scientific experiments performed on the ISS – like studying how microgravity affects the ability of tissue to regenerate is a good example.
“We need to keep them engaged socially, too,” he continues. The ISS crew, for example, regularly broadcasts from space and answers prerecorded questions from students on Earth, and can engage with social media in real time. And, despite tight quarters, NASA is ensuring the crew capsule and living quarters on the moon or Mars include private space, which is critical for good mental health.
Exploring deep space builds on a foundation that began when astronauts first left the planet. With each mission, scientists learn more about spaceflight effects on astronauts’ bodies. NASA will be using these lessons to succeed with its plans to build science stations on the moon and, eventually, Mars.
“Through internally and externally led research, investigations implemented in space and in spaceflight simulations on Earth, we are striving to reduce the likelihood and potential impacts of neurostructural changes in future, extended spaceflight,” summarizes NASA scientist Alexandra Whitmire. To boldly go where no astronauts have gone before, they must have optimal reflexes, vision and decision-making. In the era of deep space exploration, the brain—without a doubt—is the final frontier.
A newly discovered brain cell may lead to better treatments for cognitive disorders
Swiss researchers have discovered a third type of brain cell that appears to be a hybrid of the two other primary types — and it could lead to new treatments for many brain disorders.
The challenge: Most of the cells in the brain are either neurons or glial cells. While neurons use electrical and chemical signals to send messages to one another across small gaps called synapses, glial cells exist to support and protect neurons.
Astrocytes are a type of glial cell found near synapses. This close proximity to the place where brain signals are sent and received has led researchers to suspect that astrocytes might play an active role in the transmission of information inside the brain — a.k.a. “neurotransmission” — but no one has been able to prove the theory.
A new brain cell: Researchers at the Wyss Center for Bio and Neuroengineering and the University of Lausanne believe they’ve definitively proven that some astrocytes do actively participate in neurotransmission, making them a sort of hybrid of neurons and glial cells.
According to the researchers, this third type of brain cell, which they call a “glutamatergic astrocyte,” could offer a way to treat Alzheimer’s, Parkinson’s, and other disorders of the nervous system.
“Its discovery opens up immense research prospects,” said study co-director Andrea Volterra.
The study: Neurotransmission starts with a neuron releasing a chemical called a neurotransmitter, so the first thing the researchers did in their study was look at whether astrocytes can release the main neurotransmitter used by neurons: glutamate.
By analyzing astrocytes taken from the brains of mice, they discovered that certain astrocytes in the brain’s hippocampus did include the “molecular machinery” needed to excrete glutamate. They found evidence of the same machinery when they looked at datasets of human glial cells.
Finally, to demonstrate that these hybrid cells are actually playing a role in brain signaling, the researchers suppressed their ability to secrete glutamate in the brains of mice. This caused the rodents to experience memory problems.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Andrea Volterra, University of Lausanne.
But why? The researchers aren’t sure why the brain needs glutamatergic astrocytes when it already has neurons, but Volterra suspects the hybrid brain cells may help with the distribution of signals — a single astrocyte can be in contact with thousands of synapses.
“Often, we have neuronal information that needs to spread to larger ensembles, and neurons are not very good for the coordination of this,” researcher Ludovic Telley told New Scientist.
Looking ahead: More research is needed to see how the new brain cell functions in people, but the discovery that it plays a role in memory in mice suggests it might be a worthwhile target for Alzheimer’s disease treatments.
The researchers also found evidence during their study that the cell might play a role in brain circuits linked to seizures and voluntary movements, meaning it’s also a new lead in the hunt for better epilepsy and Parkinson’s treatments.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Volterra.