Shares ofNovavax(NASDAQ:NVAX)were sinking 12.8% lower as of 12:05 p.m. EDT on Monday. The decline came after Reuters reported that Novavax plans to begin delivering COVID-19 vaccine NVX-CoV2373 to the European Union near the end of 2021 but most of its commitment of up to 200 million doses won't be shipped until next year.
There's good news and bad news with Reuters' report. The good news is that Novavax appears to be close to finalizing a major supply deal with the EU. The company reached a preliminary agreement with the 27-member economic and political union in December. However, the deal wasn't finalized at that time because Novavax has experienced difficulties sourcing some raw materials.
What's the bad news? Many investors were hoping that Novavax would see European sales for its COVID-19 vaccine sooner than late 2021 and 2022. With the biotech stock falling today, it's clear that the bad news is outweighing the good news in investors' minds.
At this point, neither Novavax nor the EU has officially commented on the supply agreement. However, European Commission President Ursula von der Leyen hinted in late April that a final deal with Novavax could be on the way. In the announcement of an imminent larger supply agreement with Pfizer and BioNTech, she stated, "We will certainly add other potential vaccines, for example protein-based vaccines have also quite a potential." Novavax's NVX-CoV2373 is a protein-based vaccine.
The most important thing Novavax needs to do now is to win Emergency Use Authorization (EUA) for NVX-CoV2373. The company has already initiated regulatory filings in the EU, U.K., Canada, Australia, and New Zealand.
Avrobio Inc (NASDAQ: AVRO) has provided an update on its regulatory plans for AVR-RD-01, its lentiviral gene therapy for Fabry disease, currently in FAB-GT Phase 2 trial.
In March, the FDA granted full approval to Sanofi's SA (NASDAQ: SNY) Fabrazyme (agalsidase beta) after it received accelerated approval based on a surrogate endpoint of reduction of GL-3 inclusions in biopsied renal peritubular capillaries (PTCs).
The conversion of Fabrazyme to full approval limits the accelerated approval pathways available for new therapies to treat Fabry disease.
Hence, Avrobio can no longer pursue an accelerated approval pathway for AVR-RD-01 and instead plans to discuss with FDA a registration trial with a primary efficacy endpoint of clearance of GL-3/Gb3 inclusions in biopsied renal PTCs.
Registration trial is expected to initiate in mid-2022.
To support the use of AVR-RD-01 in a broad Fabry disease population, the company expects to include female patients, eliminate antibody status exclusions and collect additional cardiovascular and CNS data in its ongoing FAB-GT trial.
SARS-CoV-2 started spreading towards the end of 2019 causing COVID-19, a disease that reached pandemic proportions among the human population within months. The reasons for the spectrum of differences in the severity of the disease across the population, and in particular why the disease affects more severely the aging population and those with specific preconditions are unclear. We developed machine learning models to mine 240,000 scientific papers openly accessible in the CORD-19 database, and constructed knowledge graphs to synthesize the extracted information and navigate the collective knowledge in an attempt to search for a potential common underlying reason for disease severity. The literature repeatedly pointed to elevated blood glucose as a key facilitator in the progression of COVID-19. Indeed, when we retraced the steps of the SARS-CoV-2 infection we found evidence linking elevated glucose to each step of the life-cycle of the virus, progression of the disease, and presentation of symptoms. Specifically, elevations of glucose provide ideal conditions for the virus to evade and weaken the first level of the immune defense system in the lungs, gain access to deep alveolar cells, bind to the ACE2 receptor and enter the pulmonary cells, accelerate replication of the virus within cells increasing cell death and inducing an pulmonary inflammatory response, which overwhelms an already weakened innate immune system to trigger an avalanche of systemic infections, inflammation and cell damage, a cytokine storm and thrombotic events. We tested the feasibility of the hypothesis by analyzing data across papers, reconstructing atomistically the virus at the surface of the pulmonary airways, and performing quantitative computational modeling of the effects of glucose levels on the infection process. We conclude that elevation in glucose levels can facilitate the progression of the disease through multiple mechanisms and can explain much of the variance in disease severity seen across the population. The study proposes diagnostic recommendations, new areas of research and potential treatments, and cautions on treatment strategies and critical care conditions that induce elevations in blood glucose levels.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This study was supported by funding to the Blue Brain Project, a research center of the Ecole polytechnique federale de Lausanne (EPFL), from the Swiss government ETH Board of the Swiss Federal Institutes of Technology.
Six patients with dementia traveled to Mexico last year to be injected with a gene therapy not authorized for use in the U.S., according to the CEO of a Seattle-area startup that wants to accelerate testing of unproven anti-aging medicines and views U.S. drug safety regulations as a hindrance.
At the heart of the project is a controversial biotech called BioViva, whose CEO had herself injected with an experimental gene therapy in Colombia and whose advisory board includes renowned Harvard geneticist George Church. It is part of a growing ecosystem of entrepreneurs and scientists, dreamers and schemers, who believe aging is not inevitable and aim to develop treatments to extend the human life span.
Last month, during a talk hosted by the National University of Singapore, the CEO, Elizabeth Parrish, divulged that she was eagerly awaiting data from a human study involving six patients who received an experimental gene therapy. On Friday, she told STAT the procedures were done last year in Mexico. If true, it would be the first known attempt to use the technique to treat age-related dementia, which is most often caused by Alzheimer’s disease.
STAT set out to independently verify the accuracy of Parrish’s claims. While many key details could not be confirmed, including the identities of these six patients and how the purported treatment affected them, STAT found evidence that BioViva and partners were recruiting patients. A newsletter emailed by BioViva in 2019 said 10 patients over age 50 with mild to moderate Alzheimer’s were needed for a study of a gene therapy. The one-hour procedure, according to an FAQ linked from the email, would be done in Mexico City and involved a one-time injection.
The effort raises the specter of an overseas medical tourism industry targeting patients desperate to lengthen their lives and offering unproven treatments that would permanently alter the genetic code inside recipients’ cells.
The idea for gene therapy — using an innocuous virus to slip a good copy of a gene into the DNA of people’s cells to correct a disease-causing mutation — was first published in 1972. After decades of fits and starts, including some deaths in experimental trials, the U.S. Food and Drug Administration finally approved one of these medicines in 2017. Since then, at least nine more gene therapies have made it to market, for treating certain kinds of cancer and a few rare genetic disorders.
Parrish considers aging to be a disease, one that might be treated in similar fashion — by supplementing people’s cells with bits of genetic code to lengthen their chromosomes, or supercharge muscle formation, or boost proteins that protect against oxidative stress. The basics of gene transfer technology have advanced sufficiently in recent years to be within reach of a small company like BioViva that wants to apply them to aging. But Parrish doesn’t want to wait the decades it might take to find out if these approaches actually work under the existing regulatory framework, which requires extensive laboratory and animal experiments before initiating costly human studies.
“The power of the technology is there, we’re just not able to harness it because nobody is able to raise the money to get these disruptive regenerative medicines into clinical trials,” Parrish told STAT in an interview. If it were up to her, the FDA would have a regulatory route that would allow doctors to take treatments that look promising in animal models and give them to willing patients. But since that doesn’t exist, sending patients overseas, and paying for their treatment is the next best thing in her view, because at least that jump-starts the process.
“With the first human data, that should be a banner to investors to come in and invest in the technology so the rest of the world can experience it,” she said.
Parrish founded BioViva in early 2015. Months later, according to an account she gave to a reporter for Outside, Parrish traveled to Bogotá, Colombia, where unbeknownst to her family, she received more than 100 injections of an experimental gene therapy intended to turn on an enzyme called telomerase. Telomerase is a protein that extends telomeres, a stabilizing cap found at the ends of chromosomes, and sometimes referred to as the “aging clock” because they get gradually worn down the older you get. When they get short enough, cells stop dividing. Boosting telomerase is a favorite approach among the anti-aging evangelists because cells that are functionally immortal — ones that can go on dividing forever, like stem cells and tumor cells — tend to express the protein at high levels.
This molecule, and its role in aging, had been discovered in the late 1970s by scientists Elizabeth Blackburn, Carol Greider, and Jack Szostak. Their work in algae and yeast cells later earned them a Nobel Prize. In the 1990s, scientists at the Bay Area biotech company Geron Corporation mapped the human gene for telomerase. Leading that team was a molecular biologist named Bill Andrews. Years later, he would design a virus packed with instructions to switch on telomerase for Parrish.
“I didn’t know at the time she was going to treat herself,” Andrews told STAT. But after she did, the two began making plans to open overseas gene therapy clinics under BioViva. By 2017 though, those plans had fizzled and Andrews licensed his technology to a different company, Libella Gene Therapeutics. Libella initially tried to recruit patients for a pay-to-participate test of its telomerase gene therapy, which it claimed was to be done in India, for treating mid- or late-stage Alzheimer’s disease. The expected cost for the first patient would be $11 million, Libella CEO Jeff Mathis told STAT in an interview in 2019.
That trial appears to have never taken place. Libella then attempted to recruit patients for a small trial in Colombia, this time charging patients $1 million for its telomere-repairing gene therapy. Company executives told MIT Technology Review it had recruited two patients, but in the interview with STAT, Andrews said no one has yet received the treatment. Mathis did not respond to phone calls or emails from STAT.
During that time, BioViva pivoted to bioinformatics. “That means we look at data from companies sponsoring studies and analyze it for them,” said Parrish. The main company BioViva works with is Integrated Health Systems, which markets itself as a broker connecting patients to a network of doctors operating outside the U.S. who are willing to provide unapproved treatments. On social media, IHS describes itself as “the gene therapy specialists.” On its website, IHS lists only one doctor, a radiologist named Jason R. Williams, who is also BioViva’s chief medical officer. He also runs a cancer immunotherapy practice in Mexico City called the Williams Cancer Institute.
In July 2019, BioViva posted a YouTube video, announcing that Integrated Health Systems was launching a study of telomerase gene therapy, and was looking for volunteers with symptoms of mild to moderate Alzheimer’s disease to participate. The video was also shared on Integrated Health Systems’ Facebook page. The following month, BioViva sent a newsletter to its subscribers, advertising the study, and saying that the $62,000 treatment would be offered free to participants, with the cost covered by Maximum Life Foundation, a nonprofit that funds aging research.
An FAQ document and sign-up form detailed that the study would be conducted at the Williams Cancer Institute in Mexico City. Participants would have to pay for their own travel. Once there, they would receive a single injection of the telomerase gene construct to “rejuvenate brain cells called microglial cells.” It was described as a one-hour procedure, but patients were advised to stay in the area for four to five days in the event of an adverse reaction. These documents indicate that IHS screened candidates in the spring of 2019, and planned to schedule the treatments between April and October of that year.
IHS described candidates as otherwise healthy individuals over the age of 50 with a probable Alzheimer’s diagnosis and a reliable caregiver to accompany them to the study site. “Please note that it is critical that you commit to the entire process so that this study can provide credible results to move into larger populations,” the FAQ states. “It is an honor to have you apply and participate.”
The language of these materials, touting potential cures and working therapies, were both misleading and manipulative, said Leigh Turner, a bioethicist at the University of Minnesota who studies medical tourism and reviewed the documents for STAT. Under regulated clinical research, investigators would be required to disclose an approved study design and methodology to the public in a database like clinicaltrials.gov before recruiting participants. Such a listing should describe what patients will be receiving, and how much, and how often, and how it will be administered, where it will be administered, what metrics will be used to determine if the treatment worked, and what the rules are for stopping if something starts to go awry. Nearly all of that was missing here, he said.
“Everything I’m seeing indicates the involved parties are not conducting a credible clinical trial with appropriate safeguards,” said Turner.
IHS did not respond to STAT’s emailed questions. No phone number is listed on the IHS website, and no contact information is registered to the domain. In response to requests for more details about the company, Parrish referred STAT to IHS’s generic information email address. Dave Kekich, the president and CEO of Maximum Life Foundation, who is also director of strategic planning at BioViva, confirmed to STAT that IHS had treated six individuals, and said they had to show they had symptoms of dementia.
“This is an offshore medical tourism operation to test an experimental therapy,” he said. He referred questions about study specifics to Williams.
Emailed questions sent to Williams and his assistant in Alabama did not receive a response. A STAT reporter went to the Mexico City hospital listed as Williams’ affiliated inpatient facility, and verified through another radiologist there that Williams performs immunotherapy treatments at the hospital, but not gene therapy treatments, to this doctor’s knowledge. STAT identified three U.S. cancer patients who said they traveled to Mexico for immunotherapy treatments from Williams, after raising money via GoFundMe campaigns to pay for the procedures, which they described as costing between $100,000 and $120,000.
Williams has a history of providing unapproved treatments to desperate patients. In 2012, he opened a practice called Precision StemCell, which offered unproven stem cell treatments for everything from spinal cord injuries to ALS to inherited childhood blindness. Later that year, Turner wrote a letter to the FDA, asking the agency to intervene. Williams told MIT Tech Review in 2015 that he’d ceased providing those treatments in the U.S. in 2013, after the FDA asked him to stop because they required agency approval. He later established a clinic in Bogotá, Colombia, and launched a company called Neuralgene that claimed it was testing gene therapies for ALS delivered to the spinal cord. According to its website, Neuralgene has since relocated to Mexico along with Williams, who is listed as its CEO and director of R&D. No other employees are listed.
Parrish and Williams have known each other for years though rarely spend time together. She confirmed to STAT that he was the one who injected her with DNA-modifying viruses back in 2015. And the two appear in videos together on BioViva’s YouTube channel, talking about genetic approaches to staving off different aspects of aging — him beaming in a dark wood-paneled office, her floating in front of an ethereal black and gold background. During these conversations, Parrish often name-drops research the company is doing with Rutgers University. In other videos, she also mentions Harvard’s Church.
In 2018, BioViva began funding work in the Rutgers lab of microbiologist Hua Zhu, who studies herpes viruses. For the last few years, his team has been doing experiments in mice with one of these viruses in particular — a recombinant cytomegalovirus — to test it as an alternative gene therapy delivery system, or vector, to the more commonly used adeno-associated viruses (AAVs). In work that has not yet been published, Zhu’s team loaded up the cytomegalovirus with anti-aging gene targets, including telomerase. Compared to mice that didn’t get the treatment, these mice lived about 40% longer, he told STAT. “That’s very significant,” he said.
In 2015, Church’s lab accepted and analyzed some of Parrish’s blood samples from the Bogotá experiment. When asked whether his lab has received any samples or patient data from the six patients in the IHS dementia study, he said, “No, we have not.”
Turner, the bioethicist, is concerned that celebrity scientists like Church are lending credibility to an operation that might be putting people in harm’s way. “You don’t want to have academics at reputable institutions offering a protective function for what appears in many ways to be pretty disturbing activities on the part of these companies,” said Turner. ”So if he’s going to lend his name to businesses like this one, in a way, he becomes responsible for propping them up.”
Asked about Turner’s comment, Church wrote in an email: “Is helping a bit with a (quite different) mouse experiment at Rutgers … somehow ‘offering a protective function’?” He added that he has “stressed support for proper clinical trials in the past, and I still do.”
On Monday, after this story was posted, Church emailed to say he had reached out to Parrish: “I do feel that the critique seems fair and hence have contacted Liz to try to get additional clarification and potentially change some aspects,” he wrote.
One thing that’s still unclear is where IHS is obtaining the virally packaged genetic material needed for the treatment. Zhu said that his lab does work only in mice, and that he was not involved in creating vectors for any human studies. Virovek, a California biotech company that produces much of the AAV vectors used by American academic research institutions, did not answer questions about whether any treatment had been produced for IHS or Williams.
Parrish also denied that BioViva provided them. “We don’t have the capacity to manufacture vectors,” she said. Her team’s role in all this, she said, is to analyze the patient data from the six trial participants. She said she expects to have results from their eight-month follow-up to share with the public in early June.
“I am dying to see the data,” said Andrews. Even though he’s a BioViva competitor now, he wants to finally, after all these years, see a proof of concept. “I really hope they did it,” he said.
But not everyone involved is so enthusiastic.
“Telomerase has been shown to be rejuvenating in animals,” said Church. But is the science mature enough to move into humans? That’s more complicated. One of the concerns is that telomerase can convert healthy cells into indefinitely dividing malignant ones, causing cancer.
“I think that’s still an issue with telomerase. I would not sugar-coat that,” said Church. “So I’m not sure it is time for that just yet, but it’s close. It’s extremely close.”
The news about addiction — rising rates of addiction, record numbers ofoverdose deaths, and the like — tends to be bleak. As clinicians and researchers, however, we have the good fortune to often see its bright side: recovery.
The narrative has long been that substance use disorder is a hopeless condition that few recover from. Grim statistics often thrown around suggest that only a small percentage of people recover from it. Though there’s some truth to that, the problem is that these statistics are never put into context.
There’s no question that many people relapse after an addiction recovery attempt. But most people make multiple attempts. Just as with changing any heavily ingrained habit, like smoking or unhealthy eating, many people don’t succeed on their first try. But many eventually get there with successive tries.
Around 75% of people seeking recovery from a substance use problem achieve their goal, though it may take them some time to achieve full remission. The average number of attempts before success is five, though the median number is just two, meaning that a small number of outliers — usually individuals with the greatest addiction severity and other concomitant mental health issues — who need five-plus attempts, inflate the numbers, making them look worse than they are.
Along with several colleagues, we recently completed a landmark study which, for the first time, comprehensively surveyed Americans who said they had resolved an alcohol or other drug problem.
Some of what we learned from this survey was indeed disheartening — people who have resolved a substance use problem, for instance, are worse off than the rest of the population in terms of health and employment. But the news wasn’t all bad. In fact, some major positives emerged from this work.
First off, this study found that 22.3 million Americans have overcome an alcohol or other drug problem — that’s 9% of U.S. adults at the time we did the survey! That nearly 1 in 10 U.S. adults have overcome a substance use problem is testament to the fact that not only is addiction recovery possible, it’s common. To further contextualize this finding, in the year these data were collected (2015), there were more people who endorsed having resolved an alcohol or other drug problem in the U.S. than had an active alcohol or other drug use disorder (22.3 million vs. 20.8 million).
We also saw significant improvements in quality of life and a decrease in psychological distress over time in recovery, showing that people and their lives get better after resolving a substance use problem. Just about anyone in addiction recovery will tell you as much, but these findings are important because they provide hard evidence that counter the false narrative about substance use disorder being a hopeless condition.
And it’s not just that well-being improves. We also found that 80% of people who had overcome an alcohol or other drug problem accomplished at least one major achievement associated with self-improvement and family engagement since overcoming a substance use problem — things like getting a new job, completing a university degree, or volunteering. And as you might expect, accruing such achievements was associated with improvements in quality of life and well-being over time.
These results challenge commonly held beliefs about the nature of substance use disorder as a constantly recurring condition with little room for improvement. The reality is that this disorder has a good prognosis and is typified by significant improvement over time in recovery.
Along these lines, we found that more years in recovery were associated with an increasing number of achievements. This likely represents a reciprocal process, with more years in recovery leading to more achievements and better outcomes which, in turn, support continuous recovery. With time, people continue improving their quality of life and achieve things they weren’t able to before.
Starting early appears to be one key to better recovery outcomes. Though addiction recovery is associated with numerous positives regardless of one’s age, data suggest that getting into addiction recovery young, regardless of the severity of an individual’s addiction, is associated with better subsequent global functioning and quality of life.
Taken together, this research stands in stark contrast to the heavy stigma and pessimism surrounding substance use disorder, which dramatically compound the burden of addiction. For many people, they represent a major barrier to seeking help and achieving recovery.
Individuals with addiction are often viewed as unstable and dangerous, and are much less likely to be wanted by others as friends or part of their families compared to people with other mental health conditions. Numerous social and legal barriers also impede individuals’ efforts to rebuild their lives after resolving an alcohol or other drug problem, such as laws preventing people with histories of drug arrest from getting federal loans to go to school, and widespread corporate policies forbidding hiring of people with criminal records, even for nonviolent charges related to drug possession.
At the end of the day, addiction is a highly treatable disorder from which the majority of people eventually recover. And our recent study shows that in spite of numerous legal and social barriers, most individuals in addiction recovery go on to rejoin society and contribute to it in numerous meaningful ways.
It’s time we provided individuals with the resources they need to rebuild their lives in addiction recovery, rather than erecting or maintaining barriers to their success. Doing so benefits not just those seeking addiction recovery, but society as a whole.
David Eddie is a research scientist at the Recovery Research Institute and Center for Addiction Medicine at Massachusetts General Hospital, a clinical psychologist in the Department of Psychiatry at Massachusetts General Hospital, and an assistant professor of psychology at Harvard Medical School. John Kelly is the director of Recovery Research Institute, associate director of the Center for Addiction Medicine, and professor of psychiatry at Harvard Medical School.
Sarepta Therapeutics has disclosed positive data from a small trial of a drug meant to be a more potent successor to its marketed Duchenne muscular dystrophy treatment Exondys 51, announcing Monday the experimental drug resulted in stronger production of a key muscle-building protein that Duchenne patients lack.
Sarepta reported a worrisome side effect alongside treatment, however. Reduced magnesium levels, which can lead to heart damage and seizures, were observed in two of the four patients Sarepta reported data from. Executives said the side effect went away after the patients received oral magnesium, and believe that such supplements can keep the condition from occurring in the future.
The data may help reassure investors that Sarepta can build a sustainable business treating Duchenne even if its most closely watched project, a gene therapy for the rare disorder, disappoints in clinical trials. That gene therapy, called SRP-9001, failed to significantly improve patient motor function in a clinical trial readout in January, although more results are due this year.
Sarepta has built a portfolio of Duchenne medicines by developing treatments that help patients produce a shortened form of the protein dystrophin. The hope is doing so can help slow the progression of the disease, which often leaves patients wheelchair-bound in their teens.
The actual amount of protein each of Sarepta's approved drugs helps to produce, however, is small and it's unclear whether treatment leads to significant functional benefits for patients. The company is hoping that a newer type of technology can boost those results and require less frequent dosing.
Sarepta has a slate of six drugs in development using the newer technology, and its first attempt is a treatment called SRP-5051. The drug is intended for the same patients as Exondys 51 and is administered less frequently. It also may be more potent than Exondys, which is infused once weekly and helps patients produce less than 1% of normal levels of dystrophin.
The data revealed on Monday are from four patients treated with SRP-5051 who received a once monthly infusion of 30 milligrams per kilogram of body weight. Dystrophin levels were measured after the third dose at 12 weeks.
Sarepta reported that dystrophin levels were an average of 6.6% of normal in the four patients, although that number was inflated by one participant who received five doses before getting a muscle biopsy because of COVID-19 related trial disruptions.
Citing research indicating dystrophin levels can rise over time as patients continue treatment, Sarepta executives said they believe SRP-5051 can help patients get to more than 10% of normal dystrophin, which could dramatically alter their disease course.
Those gains will need to be balanced against the side effects Sarepta reported, which were rated as "Grade 4" adverse events, meaning they were serious and potentially life-threatening. While Sarepta executives weren't certain why SRP-5051 caused the side effect, they said on a conference call Monday that the drug may interfere with proteins that transport magnesium across cell membranes.
The problems were resolved with supplements, however, which gives Sarepta confidence they can be handled in clinical practice. RBC Capital Markets analyst Brian Abrahams wrote that the side effect is "potentially manageable in [the] context of severe disease but may garner increased regulatory scrutiny."
Sarepta executives said they plan to discuss the findings with the Food and Drug Administration and other regulatory agencies to help develop a trial that can be used to support approval.
Asked whether this trial would directly compare SRP-5051 with Exondys 51 to determine if the newer drug has any functional benefit for patients, CEO Doug Ingram said, "We'll have a good robust discussion with [the FDA] about things like protocol — the idea of head-to-head is an interesting one. It's certainly one that teams talked about I don't know if we'll end up landing on that or not."
Ingram added that the early-stage clinical trials for the two drugs measured dystrophin at different time points, making a head-to-head trial trickier to design.
Although fever is one of the classic symptoms of early COVID-19, most participants reporting febrile episodes in a large panel survey didn't get tested for the illness, researchers said.
Only 17% of people in the COVID-19 Citizen Science Study who self-reported temperatures higher than 38.0°C (100.4°F) at some point said they had been tested -- and nearly one-third of those hadn't received results within 2 weeks, according to Mark J. Pletcher, MD, MPH, of the University of California San Francisco (UCSF), and colleagues.
A statistical model bumped up that figure somewhat, with an estimated probability for receiving a coronavirus test result within 7 days of 20.5% (95% CI 19.1%-22.0%), reaching 26% by the end of 2 weeks (95% CI not given).
Black participants may have been even less likely to be tested, with an adjusted hazard ratio of 0.59 relative to non-Black/non-Hispanic participants, but this value was not statistically significant, the researchers reported in JAMA Network Open.
The data were based on a total of 3,865 febrile episodes reported by 2,679 participants.
"This cohort study's results suggest systematic underuse of coronavirus testing in patients with febrile illness," Pletcher and colleagues concluded. The findings also could explain why COVID-19 became a much bigger problem for the U.S. than it did in "countries such as China and South Korea," which pursued "a much more aggressive targeted approach to testing and appear to have substantially lower community transmission rates," the researchers wrote.
But why were rates in the Citizen Science Study so low? That remains a mystery.
"Whether this is because of lack of testing availability, knowledge about how to get a test, understanding about the importance of testing, or active avoidance (e.g., to avoid economic hardships associated with isolation and quarantine of contacts if one tests positive) is unclear," Pletcher and co-authors wrote.
Availability may have been a factor, especially early in the pandemic: in April 2020, only 9% of febrile participants said they had gotten a test, and it wasn't much higher in May. Moreover, fully one-third of them didn't receive a result within 2 weeks. By July, testing rates rose to 22% (P<0.001), and a somewhat higher proportion were receiving results. But these metrics didn't improve further through the rest of the study period.
The Citizen Science Study began in Mach 2020, run by UCSF and open to "any adult with a smartphone," according to a press release issued when the study began in March 2020. Participants were recruited by varied means, including advertisements and word of mouth, and thus could not be considered representative of the general population.
About three-quarters were women, but the sample did not skew heavily toward any age group; roughly 40% were 50 and older, and about the same percentage were younger than 40. The vast majority were white, however, with only 41 participants identifying as Hispanic and 183 as Black, preventing Pletcher's group from reaching many conclusions about racial/ethnic differences.
The requirement to be a smartphone user also tilted the sample toward higher socioeconomic status: about three-quarters rated their status as 6 or higher on the 10-point MacArthur scale. The researchers argued that this could mean the low testing rates in their study are actually an overestimate: "[T]his stratum of the U.S. population generally has better access to health care and resources than others, so if testing rates are low in our participants, they are likely even lower in more vulnerable subsets of the population," the team wrote.
Other limitations included that the data were based on unverified self-report, and that roughly 20% of participants reporting febrile episodes did not submit follow-up data on testing.
Disclosures
Pletcher reported no disclosures; one co-author reported owning Apple stock for a period prior to the conduct of the study.
