COVID-19 testing
RADx Initiative: Bioengineering for COVID-19 at Unprecedented Speed and Scale
Posted on by Bruce J. Tromberg, Ph.D., National Institute of Biomedical Imaging and Bioengineering
As COVID-19 rapidly expanded throughout the world in April 2020, many in the biomedical technology community voiced significant concerns about the lack of available diagnostic tests. At that time, testing for SARS-CoV-2, the coronavirus that causes COVID-19, was conducted exclusively in clinical laboratories by order of a health-care provider. “Over the counter” (OTC) tests did not exist, and low complexity point of care (POC) platforms were rare. Fewer than 8 million tests were performed in the U.S. that month, and it was clear that we needed a radical transformation to make tests faster and more accessible.
By February 2022, driven by the Omicron variant surge, U.S. capacity had increased to a new record of more than 1.2 billion tests in a single month. Remarkably, the overwhelming majority of these—more than 85 percent—were “rapid tests” conducted in home and POC settings.
The story behind this practice-changing, “test-at-home” transformation is deeply rooted in technologic and manufacturing innovation. The NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB), working collaboratively with multiple partners across NIH, government, academia, and the private sector, has been privileged to play a leading role in this effort via the Rapid Acceleration of Diagnostics (RADx®) initiative. On this two-year anniversary of RADx, we take a brief look back at its formation, impact, and potential for future growth.
On April 24, 2020, Congress recognized that testing was an urgent national need and appropriated $1.5 billion to NIH via an emergency supplement [1]. The goal was to substantially increase the number, type, and availability of diagnostic tests in only five to six months. Since the “normal” commercialization cycle for this type of diagnostic technology is typically more than five years, we needed an entirely new approach . . . fast.
The RADx initiative was launched just five days after that challenging Congressional directive [2]. Four NIH RADx programs were eventually created to support technology development and delivery, with the goal of matching test performance with community needs [3].The first two programs, RADx Tech and RADx Advanced Technology Platforms (ATP), were developed by NIBIB and focused on innovation for rapidly creating, scaling up, and deploying new technologies.
RADx Tech is built around NIBIB’s Point of Care Technologies Research Network (POCTRN) and includes core activities for technology review, test validation, clinical studies, regulatory authorization, and test deployment. Overall, the RADx Tech network includes approximately 900 participants from government, academia, and the private sector with unique capabilities and resources designed to decrease inherent risk and guide technologies from design and development to fully disseminated commercial products.
At the core of RADx Tech operations is the “innovation funnel” rapid review process, popularized as a shark tank [4]. A total of 824 complete applications were submitted during two open calls in a four-month period, beginning April 2020 and during a one-month period in June 2021. Forty-seven projects received phase 1 funding to validate and lower the inherent risk of developing these technologies. Meanwhile, 50 companies received phase 2 contracts to support FDA authorization studies and manufacturing expansion [5]
Beyond test development, RADx Tech has evolved to become a key contributor to the U.S. COVID-19 response. The RADx Independent Test Assessment Program (ITAP) was launched in October 2021 to accelerate regulatory authorization of new tests as a joint effort with the Food and Drug Administration (FDA) [6]. The ITAP acquires analytical and clinical performance data and works closely with FDA and manufacturers to shave weeks to months off the time it normally takes to receive Emergency Use Authorization (EUA).
The RADx Tech program also created a Variant Task Force to monitor the performance of tests against each new coronavirus “variant of concern” that emerges. This helps to ensure that marketed tests continue to remain effective. Other innovative RADx Tech projects include Say Yes! Covid Test, the first online free OTC test distribution program, and Project Rosa, which conducts real-time variant tracking across the country [7].
RADx Tech, by any measure, has exceeded even the most-optimistic expectations. In two years, RADx Tech-supported companies have received 44 EUAs and added approximately 2 billion tests and test products to the U.S. capacity. These remarkable numbers have steadily increased from more than16 million tests in September 2020, just five months after the program was established [8].
RADx Tech has also made significant contributions to the distribution of 1 billion free OTC tests via the government site, COVID.gov/tests. It has also provided critical guidance on serial testing and variants that have improved test performance and changed regulatory practice [9,10]. In addition, the RADx Mobile Application Reporting System (RADx MARS) reduces barriers to test reporting and test-to-treat strategies’ The latter offers immediate treatment options via telehealth or a POC location whenever a positive test result is reported. Finally, the When to Test website provides critical guidance on when and how to test for individuals, groups, and communities.
As we look to the future, RADx Tech has enormous potential to impact the U.S. response to other pathogens, diseases, and future pandemics. Major challenges going forward include improving home tests to work as well as lab platforms and building digital health networks for capturing and reporting test results to public health officials [11].
A recent editorial published in the journal Nature Biotechnology noted, “RADx has spawned a phalanx of diagnostic products to market in just 12 months. Its long-term impact on point of care, at-home, and population testing may be even more profound [12].” We are now poised to advance a new wave of precision medicine that’s led by innovative diagnostic technologies. It represents a unique opportunity to emerge stronger from the pandemic and achieve long-term impact.
References:
[1] Public Law 116 -139—Paycheck Protection Program and Health Care Enhancement Act.
[2] NIH mobilizes national innovation initiative for COVID-19 diagnostics, NIH news release, April 29, 2020.
[3] Rapid scaling up of Covid-19 diagnostic testing in the United States—The NIH RADx Initiative. Tromberg BJ, Schwetz TA, Pérez-Stable EJ, Hodes RJ, Woychik RP, Bright RA, Fleurence RL, Collins FS. N Engl J Med. 2020 Sep 10;383(11):1071-1077.
[4] We need more covid-19 tests. We propose a ‘shark tank’ to get us there. Alexander L. and Blunt R., Washington Post, April 20, 2020.
[5] RADx® Tech/ATP dashboard, National Institute of Biomedical Imaging and Bioengineering, NIH.
[6] New HHS actions add to Biden Administration efforts to increase access to easy-to-use over-the-counter COVID-19 tests. U.S. Department of Health and Human Services Press Office, October 25, 2021.
[7] A method for variant agnostic detection of SARS-CoV-2, rapid monitoring of circulating variants, detection of mutations of biological significance, and early detection of emergent variants such as Omicron. Lai E, et al. medRxiV preprint, January 9, 2022.
[9] Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection. Smith RL, et al. J Infect Dis. 2021 Sep 17;224(6):976-982.
[10] Comparison of rapid antigen tests’ performance between Delta (B.1.61.7; AY.X) and Omicron (B.1.1.529; BA1) variants of SARS-CoV-2: Secondary analysis from a serial home self-testing study. Soni A, et al. MedRxiv preprint, March 2, 2022.
[11] Reporting COVID-19 self-test results: The next frontier. Health Affairs, Juluru K., et al. Health Affairs, February 11, 2022.
[12] Radical solutions. Nat Biotechnol. 2021 Apr;39(4):391.
Links:
Get Free At-Home COVID Tests (COVID.gov)
When to Test (Consortia for Improving Medicine with Innovation & Technology, Boston)
RADx Programs (NIH)
RADx® Tech and ATP Programs (National Institute of Biomedical Imaging and Biomedical Engineering/NIH)
Independent Test Assessment Program (NIBIB)
Mobile Application Reporting through Standards (NIBIB)
Point-of-Care Technologies Research Network (POCTRN) (NIBIB)
[Note: Acting NIH Director Lawrence Tabak has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the eighth in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.]
Learning to Protect Communities with COVID-19 Home Testing Programs
Posted on by Dr. Francis Collins
With most kids now back in school, parents face a new everyday concern: determining whether their child’s latest cough or sneeze might be a sign of COVID-19. If so, parents will want to keep their child at home to protect other students and staff, while also preventing the spread of the virus in their communities. And if it’s the parent who has a new cough, they also will want to know if the reason is COVID-19 before going to work or the store.
Home tests are now coming online to help concerned people make the right choice quickly. As more COVID-19 home tests enter the U.S. marketplace, research continues to help optimize their use. That’s why NIH and the Centers for Disease Control and Prevention (CDC) are teaming up in several parts of the country to provide residents age 2 and older with free home-testing kits for COVID-19. These reliable, nasal swab tests provide yes-or-no answers in about 15 minutes for parents and anyone else concerned about their possible exposure to the novel coronavirus.
The tests are part of an initiative called Say Yes! COVID Test (SYCT) that’s evaluating how best to implement home-testing programs within range of American communities, both urban and rural. The lessons learned are providing needed science-based data to help guide public health officials who are interested in implementing similar home-testing programs in communities throughout their states.
After successful eight-week pilot programs this past spring and summer in parts of North Carolina, Tennessee, and Michigan, SYCT is partnering this fall with four new communities. They are Fulton County, GA; Honolulu County, HI; Louisville Metro, KY; and Marion County, IN.
The Georgia and Hawaii partnerships, launched on September 20, are already off to a flying start. In Fulton County, home to Atlanta and several small cities, 21,673 direct-to-consumer orders (173,384 tests) have already been received. In Honolulu County, demand for the tests has exceeded all expectations, with 91,000 orders received in the first week (728,000 tests). The online ordering has now closed in Hawaii, and the remaining tests will be distributed on the ground through the local public health department.
SYCT offers the Quidel QuickVue® At-Home COVID-19 test, which is supplied through the NIH Rapid Acceleration of Diagnostics (RADx) initiative. The antigen test uses a self-collected nasal swab sample that is placed in a test tube containing solution, followed by a test strip. Colored lines that appear on the test strip indicate a positive or negative result—similar to a pregnancy test.
The program allows residents in participating counties to order free home tests online or for in-person pick up at designated sites in their community. Each resident can ask for eight rapid tests, which equals two weekly tests over four weeks. An easy-to-navigate website like this one and a digital app, developed by initiative partner CareEvolution, are available for residents to order their tests, sign-up for testing reminders, and allow voluntary test result reporting to the public health department.
SYCT will generate data to answer several important questions about self or home-testing. They include questions about consumer demand, ensuring full community access, testing behavior, willingness to report test results, and, above all, effectiveness in controlling the spread of SARS-CoV-2, the coronavirus that causes COVID-19
Researchers at the University of North Carolina-Chapel Hill; Duke University, Durham, NC; and the UMass Chan Medical School, Worcester, MA, will help crunch the data and look for guiding themes. They will also conduct a study pre- and post-intervention to evaluate levels of SARS-CoV-2 in the community, including using measures of virus in wastewater. In addition, researchers will compare their results to other counties similar in size and infection rates, but that are not participating in a free testing initiative.
The NIH and CDC are exploring ways to scale a SYCT-like program nationally to communities experiencing surges in COVID-19. The Biden Administration also recently invoked the Defense Production Act to purchase millions of COVID-19 home tests to help accelerate their availability and offer them at a lower cost to more Americans. That encompasses many different types of people, including concerned parents who need a quick-and-accurate answer on whether their children’s cough or sneeze is COVID-19.
Links:
COVID-19 Research (NIH)
Rapid Acceleration of Diagnostics (RADx) (NIH)
NIH Support: National Institute of Biomedical Imaging and Bioengineering; National Heart, Lung, and Blood Institute; National Institute on Minority Health and Health Disparities
COVID-19 Infected Many More Americans in 2020 than Official Tallies Show
Posted on by Dr. Francis Collins
At the end of last year, you may recall hearing news reports that the number of COVID-19 cases in the United States had topped 20 million. While that number came as truly sobering news, it also likely was an underestimate. Many cases went undetected due to limited testing early in the year and a large number of infections that produced mild or no symptoms.
Now, a recent article published in Nature offers a more-comprehensive estimate that puts the true number of infections by the end of 2020 at more than 100 million [1]. That’s equal to just under a third of the U.S. population of 328 million. This revised number shows just how rapidly this novel coronavirus spread through the country last year. It also brings home just how timely the vaccines have been—and continue to be in 2021—to protect our nation’s health in this time of pandemic.
The work comes from NIH grantee Jeffrey Shaman, Sen Pei, and colleagues, Columbia University, New York. As shown above in the map, the researchers estimated the percentage of people who had been infected with SARS-CoV-2, the novel coronavirus that causes COVID-19, in communities across the country through December 2020.
To generate this map, they started with existing national data on the number of coronavirus cases (both detected and undetected) in 3,142 U.S. counties and major metropolitan areas. They then factored in data from the Centers for Disease Control and Prevention (CDC) on the number of people who tested positive for antibodies against SARS-CoV-2. These CDC data are useful for picking up on past infections, including those that went undetected.
From these data, the researchers calculated that only about 11 percent of all COVID-19 cases were confirmed by a positive test result in March 2020. By the end of the year, with testing improvements and heightened public awareness of COVID-19, the ascertainment rate (the number of infections that were known versus unknown) rose to about 25 percent on average. This measure also varied a lot across the country. For instance, the ascertainment rates in Miami and Phoenix were higher than the national average, while rates in New York City, Los Angeles, and Chicago were lower than average.
How many people were potentially walking around with a contagious SARS-CoV-2 infection? The model helps to answer this, too. On December 31, 2020, the researchers estimate that 0.77 percent of the U.S. population had a contagious infection. That’s about 1 in every 130 people on average. In some places, it was much higher. In Los Angeles, for example, nearly 1 in 40 (or 2.42 percent) had a SARS-CoV-2 infection as they rang in the New Year.
Over the course of the year, the fatality rate associated with COVID-19 dropped, at least in part due to earlier diagnosis and advances in treatment. The fatality rate went from 0.77 percent in April to 0.31 percent in December. While this is great news, it still shows that COVID-19 remains much more dangerous than seasonal influenza (which has a fatality rate of 0.08 percent).
Today, the landscape has changed considerably. Vaccines are now widely available, giving many more people immune protection without ever having to get infected. And yet, the rise of the Delta and other variants means that breakthrough infections and reinfections—which the researchers didn’t account for in their model—have become a much bigger concern.
Looking ahead to the end of 2021, Americans must continue to do everything they can to protect their communities from the spread of this terrible virus. That means getting vaccinated if you haven’t already, staying home and getting tested if you’ve got symptoms or know of an exposure, and taking other measures to keep yourself and your loved ones safe and well. These measures we take now will influence the infection rates and susceptibility to SARS-CoV-2 in our communities going forward. That will determine what the map of SARS-CoV-2 infections will look like in 2021 and beyond and, ultimately, how soon we can finally put this pandemic behind us.
Reference:
[1] Burden and characteristics of COVID-19 in the United States during 2020. Pei S, Yamana TK, Kandula S, Galanti M, Shaman J. Nature. 2021 Aug 26.
Links:
COVID-19 Research (NIH)
Sen Pei (Columbia University, New York)
Jeffrey Shaman (Columbia University, New York)
New Metric Identifies Coronavirus Hotspots in Real Time
Posted on by Dr. Francis Collins
During the pandemic, it’s been critical to track in real time where the coronavirus is spreading at home and abroad. But it’s often hard for public health officials to know whether changes in the reported number of COVID-19 cases over time truly reflect the spread of the virus or whether they are confounded by changes in testing levels or lags in the reporting of results.
Now, NIH-funded researchers have discovered a clever workaround to detect more accurately where COVID-19 hotspots are emerging. As published in the journal Science, the new approach focuses on the actual amount of virus present in a positive COVID diagnostic test [1], not just whether the test is positive or negative. What’s even better is these data on a person’s “viral load” are readily available from polymerase chain reaction, or PCR, tests that are the “gold standard” for detecting SARS-CoV-2, the virus responsible for COVID-19. In fact, if you’ve been tested for COVID-19, there’s a good chance you’ve had a PCR-based test.
Here’s how a PCR test for COVID-19 works. After a person provides a nasal swab or saliva sample, any genetic material in the sample is extracted and prepared for the PCR machine. It uses special nucleic acid primers that, if any genetic material from SARS-CoV-2 is present, will make millions more copies of them and result in a positive test result. PCR is an enzymatic reaction that works by running many cycles of heating and cooling; each cycle results in doubling of the genetic material present in the original sample.
But it turns out that PCR can go beyond a simple “yes” or “no” test result. It’s also possible to get some sense of how much coronavirus is present in a positive sample based on the number of cycles required to make enough copies of its genetic material to get the “yes” result. This measure is known as the “cycle threshold,” or Ct, value.
When a sample is run with lots of virus in it, the PCR machine doesn’t need to make so many cycles to reach detectable levels—and the Ct value is considered low. But, when the virus is barely present in a sample, the machine needs to run more cycles before it will reach the threshold for detection. In this case, the Ct value is high. This makes the Ct metric a bit counterintuitive: low Ct means a high level of infection, and high Ct means a low level of infection.
In the new study, researchers in Michael Mina’s lab, Harvard T. H. Chan School of Public Health, Boston, including James Hay and Lee Kennedy-Shaffer, wanted to use Ct values to understand better the overall trajectory of the spread of SARS-CoV-2. Their idea was a little out of the box, since Ct values weren’t being factored into a diagnostic testing process that was set up to give people a yes-or-no answer about COVID-19 status. In fact, Ct values were often discarded.
The team members had a hunch that the amount of virus in patient samples would vary based on whether an outbreak is increasing or declining. Their reasoning was that during an outbreak, when SARS-CoV-2 is spreading rapidly through a community, a larger proportion of infected individuals will have recently contracted the virus than when it is spreading more slowly. The researchers also knew that the virus reaches its peak level in humans soon after infection (generally a couple of days before symptoms begin), and then falls to very low but still detectable levels over the course of weeks or sometimes even months. So, when viral load within samples is highest—and Ct values are lowest—it suggests an outbreak of SARS-CoV-2 is underway. As an outbreak slows and cases fall, viral loads should fall and Ct values rise.
The researchers found that just 30 positive PCR test results on a single day were enough to give an accurate real-time estimate of the growth rate of SARS-CoV-2 infections based on Ct values. With Ct values from multiple time points, it was possible to reconstruct the epidemic curve and estimate the true number of people infected. They found that even Ct values collected from a single location at a single point in time could provide extremely valuable information about the growth or decline of an outbreak.
The findings suggest that these data can now be captured and put to good use as a key metric for decision-making and gauging the success of the pandemic response going forward. It’s also important to note that the value of these data are not unique to COVID-19 and the ongoing pandemic. It appears this can be extremely useful new way to monitor the course of other viral outbreaks, now and in the future, in a way that’s less susceptible to the vagaries of testing. The hope is that this will mean even greater success in capturing viral outbreaks and mobilizing resources in real time to the places where they are most needed.
Reference:
[1] Estimating epidemiologic dynamics from cross-sectional viral load distributions. Hay JA, Kennedy-Shaffer L, Kanjilal S, Lennon NJ, Gabriel SB, Lipsitch M, Mina MJ. Science. 2021 Jun 3.
Links:
COVID-19 Research (NIH)
Michael Mina (Harvard T. H. Chan School of Public Health, Boston)
NIH Support: Common Fund, National Institute of General Medical Sciences; National Cancer Institute
New Initiative Puts At-Home Testing to Work in the Fight Against COVID-19
Posted on by Dr. Francis Collins
Thankfully COVID-19 testing is now more widely available than it was earlier in the pandemic. But getting tested often still involves going to a doctor’s office or community testing site and waiting as long as a couple of days for the results. Testing would be so much easier if people could do it themselves at home. If the result came up positive, a person could immediately self-isolate, helping to stop the coronavirus that causes COVID-19, SARS-CoV-2, from spreading any further in their communities.
That’s why I’m happy to report that the Centers for Disease Control and Prevention (CDC), in close collaboration with state and local public health departments and with NIH, has begun an innovative community health initiative called “Say Yes! COVID Test.” The initiative, the first large-scale evaluation of community-wide, self-administered COVID-19 testing, was launched last week in Pitt County, NC, and will start soon in Chattanooga/Hamilton County, TN.
The initiative will provide as many as 160,000 residents in these two locales with free access to rapid COVID-19 home tests, supplied through NIH’s Rapid Acceleration of Diagnostics (RADx) initiative. Participants can administer these easy-to-use tests themselves up to three times a week for one month. The goal is to assess the benefits of self-administered COVID-19 testing and help guide other communities in implementing similar future programs to slow the spread of COVID-19.
The counties in North Carolina and Tennessee were selected based on several criteria. These included local infection rates; public availability of accurate COVID-19 tracking data, such as that gathered by wastewater surveillance; the presence of local infrastructure needed to support the project; and existing community relationships through RADx’s Underserved Populations (RADx-UP) program. Taken together, these criteria also help to ensure that vulnerable and underserved populations will benefit from the initiative.
The test is called the QuickVue At-Home COVID-19 Test. Developed with RADx support by San Diego-based diagnostic company Quidel, this test is easily performed with a nasal swab and offers results in just 10 minutes. Last week, the test was among several authorized by the Food and Drug Administration (FDA) for over-the-counter use to screen for COVID-19 at home.
Participants can order their QuickVue test kits online for home delivery or local pick up. A free online tool, which was developed with NIH support by CareEvolution, LLC, Ann Arbor, MI, will also be available to provide testing instructions, help in understanding test results, and text message reminders about testing. This innovative tool is also available as a smartphone app.
A recent study, supported by the RADx initiative, found that rapid antigen testing for COVID-19, when conducted at least three times per week, achieves a viral detection level on par with the gold standard of PCR-based COVID-19 testing processed in a lab [1]. That’s especially significant considering the other advantages of a low-cost, self-administered rapid test, including confidential results at home in minutes.
The Say Yes! COVID Test initiative is an important next step in informing the best testing strategies in communities all over the country to end this and future pandemics. The initiative will also help to determine how readily people accept such testing when it’s made available to them. If the foundational data looks promising, the hope is that rapid at-home tests will help to encourage people to protect themselves and others by following the three W’s (Wear a mask. Wash your hands. Watch your distance), getting vaccinated, and saying “Yes” to the COVID-19 test.
Reference:
[1] Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection. Smith RL, Gibson LL, Martinez PP, Heetderks WJ, McManus DD, Brooke CB, et al. medRxiv, 2021 March 20.
Links:
CDC and NIH bring COVID-19 self-testing to residents in two locales, NIH News Release, March 31, 2021
Rapid Acceleration of Diagnostics (RADx) (NIH)
COVID-19 Testing (CDC)
Quidel Corporation (San Diego, CA)
Coronavirus (COVID-19) Update: FDA Continues to Advance Over-the Counter and Other Screening Test Development, FDA News Release, March 31, 2021
NIH Support: National Heart, Lung, and Blood Institute; National Institute of Biomedical Imaging and Bioengineering
First Anniversary of NIH’s COVID-19 Testing Car Line
Posted on by Dr. Francis Collins
Citizen Scientists Take on the Challenge of Long-Haul COVID-19
Posted on by Dr. Francis Collins
Coronaviruses are a frequent cause of the common cold. Most of us bounce back from colds without any lasting health effects. So, you might think that individuals who survive other infectious diseases caused by coronaviruses—including COVID-19—would also return to normal relatively quickly. While that can be the case for some people, others who’ve survived even relatively mild COVID-19 are experiencing health challenges that may last for weeks or even months. In fact, the situation is so common, that some of these folks have banded together and given their condition a name: the COVID “long-haulers.”
Among the many longer-term health problems that have been associated with COVID-19 are shortness of breath, fatigue, cognitive issues, erratic heartbeat, gastrointestinal issues, low-grade fever, intolerance to physical or mental activity, and muscle and joint pains. COVID-19 survivors report that these symptoms flair up unpredictably, often in different combinations, and can be debilitating for days and weeks at a time. Because COVID-19 is such a new disease, little is known about what causes the persistence of symptoms, what is impeding full recovery, or how to help the long-haulers.
More information is now emerging from the first detailed patient survey of post-COVID syndrome, also known as Long COVID [1]. What’s unique about the survey is that it has been issued by a group of individuals who are struggling with the syndrome themselves. These citizen scientists, who belong to the online Body Politic COVID-19 Support Group, decided to take matters into their own hands. They already had a pretty good grip on what sort of questions to ask, as well as online access to hundreds of long-haulers to whom they could pose the questions.
The citizen scientists’ group, known as the Patient-led Research for COVID-19, brought a lot of talent and creativity to the table. Members reside in the United States, Canada, and England, and none have ever met face to face. But, between their day jobs, managing time differences, and health challenges, each team member spends about 20 hours per week working on their patient-led research, and are now putting the final touches on a follow-up survey that will get underway in the next few weeks.
For their first survey, the group members faced the difficult decision of whom to contact. First, they needed to define long hauler. For that, they decided to target people whose symptoms persisted for more than 2 weeks after their initial recovery from COVID-19. The 640 individuals who responded to the survey were predominately white females between the ages of 30 to 49 who lived in the United States. The members said that the gender bias may stem from women being more likely to join support groups and complete surveys, though there may be a gender component to Long COVID as well. About 10 percent of respondents reported that they had ultimately recovered from this post-COVID syndrome.
Another important issue revolved around COVID-19 testing. Most long-haulers in the online group had gotten sick in March and April, but weren’t so sick that they needed to be hospitalized. Because COVID-19 testing during those months was often limited to people hospitalized with severe respiratory problems, many long-haulers with mild or moderate COVID-like symptoms weren’t tested. Others were tested relatively late in the course of their illness, which can increase the likelihood of false negatives.
The team opted to cast a wide investigative net, concluding that limiting its data to only people who tested positive for COVID-19 might lead to the loss of essential information on long-haulers. It turns out that half of the respondents hadn’t been tested for SARS-CoV-2, the virus that causes COVID-19. The other half was divided almost equally between those who tested positive and those who tested negative. Here are some highlights of the survey’s findings:
Top 10 Symptoms: Respondents were asked to rank their most common symptoms and their relative severity. From highest to lowest, they were: mild shortness of breath, mild tightness of chest, moderate fatigue, mild fatigue, chills or sweats, mild body aches, dry cough, elevated temperature (98.8-100), mild headache, and brain fog/concentration challenges. Highlighting the value of patient-led research, the team was able to assemble an initial list of 62 symptoms that long-haulers often discuss in support groups. The survey revealed common symptoms that have been greatly underreported in the media, such as neurological symptoms. These include brain fog, concentration challenges, and dizziness.
Making a Recovery: Of the 60 respondents who had recovered, the average time to recovery was 27 days. The respondents who had not recovered had managed their symptoms for 40 days on average, with most dealing with health problems for 5 to 7 weeks. The report shows that the chance of full recovery by day 50 is less than 20 percent.
Exercise Capacity: About 65 percent of respondents now consider themselves mostly sedentary. Most had been highly physically active before developing COVID-19. Many long-haulers expressed concern that overexertion causes relapses
Testing. Respondents who reported testing positive for SARS-CoV-2 were tested on average earlier in their illness (by day 10) than those who reported testing negative (by day 16). The team noted that their findings parallel those in a recent published scientific study, which found false-negative rates for current PCR-based assays rose as the time between SARS-CoV-2 infection and testing increased [2]. In that published study, by day 21, the false-negative rate reached 66 percent. Only two symptoms (loss of smell and loss of taste) occurred more frequently in respondents who tested positive; the other 60 symptoms were statistically the same between groups. The citizen scientists speculate that testing is not capturing a subset of COVID patients, and more investigation is required.
Since issuing their survey results on May 11, the team has met with staff from the Centers for Disease Control and Prevention and the World Health Organization. Their work also been mentioned in magazine articles and even cited in some papers published in scientific journals.
In their next survey, these citizen scientists hope to fill in gaps in their first report, including examining antibody testing results, neurological symptoms, and the role of mental health. To increase geographic and demographic diversity, they will also translate the survey into 10 languages. If you’re a COVID-19 long-hauler and would like to find out how to get involved, there’s still time to take part in the next survey.
References:
[1] “What Does COVID-19 Recovery Actually Look Like?” Patient-led Research for COVID-19. May 11, 2020.
[2] Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure. Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Ann Intern Med. 2020 Aug 18;173(4):262-267.
Links:
Coronavirus (COVID-19) (NIH)
Charting a Rapid Course Toward Better COVID-19 Tests and Treatments
Posted on by Dr. Francis Collins
It is becoming apparent that our country is entering a new and troubling phase of the pandemic as SARS-CoV-2, the novel coronavirus that causes COVID-19, continues to spread across many states and reaches into both urban and rural communities. This growing community spread is hard to track because up to 40 percent of infected people seem to have no symptoms. They can pass the virus quickly and unsuspectingly to friends and family members who might be more vulnerable to becoming seriously ill. That’s why we should all be wearing masks when we go out of the house—none of us can be sure we’re not that asymptomatic carrier of the virus.
This new phase makes fast, accessible, affordable diagnostic testing a critical first step in helping people and communities. In recognition of this need, NIH’s Rapid Acceleration of Diagnostics (RADx) initiative, just initiated in late April, has issued an urgent call to the nation’s inventors and innovators to develop fast, easy-to-use tests for SARS-CoV-2, the novel coronavirus that causes COVID-19. It brought a tremendous response, and NIH selected about 100 of the best concepts for an intense one-week “shark-tank” technology evaluation process.
Moving ahead at an unprecedented pace, NIH last week announced the first RADx projects to come through the deep dive with flying colors and enter the scale-up process necessary to provide additional rapid testing capacity to the U.S. public. As part of the RADx initiative, seven biomedical technology companies will receive a total of $248.7 million in federal stimulus funding to accelerate their efforts to scale up new lab-based and point-of-care technologies.
Four of these projects will aim to bolster the nation’s lab-based COVID-19 diagnostics capacity by tens of thousands of tests per day as soon as September and by millions by the end of the year. The other three will expand point-of-care testing for COVID-19, making results more rapidly and readily available in doctor’s offices, urgent care clinics, long-term care facilities, schools, child care centers, or even at home.
This is only a start, and we expect that more RADx projects will advance in the coming months and begin scaling up for wide-scale use. In the meantime, here’s an overview of the first seven projects developed through the initiative, which NIH is carrying out in partnership with the Office of the Assistant Secretary of Health, the Biomedical Advanced Research and Development Authority, and the Department of Defense:
Point-of-Care Testing Approaches
Mesa Biotech. Hand-held testing device detects the genetic material of SARS-CoV-2. Results are read from a removable, single-use cartridge in 30 minutes.
Quidel. Test kit detects protein (viral antigen) from SARS-CoV-2. Electronic analyzers provide results within 15 minutes. The U.S. Department of Health and Human Service has identified this technology for possible use in nursing homes.
Talis Biomedical. Compact testing instrument uses a multiplexed cartridge to detect the genetic material of SARS-CoV-2 through isothermal amplification. Optical detection system delivers results in under 30 minutes.
Lab-based Testing Approaches
Ginkgo Bioworks. Automated system uses next-generation sequencing to scan patient samples for SARS-CoV-2’s genetic material. This system will be scaled up to make it possible to process tens of thousands of tests simultaneously and deliver results within one to two days. The company’s goal is to scale up to 50,000 tests per day in September and 100,000 per day by the end of 2020.
Helix OpCo. By combining bulk shipping of test kits and patient samples, automation, and next-generation sequencing of genetic material, the company’s goal is to process up to 50,000 samples per day by the end of September and 100,000 per day by the end of 2020.
Fluidigm. Microfluidics platform with the capacity to process thousands of polymerase chain reaction (PCR) tests for SARS-CoV-2 genetic material per day. The company’s goal is to scale up this platform and deploy advanced integrated fluidic chips to provide tens to hundreds of thousands of new tests per day in the fall of 2020. Most tests will use saliva.
Mammoth Biosciences. System uses innovative CRISPR gene-editing technology to detect key pieces of SARS-CoV-2 genetic material in patient samples. The company’s goal is to provide a multi-fold increase in testing capacity in commercial laboratories.
At the same time, on the treatment front, significant strides continue to be made by a remarkable public-private partnership called Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV). Since its formation in May, the partnership, which involves 20 biopharmaceutical companies, academic experts, and multiple federal agencies, has evaluated hundreds of therapeutic agents with potential application for COVID-19 and prioritized the most promising candidates.
Among the most exciting approaches are monoclonal antibodies (mAbs), which are biologic drugs derived from neutralizing antibodies isolated from people who’ve survived COVID-19. This week, the partnership launched two trials (one for COVID-19 inpatients, the other for COVID-19 outpatients) of a mAB called LY-CoV555, which was developed by Eli Lilly and Company, Indianapolis, IN. It was discovered by Lilly’s development partner AbCellera Biologics Inc. Vancouver, Canada, in collaboration with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). In addition to the support from ACTIV, both of the newly launched studies also receive support for Operation Warp Speed, the government’s multi-agency effort against COVID-19.
LY-CoV555 was derived from the immune cells of one of the very first survivors of COVID-19 in the United States. It targets the spike protein on the surface of SARS-CoV-2, blocking it from attaching to human cells.
The first trial, which will look at both the safety and efficacy of the mAb for treating COVID-19, will involve about 300 individuals with mild to moderate COVID-19 who are hospitalized at facilities that are part of existing clinical trial networks. These volunteers will receive either an intravenous infusion of LY-CoV555 or a placebo solution. Five days later, their condition will be evaluated. If the initial data indicate that LY-CoV555 is safe and effective, the trial will transition immediately—and seamlessly—to enrolling an additional 700 participants with COVID-19, including some who are severely ill.
The second trial, which will evaluate how LY-CoV555 affects the early course of COVID-19, will involve 220 individuals with mild to moderate COVID-19 who don’t need to be hospitalized. In this study, participants will randomly receive either an intravenous infusion of LY-CoV555 or a placebo solution, and will be carefully monitored over the next 28 days. If the data indicate that LY-CoV555 is safe and shortens the course of COVID-19, the trial will then enroll an additional 1,780 outpatient volunteers and transition to a study that will more broadly evaluate its effectiveness.
Both trials are later expected to expand to include other experimental therapies under the same master study protocol. Master protocols allow coordinated and efficient evaluation of multiple investigational agents at multiple sites as the agents become available. These protocols are designed with a flexible, rapidly responsive framework to identify interventions that work, while reducing administrative burden and cost.
In addition, Lilly this week started a separate large-scale safety and efficacy trial to see if LY-CoV555 can be used to prevent COVID-19 in high-risk residents and staff at long-term care facilities. The study isn’t part of ACTIV.
NIH-funded researchers have been extremely busy over the past seven months, pursuing every avenue we can to detect, treat, and, ultimately, end this devasting pandemic. Far more work remains to be done, but as RADx and ACTIV exemplify, we’re making rapid progress through collaboration and a strong, sustained investment in scientific innovation.
Links:
Coronavirus (COVID-19) (NIH)
Rapid Acceleration of Diagnostics (RADx)
Video: NIH RADx Delivering New COVID-19 Testing Technologies to Meet U.S. Demand (YouTube)
Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)
Explaining Operation Warp Speed (U.S. Department of Health and Human Resources/Washington, D.C.)
“NIH delivering new COVID-19 testing technologies to meet U.S. demand,” NIH news release,” July 31, 2020.
“NIH launches clinical trial to test antibody treatment in hospitalized COVID-19 patients,” NIH new release, August 4, 2020.
“NIH clinical trial to test antibodies and other experimental therapeutics for mild and moderate COVID-19,” NIH news release, August 4, 2020.
Racing to Develop Fast, Affordable, Accessible Tests for COVID-19
Posted on by Dr. Francis Collins
Developing faster, more convenient ways of testing for coronavirus disease 2019 (COVID-19) will be essential to our efforts to end this deadly pandemic. Despite the tremendous strides that have been made in diagnostics over the past seven months, we still need more innovation.
We need reliable, affordable tests for the presence SARS-CoV-2—the novel coronavirus that causes COVID-19—that do not take hours or days to deliver results. We need tests that are more user friendly, and that don’t rely on samples collected by swabs that have to be inserted deep into the nose by someone wearing PPE. We need tests that can be performed at the point-of-care, whether a doctor’s office, urgent care clinic, long-term care facility, or even a home. Ideally, such tests should also be able to integrate with mobile devices to convey results and transmit data seamlessly. Above all, we need tests that are accessible to everyone.
Most current diagnostic tests for SARS-CoV-2 involve detecting viral genetic material using a decades-old technology called the polymerase chain reaction (PCR). If there’s even a tiny bit of viral genetic material in a patient’s sample, PCR can amplify the material millions of times so that it can be readily detected. The problem is that this amplification process is time-consuming and requires a thermal cycling machine that’s generally operated by trained personnel in sophisticated lab settings.
To spur the creation of new approaches that can rapidly expand access to testing, NIH launched the Rapid Acceleration of Diagnostics (RADx) program in late April 2020. This fast-paced, innovative effort, conducted in partnership with the Office of the Assistant Secretary of Health, the Biomedical Advanced Research and Development Authority (BARDA), and the Department of Defense, is supported by $1.5 billion in federal stimulus funding. The goal? To expand diagnostic testing capacity for COVID-19 in the United States to about 6 million tests per day by December. That’s quite a leap forward because our nation’s current testing capacity is currently about 1 million tests per day.
Just yesterday, I joined other NIH leaders in authoring a special report in the New England Journal of Medicine that describes RADx’s main activities, and provides an update on the remarkable progress that’s been made in just three short months [1]. In a nutshell, RADx consists of four components: RADx-tech, RADx Advanced Technology Platforms (RADx-ATP). RADx Radical (RADx-rad), and RADx Underserved Populations (RADx-UP).
Though all parts of RADx are operating on a fast-track, RADx-tech has embraced its rapid timelines in a can-do manner unlike anything that I’ve encountered in my 27 years in government. Here’s how the process, which has been likened to a scientific “shark tank,” works.
Once an applicant submits a test idea to RADx-tech, it’s reviewed within a day by a panel of 30 experts. If approved, the application moves to a highly competitive “shark-tank” in which a team of experts spend about 150 to 200 person-hours with the applicant evaluating the technical, clinical, and commercial strengths and weaknesses of the proposed test.
From there, a detailed proposal is presented to a steering committee, and then sent to NIH. If we at NIH think it’s a great idea, promising early-stage technologies enter what’s called “phase one” development, with considerable financial support and the expectation that the applicant will hit its validation milestones within a month. Technologies that succeed can then go to “phase two”, where support is provided for scale-up of tests for meeting regulatory requirements and supporting manufacture, scale-up, and distribution.
The major focus of RADx-tech is to simplify and speed diagnostic testing for COVID-19. Tests now under development include a variety of mobile devices that can be used at a doctor’s office or other point-of-care settings, and give results in less than an hour. In addition, about half of the tests now under development use saliva or another alternative to samples gathered via nasal swabs.
As Americans think about how to move back safely into schools, workspaces, and other public areas in the era of COVID-19, it is clear that we need to figure out ways to make it easier for everyone to get tested. To attain that goal, RADx has three other components that build on different aspects of this social imperative:
• RADx Advanced Technology Platforms (RADx-ATP). This program offers a rapid-response application process for firms with existing point-of-care technologies authorized by the Food and Drug Administration (FDA) for detecting SARS-CoV-2. These technologies are already advanced enough that they don’t need the shark tank. The RADx-ATP program provides support for scaling up production to between 20,000 and 100,000 tests per day by the fall. Another component of this program provides support for expanding automated “mega-labs” to increase testing capacity across the country by another 100,000 to 250,000 tests per day.
• RADx Radical (RADx-rad). The program seeks to fuel the development of truly futuristic testing technologies. For example, it supports projects that use biomarkers to detect an infection or predict the severity of disease, including the likelihood of developing COVID-related multisystem inflammatory syndrome in children (MIS-C). Other areas of interest include the use of biosensors to detect the presence of the virus in a person’s breath and the analysis of wastewater to conduct community-based surveillance.
• RADx Underserved Populations (RADx-UP). Data collected over the past several months make it clear that Blacks, Latinxs, and American Indians/Alaska Natives are hospitalized and die of COVID-19 at disproportionately higher rates than other groups. RADx-UP aims to engage underserved communities to improve access to testing. Such actions will include closely examining the factors that have led to the disproportionate burden of the pandemic on underserved populations, as well as building infrastructure that can be leveraged to provide optimal access and uptake of SARS-CoV-2 testing in such communities.
At NIH, we have great hopes for what RADx-supported research will do to help bring to an end the greatest public health crisis of our generation. Yet the benefits may not end there. The diagnostic testing technologies developed here will have many other applications moving forward. Long after the COVID-19 pandemic becomes a chapter in history books, I’m convinced the RADx model of rapid innovation will be inspiring future generations of researchers as they look for creative new ways to address other diseases and conditions.
Reference:
[1] Rapid scaling up of COVID-19 diagnostic testing in the United States—The NIH RADx Initiative. Tromberg BJ, Schwetz TA, Perez-Stable E, Hodes RJ. Woychick RP, Bright RA, Fleurence RL, Collins FS. NEJM; 2020 July 16. [Online publication ahead of print]
Links:
Coronavirus (COVID-19) (NIH)
Rapid Acceleration of Diagnostics (RADx)
“NIH mobilizes national innovation initiative for COVID-19 diagnostics,” NIH news release, April 29, 2020.
Swimming with the High-Tech Sharks to Improve COVID-19 Testing
Posted on by Dr. Francis Collins
So much has been reported over the past six months about testing for coronavirus disease 2019 (COVID-19) that keeping up with the issue can be a real challenge. To discuss the latest progress on new technologies for SARS-CoV-2 diagnostic testing in the United States, I spoke recently with NIH’s Dr. Bruce Tromberg, director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). Not only does Bruce run a busy NIH institute, he is helping to coordinate the national response for expanded testing during the COVID-19 pandemic.
Bruce also has a leading role in one of NIH’s most-exciting new initiatives. It’s called the Rapid Acceleration of Diagnostics (RADx) initiative, and it is on the fast track to bolster the country’s diagnostic testing capacity within months. Here’s a condensed transcript of our chat, which took place via videoconference, with Bruce linking in from Bethesda, MD and me from my home in Chevy Chase, MD:
Collins: Let’s start with how many COVID-19 tests are being done right now per day in the United States. By that, I’m referring to testing for the presence of the novel coronavirus, not antibodies as a sign of a previous infection.
Tromberg: The numbers fluctuate—anywhere from around 400,000 to 900,000 tests per day. So, the national capacity, with all these complex laboratory tests and emerging point-of-care assays, is getting close to 1 million a day. That’s substantially higher than in mid-April, when the nation was doing about 150,000 tests per day. But most testing is still being done in laboratories or complex facilities, and it can take a while for those tests to be run and for people to get answers. What we’d like to have are more convenient tests. We’d like to have tests that people can have at the point of care, where you get an answer on the spot and very quickly, or tests that can be performed easily in their homes.
Collins: Yes, we’d all love to have point-of-care tests for COVID-19. And there are some out there already. Every time I go to the White House, they have this gadget, called Abbott ID Now, that gives a result in about 15 minutes. That sounds pretty good. Do we just need to make more of those machines to solve the problem?
Tromberg: Abbott ID Now is one of the first point-of-care technologies. It’s not complicated, so a specialized laboratory isn’t required to run them. That’s what makes Abbott ID Now very appealing, but its performance could be better. There’s a bit of a risk when it’s used in individuals for which you really need to know, with absolute certainty, if they have the virus or not. Those performance issues have created opportunities to build platforms that are better, faster, and possible for people to do on their own.
Collins: Congress provided a big infusion of resources last April to assist in the development of new diagnostic technologies for COVID-19. A lot of that infusion came to NIH, and, Bruce, you were asked to step in and make something amazing happen on a timetable that’s pretty breathtaking. It’s called the RADx Initiative. Tell us a little about that.
Tromberg: RADx is short for Rapid Acceleration of Diagnostics. The goal of the initiative is to make it possible for everyone to have access to diagnostic testing for COVID-19 as easily and quickly as possible. As we pivot to doing surveillance in large populations, we will need greater testing capacity to help optimize the management of each individual. So, that’s really the aim of RADx, or RADx-tech, which is a special flavor of RADx.
Collins: Right, the goal of RADx-tech, which you are overseeing, is to identify some of these exciting new technologies and help scale them up quickly to the point where they can help people across the nation. Could you give us some examples?
Tromberg: Sure. One general class of technologies is called a lateral flow assay. These tests are small enough to fit in your hand and come in a convenient container. Basically, you can use a swab from your oral cavity and place it on one of the pads, and then you add a little bit of solution. The actual assay itself has a membrane inside of a little plastic container. The fluid flows across the membrane, and there’s chemistry that goes on inside the container to detect, for example, genetic material from the coronavirus. So, it can tell you if there is a presence of virus inside the swab. It’s very quick and straightforward. A line will “light up” if virus is present.
Another type of lateral flow assay, also small enough to hold in your hand, looks for proteins on the surface of the virus. You don’t have to break up the virus particle itself, but in this specific example, what captures the virus in this membrane is what’s called an aptamer. An aptamer is similar to an antibody, except it’s made from nucleic acid. It’s designed to bind very tightly with any molecule of interest. If you put a saliva sample into this assay, it moves up the membrane and some chemistry takes place. And then, you’ll see a line appear if there’s presence of a virus.
Collins: You just said saliva. I think a lot of people would much prefer, if they had to provide a sample, to use saliva instead of having a swab stuck in their nose, especially if it has to go all the way to the back of the nose. Does saliva work?
Tromberg: We hope so. Right now, RADx-tech has at least nine companies that are in what we call phase one, which is a significant step towards commercialization. Of those companies, more than half are looking at saliva or other kinds of sampling that’s not sticking swabs way up into the nasal cavity.
Another type of test is a lateral flow assay that fits directly into a mobile device like a tablet. It has a separate lateral flow apparatus, which looks like an elongated zip drive, and it slides right into the tablet itself. It’s something that’s not complicated. It would be easy to do at home. But rather than watching for the presence of a reaction, you look for a light inside the tablet to say the result is ready. And then, there is another color of light that comes directly from the lateral flow strip, that’s an indicator that the virus is present.
One last example is a nucleic acid test. This rectangular, hand-held device (see photo), reminiscent of a computer disc, looks inside the virus to amplify small traces of its nucleic acid to detectable levels. It is completely self-contained. To find that technology today, you generally must go to complex laboratories where the test is done on big machines, operated in multiple steps. Efforts are being made to reduce the size and the complexity of these devices so they can move out to point of care, without sacrificing the performance that we expect from a laboratory-based device.
Collins: That’s totally cool. Is the nucleic-acid test device that you just mentioned made for one-time use, and then you throw it away?
Tromberg: That’s their business model right now. I should probably mention something about cost. For example, you can imagine scaling up lateral flow assays very quickly to make tens of millions of tests. The components are inexpensive, and the tests may cost just a few dollars to make.
If you’re throwing away a nucleic acid test with its more-expensive components, obviously, the cost will be higher. Right now, if you go to a laboratory for a nucleic acid test, the cost may be on the order of $40 or so. With these one-time-use nucleic acid tests, the aim is to scale up the manufacturing to produce larger volumes that will bring the cost down. The estimates are maybe $60 per test.
Collins: That needs to come down more, obviously. In the months ahead, we’re talking about testing millions of people, maybe even fairly often to make sure that they haven’t been infected by SARS-CoV-2, the novel coronavirus that causes COVID-19. Is frequent testing the kind of thing that you’d like to be able to do by next fall?
Tromberg: Yes, and I think that that really speaks to the diversity of the types of tests that we need. I think there is a market, or the capacity, for some of the more expensive tests, if they’re extremely accurate and convenient. So, the nucleic acid test may cost more, but it will give you an answer very quickly and with very high sensitivity. It’s also very convenient. But the performance of that test may be very different from a standard lateral flow assay. Those tests will be far more accessible and very, very inexpensive, but they may have a higher false negative rate. We envision that every test that comes out of our innovation funnel will have documentation about its best-use case.
Collins: You mentioned your innovation funnel, sometimes called a “shark tank.” Say a little more about the RADx-tech shark tank. Who gets into it, and what happens when they get there?
Tromberg: At NIH, we’re into processes, and NIBIB created a very effective one 13 years ago with the Point of Care Technology Research Network (POCTRN). We’ve now leveraged this network to focus almost exclusively on COVID testing. POCTRN has five sites in the US. All have core resources, personnel, and expertise that are contributing to RADx-tech. Those include the ability to validate tests independently, the ability to do clinical studies in real-world samples and patients, and the ability to analyze manufacturing and scale-up needs while creating a roadmap for every project team to follow.
We have more than 200 people around the country working day and night on this process. If anyone has an idea about a COVID-19 test, you can and apply for funding on the POCTRN website. Your application will be reviewed by a panel of 30 experts within a day and, if approved, will move to the next stage, which is the shark tank.
In the shark tank [also called phase zero], a team of experts will spend about 150 to 200 person-hours with you evaluating the strengths and weaknesses of your test technically, clinically, and commercially. From this careful analysis, a detailed proposal will be presented to a steering committee, then sent to NIH. If we think it’s a great idea, the project will enter what we call phase one, with considerable financial support and the expectation that the company will hit its validation milestones within a month.
Collins: How far have things progressed, given that you just started RADx on April 29?
Tromberg: We have almost 60 projects that have entered or emerged from this shark-tank stage. I’m expecting that we’ll have around 15 projects in the phase one stage this month, and it’s very exciting to see them move there. If they can reach their validation milestones in that first month, they will be eligible to move to phase two. It involves a much larger chunk of money, so companies can move into manufacturing and scale up for distribution. We’re hoping to have between five and 10 companies emerge over time from this innovation funnel. But, by the end of the summer, we’d like to see at least two come out with products that will make a difference.
Collins: Wow, that’s just a few months away. How will you can get there so fast?
Tromberg: Sure. Some companies are further along than others. I can think of one that is quite far along with an established platform concept. This company has lots of expertise and has raised lots of money. We may be able to give them the surge that they need, plus the additional support with regulatory issues, commercialization, and manufacturing, in that short period of time to go to market.
Complementing that work is another of our initiatives called Advanced Technology Platforms (RADx-ATP). It’s designed to scale up existing technologies. For example, I mentioned a one-time-use nucleic acid test. It still needs validation, emergency use authorization, a little bit of manufacturing optimization. But we have other platforms out there that are much closer to commercialization, and RADx-ATP could be very impactful in getting some of those technologies out earlier.
Collins: You mentioned RADx-ATP, and we’ve been talking about RADx-tech, which is your shark tank approach. But there are a couple of other RADx components. Say something about those, please.
Tromberg: Our centerpiece component for doing demonstration projects is called RADx-UP. This is an effort across NIH to provide cutting-edge testing technologies in underserved populations. If I’m allowed to be the interviewer and turn the tables, I might bounce the question back to you. This is where your thinking directly influenced the whole RADx portfolio. So, maybe you can tell us more.
Collins: I can try. It’s very clear that COVID-19 has hit certain populations particularly hard, especially African American and Hispanic communities. And yet, those communities often have the least access to testing, which is sort of upside-down. We want to help identify people who are infected quickly, do the quarantining, and prevent the infection from spreading. That has simply not worked very well in a lot of underserved communities.
With resources from Congress, we made it a very high priority to set up demonstration projects of these advanced technologies in communities that would benefit significantly from them. We’re trying to bring together two really important NIH priorities: technology development and addressing health disparities. I’ve got to say, at this particular moment, when we’re all really focused on the fact that our nation is still riddled with health disparities, health inequities, and even racism, this is a moment where we should be doing everything we can to try to take our scientific capabilities and apply them to finding solutions.
So, we’re all pretty excited about RADx-UP. But there’s one other RADx, and I’ll throw this one back to you. It’s called RADx-rad. What the heck is that, Bruce?
Tromberg: Well, RADx-rad is the home for the technologies that are really far forward and futuristic. These are the technologies that won’t quite be ready for the time pressure of the innovation funnel. But they’re fantastic ideas. They’re projects that may be non-traditional in terms of the application of technology. They have been generated largely by other NIH institutes and centers. They’re important ideas and projects that just need to be supported with a longer time-window of return. We don’t want to lose out on the energy and the ideas and the creativity of those concepts.
Collins: Right now, the focus is on COVID-19 and the need for testing, especially within this calendar year. We hope, by the end of 2020 or the early part of 2021, to have vaccines for COVID-19 ready to go. But, moving forward, there will be other events that will probably make us wish that we had point-of-care diagnostics. So, in the process of doing what you’re doing with all of these components, hopefully we’re also preparing for future challenges.
Bruce, you’re an optimistic guy. At the same time, we’ve got to be realistic. Around September, when schools and colleges are contemplating whether it’s safe to open up, what would we hope that RADx could contribute to make that a better outcome?
Tromberg: That’s a tough question to answer, but I have a lot of confidence in our process. I’m confident that we’re engaging the innovation and entrepreneurial community in such a way that a lot of these ideas will move out and give us better performing tests and more of them. A rough number that I like to think about is the capacity to test roughly 2 percent of the population, around 6 million people per day. I think we’ll hit that target by the end of the year.
I’d like to see testing technologies move away from being based predominantly in laboratories. I’d like to see them more accessible to people as technologies that they can use in their homes. We’re now doing so many things from home. We’re working from home, we’re talking from home, we get our entertainment from home. Home-based testing is really the direction a lot of healthcare is going. We need to have these technologies. I think the level of sophistication and performance that we’re hoping for is possible, and the innovation and entrepreneurial community is working extremely hard to make it happen. No one has really asked us to do anything of this scale before, and I like to compare it to our Super Bowl.
Collins: Well, this is one exciting Super Bowl, that’s for sure! You’ve applied the venture capitalist strategy to RADx of trying to discover what’s out there, while not being afraid to invest in risky endeavors. You’re figuring out how to help promising technologies take their best shot and fail early, if they’re going to fail. And for technologies that are further along, you give them the needed resources to advance to commercialization.
We have great hopes and expectations that RADx will make a real difference. What we’re doing here is not just about cool science, it’s also about saving lives. I want to thank you for your incredible dedication, and your intellectual and engineering contributions to this initiative, which make it one of the most exciting things that NIH is doing right now.
Tromberg: Thank you, Francis.
Links:
Coronavirus (COVID-19) (NIH)
Rapid Acceleration of Diagnostics (RADx)
“Social engineering and bioengineering together can thwart the COVID-19 pandemic,” Director’s Corner, National Institute of Biomedical Imaging and Bioengineering/NIH)
Video: RADx Tech and POCTRN: Diagnosing Disease-Delivering Health (NIBIB/NIH)
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