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.
If you look back on the last century of scientific achievements, you might notice that most of the scientists we celebrate are overwhelmingly white, while scientists of color take a backseat. Since the Nobel Prize was introduced in 1901, for example, no black scientists have landed this prestigious award.
The work of black women scientists has gone unrecognized in particular. Their work uncredited and often stolen, black women have nevertheless contributed to some of the most important advancements of the last 100 years, from the polio vaccine to GPS.
Here are five black women who have changed science forever.
Dr. May Edward Chinn
Dr. May Edward Chinn practicing medicine in Harlem
George B. Davis, PhD.
Chinn was born to poor parents in New York City just before the start of the 20th century. Although she showed great promise as a pianist, playing with the legendary musician Paul Robeson throughout the 1920s, she decided to study medicine instead. Chinn, like other black doctors of the time, were barred from studying or practicing in New York hospitals. So Chinn formed a private practice and made house calls, sometimes operating in patients’ living rooms, using an ironing board as a makeshift operating table.
Chinn worked among the city’s poor, and in doing this, started to notice her patients had late-stage cancers that often had gone undetected or untreated for years. To learn more about cancer and its prevention, Chinn begged information off white doctors who were willing to share with her, and even accompanied her patients to other clinic appointments in the city, claiming to be the family physician. Chinn took this information and integrated it into her own practice, creating guidelines for early cancer detection that were revolutionary at the time—for instance, checking patient health histories, checking family histories, performing routine pap smears, and screening patients for cancer even before they showed symptoms. For years, Chinn was the only black female doctor working in Harlem, and she continued to work closely with the poor and advocate for early cancer screenings until she retired at age 81.
Alice Ball
Pictorial Press Ltd/Alamy
Alice Ball was a chemist best known for her groundbreaking work on the development of the “Ball Method,” the first successful treatment for those suffering from leprosy during the early 20th century.
In 1916, while she was an undergraduate student at the University of Hawaii, Ball studied the effects of Chaulmoogra oil in treating leprosy. This oil was a well-established therapy in Asian countries, but it had such a foul taste and led to such unpleasant side effects that many patients refused to take it.
So Ball developed a method to isolate and extract the active compounds from Chaulmoogra oil to create an injectable medicine. This marked a significant breakthrough in leprosy treatment and became the standard of care for several decades afterward.
Unfortunately, Ball died before she could publish her results, and credit for this discovery was given to another scientist. One of her colleagues, however, was able to properly credit her in a publication in 1922.
Henrietta Lacks
onathan Newton/The Washington Post/Getty
The person who arguably contributed the most to scientific research in the last century, surprisingly, wasn’t even a scientist. Henrietta Lacks was a tobacco farmer and mother of five children who lived in Maryland during the 1940s. In 1951, Lacks visited Johns Hopkins Hospital where doctors found a cancerous tumor on her cervix. Before treating the tumor, the doctor who examined Lacks clipped two small samples of tissue from Lacks’ cervix without her knowledge or consent—something unthinkable today thanks to informed consent practices, but commonplace back then.
As Lacks underwent treatment for her cancer, her tissue samples made their way to the desk of George Otto Gey, a cancer researcher at Johns Hopkins. He noticed that unlike the other cell cultures that came into his lab, Lacks’ cells grew and multiplied instead of dying out. Lacks’ cells were “immortal,” meaning that because of a genetic defect, they were able to reproduce indefinitely as long as certain conditions were kept stable inside the lab.
Gey started shipping Lacks’ cells to other researchers across the globe, and scientists were thrilled to have an unlimited amount of sturdy human cells with which to experiment. Long after Lacks died of cervical cancer in 1951, her cells continued to multiply and scientists continued to use them to develop cancer treatments, to learn more about HIV/AIDS, to pioneer fertility treatments like in vitro fertilization, and to develop the polio vaccine. To this day, Lacks’ cells have saved an estimated 10 million lives, and her family is beginning to get the compensation and recognition that Henrietta deserved.
Dr. Gladys West
Andre West
Gladys West was a mathematician who helped invent something nearly everyone uses today. West started her career in the 1950s at the Naval Surface Warfare Center Dahlgren Division in Virginia, and took data from satellites to create a mathematical model of the Earth’s shape and gravitational field. This important work would lay the groundwork for the technology that would later become the Global Positioning System, or GPS. West’s work was not widely recognized until she was honored by the US Air Force in 2018.
Dr. Kizzmekia "Kizzy" Corbett
TIME Magazine
At just 35 years old, immunologist Kizzmekia “Kizzy” Corbett has already made history. A viral immunologist by training, Corbett studied coronaviruses at the National Institutes of Health (NIH) and researched possible vaccines for coronaviruses such as SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome).
At the start of the COVID pandemic, Corbett and her team at the NIH partnered with pharmaceutical giant Moderna to develop an mRNA-based vaccine against the virus. Corbett’s previous work with mRNA and coronaviruses was vital in developing the vaccine, which became one of the first to be authorized for emergency use in the United States. The vaccine, along with others, is responsible for saving an estimated 14 million lives.On today’s episode of Making Sense of Science, I’m honored to be joined by Dr. Paul Song, a physician, oncologist, progressive activist and biotech chief medical officer. Through his company, NKGen Biotech, Dr. Song is leveraging the power of patients’ own immune systems by supercharging the body’s natural killer cells to make new treatments for Alzheimer’s and cancer.
Whereas other treatments for Alzheimer’s focus directly on reducing the build-up of proteins in the brain such as amyloid and tau in patients will mild cognitive impairment, NKGen is seeking to help patients that much of the rest of the medical community has written off as hopeless cases, those with late stage Alzheimer’s. And in small studies, NKGen has shown remarkable results, even improvement in the symptoms of people with these very progressed forms of Alzheimer’s, above and beyond slowing down the disease.
In the realm of cancer, Dr. Song is similarly setting his sights on another group of patients for whom treatment options are few and far between: people with solid tumors. Whereas some gradual progress has been made in treating blood cancers such as certain leukemias in past few decades, solid tumors have been even more of a challenge. But Dr. Song’s approach of using natural killer cells to treat solid tumors is promising. You may have heard of CAR-T, which uses genetic engineering to introduce cells into the body that have a particular function to help treat a disease. NKGen focuses on other means to enhance the 40 plus receptors of natural killer cells, making them more receptive and sensitive to picking out cancer cells.
Paul Y. Song, MD is currently CEO and Vice Chairman of NKGen Biotech. Dr. Song’s last clinical role was Asst. Professor at the Samuel Oschin Cancer Center at Cedars Sinai Medical Center.
Dr. Song served as the very first visiting fellow on healthcare policy in the California Department of Insurance in 2013. He is currently on the advisory board of the Pritzker School of Molecular Engineering at the University of Chicago and a board member of Mercy Corps, The Center for Health and Democracy, and Gideon’s Promise.
Dr. Song graduated with honors from the University of Chicago and received his MD from George Washington University. He completed his residency in radiation oncology at the University of Chicago where he served as Chief Resident and did a brachytherapy fellowship at the Institute Gustave Roussy in Villejuif, France. He was also awarded an ASTRO research fellowship in 1995 for his research in radiation inducible gene therapy.
With Dr. Song’s leadership, NKGen Biotech’s work on natural killer cells represents cutting-edge science leading to key findings and important pieces of the puzzle for treating two of humanity’s most intractable diseases.
Show links
- Paul Song LinkedIn
- NKGen Biotech on Twitter - @NKGenBiotech
- NKGen Website: https://nkgenbiotech.com/
- NKGen appoints Paul Song
- Patient Story: https://pix11.com/news/local-news/long-island/promising-new-treatment-for-advanced-alzheimers-patients/
- FDA Clearance: https://nkgenbiotech.com/nkgen-biotech-receives-ind-clearance-from-fda-for-snk02-allogeneic-natural-killer-cell-therapy-for-solid-tumors/Q3 earnings data: https://www.nasdaq.com/press-release/nkgen-biotech-inc.-reports-third-quarter-2023-financial-results-and-business