Clinical laboratories and point-of-care settings may have a new diagnostic test if this novel handheld device and related technology is validated by clinical trials
Efforts to develop breath analyzers that accurately identify viral infections, such as SARS-CoV-2 and Influenza, have been ongoing for years. The latest example is ViraWarn from Opteev Technologies in Baltimore, Maryland, and its success could lead to more follow-up PCR tests performed at clinical laboratories.
“Breath is one of the most appealing non-invasive sample types for diagnosis of infectious and non-infectious disease,” said Opteev in its FDA Pre-EUA application. “Exhaled breath is very easy to provide and is less prone to user errors. Breath contains a number of biomarkers associated with different ailments that include volatile organic compounds (VOCs), viruses, bacteria, antigens, and nucleic acid.”
Further clinical trials and the FDA Pre-EUA are needed before ViraWarn can be made available to consumers. In the meantime, Opteev announced that the CES (Consumer Electronic Show) had named ViraWarn as a 2023 Innovation Award Honoree in the digital health category.
“ViraWarn is designed to allow users an ultra-fast and convenient way to know if they are spreading a dangerous respiratory virus. With a continued increase in COVID-19 and a new surge in RSV and influenza cases, we’re eager to bring ViraWarn to market so consumers can easily blow into a personal device and find out if they are positive or negative,” said Conrad Bessemer (above), Opteev President and Co-Founder, in a news release.
Opteev is a subsidiary of Novatec, a supplier of machinery and sensor technology, and a sister company to Prophecy Sensorlytics, a wearable sensors company.
The ViraWarn breath analyzer uses a silk-based sensor that “traces the electric discharge of respiratory viruses coupled with an artificial intelligence (AI) processor to filter out any potential inaccuracies,” according to the news release.
Here is how the breath analyzer (mouthpiece, attached biosensor chamber, and attached printed circuit board chamber) is deployed by a user, according to the Opteev website:
The user turns on the device and an LED light indicates readiness.
The user blows twice into the mouthpiece.
A carbon filter stops bacteria and VOCs and allows virus particles to pass through.
As “charge carriers,” virus particles have a “cumulative charge.”
Electrical data are forwarded to the AI processor.
The AI processer delivers a result.
Within 60 seconds, a red signal indicates a positive presence of a virus and a green signal indicates negative one.
“The interaction of the virus with a specially designed liquid semiconductive medium, or a solid polymer semiconductor, generates changes in the conductivity of the electrical biosensor, which can then be picked up by electrodes. Such electrical data can be analyzed using algorithms and make a positive or negative call,” explains an Opteev white paper on the viral screening process.
While the ViraWarn breath analyzer can identify the presence of a virus, it cannot distinguish between specific viruses, the company noted. Therefore, a clinical laboratory PCR test is needed to confirm results.
Other Breath Tests
Opteev is not the only company developing diagnostic tests using breath samples.
For clinical laboratory managers and pathologists, Opteev’s ViraWarn is notable in breath diagnostics development because it is a personal hand-held tool. It empowers people to do self-tests and other disease screenings, all of which would need to be confirmed with medical laboratory testing in the case of positive results.
Further, it is important to understand that consumers are the primary target for this novel diagnostic device. This is consistent with investor-funding companies wanting to develop testing solutions that can be used by consumers. At the same time, a device like ViraWarn could be used by clinical laboratories in their patient service centers to provide rapid test results.
Company also launches Amazon Clinic virtual healthcare services and announces it will terminate Amazon Care by end of year
Clinical laboratory leaders and pathologists may understandably struggle to keep abreast of Amazon’s moves in the healthcare space. For years, Amazon has tried to develop medical services that disrupt the US healthcare industry in the same way its digital book business upended traditional book publishing. It is clear that Amazon is heavily investing in healthcare ventures that deliver what it believes are better alternatives to existing primary care, clinical laboratory, and retail pharmacy options.
Now, the Seattle-based global e-commerce company has announced plans to acquire One Medical, a membership-based primary care organization, for $3.9 billion according to a news release.
Headquartered in San Francisco, One Medical has primary care offices in 12 major US markets and offers its members 24/7 virtual care, according to the company’s website.
“We think healthcare is high on the list of experiences that need reinvention,” said Neil Lindsay (above), SVP of Amazon Health Services, in a news release announcing the planned acquisition of One Medical. “We love inventing to make what should be easy easier, and we want to be one of the companies that helps dramatically improve the healthcare experience over the next several years,” he added. However, clinical laboratory leaders have watched Amazon’s efforts to disrupt healthcare come and go. (Photo copyright: Advertising Age/Daniel Berman.)
.
As One Medical Grows, Amazon Launches Virtual Care Clinic
“One Medical’s philosophy is rooted in quality care, patient-centered design, and a smart application of technology,” Greg Hayes, MD, District Medical Director for One Medical, Preston Center, Dallas, told Texas News.
For its part, One Medical, which currently has more than 125 clinic locations, sees opportunity to grow its services as part of Amazon (NASDAQ:AMZN). “Joining Amazon is a tremendous next step in innovating and expanding access to high-quality, high-value healthcare,” said Amir Dan Rubin, One Medical Chief Executive Officer, in a blog post.
One Medical (NASDAQ:ONEM) is the operating name for 1Life Healthcare, Inc., a chain of primary care clinics that has 815,000 members, a 14% increase over last year. According to a news release on the company’s third quarter 2022 financial results, its revenue was $261.4 million, up 73% over the same period last year. More than 8,000 companies and organizations work with One Medical, the company’s website notes.
Meanwhile, Amazon is also launching Amazon Clinic, a virtual health service “that delivers convenient, affordable care for common conditions” to people in 32 states, an Amazon news release states.
Amazon Clinic offers virtual care services for 20 common conditions including allergies, acne, migraines, and urinary tract infections. Patients complete a questionnaire through a message-based portal prior to meeting with clinicians.
Clinical laboratory managers and pathologists will want to note that Amazon Clinic will need medical laboratory testing performed to properly diagnose patients and determine the best treatments. Since Amazon Clinic will be a virtual care service, Amazon can be expected to explore such options as sending collection kits directly to individuals using the virtual care service, allowing them to collect needed samples that can be returned to traditional clinical laboratories for testing. Amazon’s existing courier and delivery service would make it easy for the internet giant to deliver either specimen collection kits or home-test kits to obtain the necessary diagnostic data.
“Amazon Pharmacy and One Medical (once the deal closes) are two key ways we’re working to make care more convenient and accessible. But we also know that sometimes you just need a quick interaction with a clinician for a common health concern. … That’s why today were also introducing Amazon Clinic, a message-based virtual care service,” Amazon said in its news release.
What’s Next for Amazon?
Separately, Amazon announced it will terminate Amazon Care at the end of 2022. Amazon Care is a virtual and in-home care service it launched in 2019.
However, in a 2022 internal email, senior vice president of Amazon Health Services Neil Lindsay said Amazon Care wasn’t a sustainable, long-term solution for its enterprise customers, according to Fierce Healthcare.
“This decision wasn’t made lightly and only became clear after many months of careful consideration,” he said. “Although our enrolled members have loved many aspects of Amazon Care, it is not a complete enough offering for the large enterprise customers we have been targeting and wasn’t going to work long-term.”
Will Amazon Provide Clinical Laboratory Services?
Now that Amazon is set with primary care, pharmacy, and virtual health services, might it next explore medical laboratory testing or other diagnostics relationships?
But this apparently has not slowed Amazon’s drive to gain a foothold in the primary care and virtual health services market. Therefore, clinical laboratory leaders should advance their outreach to healthcare providers who are caring for Amazon employees, customers, and soon patients, in new ways and offer their lab services.
These findings may be useful to clinical laboratory professionals when physicians want guidance in effective treatments for COVID-19 patients, particularly when there are concerns about a rebound of the infection
Drug interactions are a major concern for physicians and clinical laboratories. That is especially true given the push for nearly universal COVID-19 vaccinations and boosters. Now, a study conducted in Denmark may show that the use of Paxlovid as an antiviral drug to treat early SARS-CoV-2 infection could trigger drug-drug interactions (DDI) in some patients.
For clinical laboratory managers, insights into the issues associated with Paxlovid may be useful in helping client physicians diagnose their patients and anticipate possible negative drug reactions where other anti-viral drugs are involved.
Also of interest to medical laboratory leaders is the fact that the federal Centers for Disease Control and Prevention (CDC) in May released a Health Alert Network (HAN) Health Advisory about the potential for COVID-19 rebound after Paxlovid treatment.
COVID-19 Rebound, according to the CDC, “has been reported to occur between two and eight days after initial recovery and is characterized by a recurrence of COVID-19 symptoms or a new positive viral test after having tested negative.”
In an article she penned for STAT, Joan Susan Bregstein, MD (above), a pediatric emergency medicine physician and professor of pediatrics at Columbia University Irving Medical Center in New York, wrote, “Is Paxlovid worth it? The CDC advisory states in black, bold, and no uncertain terms that, despite the risk of rebound COVID, ‘Paxlovid continues to be recommended for early-stage treatment of mild to moderate COVID-19 among persons at high risk for progression to severe disease.’ But the definition of ‘high risk’ in this situation has been a moving target since the first days of COVID-19.” Clinical laboratory leaders can attest to the accuracy of that statement. (Photo copyright: Columbia University.)
Do Anti-Viral Drugs Interact with Other Medications?
Paxlovid is the retail name for a combination of two anti-viral drugs: nirmatrelvir and ritonavir. The medication for COVID-19 was developed by American pharmaceutical company Pfizer (NYSE:PFE) and received Emergency Use Authorization from the US Food and Drug Administration in August of this year.
The drug is taken orally for five days by people who test positive for the SARS-CoV-2 coronavirus to head off disease progression as well as serious illness, according to the CDC advisory.
But a “sizeable proportion” of elderly people are on medications that could interact with Paxlovid, Reuters reported.
“Two oral antiviral drugs—nirmatrelvir/ritonavir (NMV/r) and molnupiravir—have been approved for early outpatient treatment of COVID-19 to prevent severe disease. Ritonavir, contained in NMV/r is known to have significant DDI with several drugs frequently used by the elderly. This communication puts the problem with DDI with oral antiviral COVID-19 treatment into perspective,” the study authors wrote.
Their analysis of prescription data from Denmark residents found “extensive use of drugs likely to interact with NMV/r” as follows:
Anticoagulants (blood thinners): used by 20% of people over age 65 and by 30% of people over 80.
Statins (cholesterol-lowering medications): taken by 15% to 18% of people over 65.
Analgesics (for pain), calcium channel blockers (used to decrease blood pressure in patients with hypertension), or digoxin (used to treat heart conditions): taken by 20% of those studied.
In their paper, the researchers offered guidance to physicians. “Before prescribing NMV/r, the patient’s full medical history, including herbals and over-the-counter and recreational drugs, must be known and co-treatment carefully managed by the treating physician or by a specialist to avoid detrimental effects.”
However, one infectious disease specialist told Scientific American it may just take the elderly who were taking Paxlovid more time to completely get over COVID-19.
“Being of an elderly age and then having other risk factors—like diabetes, heart disease, kidney disease, or some sort of cancer—does put you at higher risk of rebound,” Aditya Shah, MBBS, Mayo Clinic Infectious Disease Physician and Researcher, told Scientific American.
That study’s researchers retrospectively reviewed 92 million electronic health records (EHR) from US patients. They found most people (11,270) had been treated with Paxlovid. However, 2,374 patients took molnupiravir, which also was granted EUA status by the FDA and is marketed as Lagevrio.
That COVID-19-rebound study found:
After nirmatrelvir/ritonavir (Paxlovid) treatment: 3.53% had rebound infections, 2.3% with rebound symptoms, and .44% were hospitalized.
After molnupiravir (Lagevrio) treatment: 5.86% had rebound infections, 3.75% with rebound symptoms, and .84% were hospitalized.
“Patients who took molnupiravir were significantly older and had more comorbidities than those who took Paxlovid,” the researchers wrote. “Results further suggest that rebound was not unique to Paxlovid and may be associated with persistent viral infection in some patients treated with either of these two antivirals. There has been more attention to COVID-19 rebound following Paxlovid treatment than molnupiravir, which may be attributable to more people being treated with Paxlovid,” they concluded.
Clinical Laboratories Can Guide Doctors
In an article she penned for STAT, titled, “Paxlovid Rebound Happens, Though Why and to Whom Are Still a Mystery,” Joan Susan Bregstein, MD, a pediatric emergency medicine physician and professor of pediatrics at Columbia University Irving Medical Center in New York, wrote of COVID-19 rebound, “My emergency medicine physician colleagues are seeing tons of it. Although people tend to think of medical care as something that is certain, it is actually a real-time experiment. Paxlovid, like a lot of COVID-19 care, is a reminder of this.”
Similarly, Mayo Clinic’s Shah acknowledged difficulty in identifying a COVID-19 rebound case. “You need real documentation of three tests—a positive, a negative, a positive—and clear documentation of symptoms—all symptoms gone, symptoms come back,” Shah told Scientific American.
Thus, clinical laboratories play a vital role in diagnosing and treating COVID-19 rebound patients, because that is what clinical labs do: test, document, and report. And as the study of the Danish population pointed out, doctors need guidance as they prescribe oral antivirals to COVID-19 patients who are on other drugs and at possible risk of drug-drug interactions.
Should the device prove effective, it could replace invasive point-of-care blood draws for clinical laboratory testing during patient drug therapy monitoring
What if it were possible to perform therapeutic drug monitoring (TDM) without invasive blood draws using breath alone? Patients fighting infections in hospitals certainly would benefit. Traditional TDM can be a painful process for patients, one that also brings risk of bloodline infections. Nevertheless, regular blood draws have been the only reliable method for obtaining viable samples for testing.
One area of critical TDM is in antibiotic therapy, also known as personalized antibiotherapy. However, for antibiotic therapy to be successful it typically requires close monitoring using point-of-care clinical laboratory testing.
Now, a team of engineers and biotechnologists from the University of Freiburg in Germany have developed a biosensor that can use breath samples to measure antibiotic concentrations present in blood, according to a University of Freiburg press release.
The team’s non-invasive collection method requires no needle sticks and can allow for frequent specimen collections to closely monitor the levels of an antibiotic prescribed for a patient. The biosensor also provides physicians the ability to tailor antibiotic regimens specific to individual patients, a core element of precision medicine.
“Until now researchers could only detect traces of antibiotics in the breath,” said Can Dincer, PhD (above), Junior Research Group Leader at the University of Freiburg, and one of the authors of the study, in the press release. “With our synthetic proteins on a microfluid chip, we can determine the smallest concentrations in the breath condensate and [how] they correlate with the blood values.” Should the breath biosensor prove effective in clinical settings, painful blood draws for clinical laboratory testing at the point of care could become obsolete. (Photo copyright: Conny Ehm/University of Freiburg.)
Can a Breath Biosensor Be as Accurate as Clinical Laboratory Testing?
The University of Freiburg’s biosensor is a multiplex, microfluid lab-on-a-chip based on synthetic proteins that react to antibiotics. It allows the simultaneous measurement of several breath samples and test substances to determine the levels of therapeutic antibiotics in the blood stream.
To perform their research, the University of Freiburg team tested their biosensor on blood, plasma, urine, saliva, and breath samples of pigs that had been given antibiotics. The results the researchers achieved with their device using breath samples were as accurate as standard clinical laboratory testing, according to the press release.
The microfluidic chip contains synthetic proteins affixed to a polymer film via dry film photoresist (DFR) technology. These proteins are similar to proteins used by drug-resistant bacteria to sense the presence of antibiotics in their environment. Each biosensor contains an immobilization area and an electrochemical cell which are separated by a hydrophobic stopping barrier. The antibiotic in a breath sample binds to the synthetic proteins which generates a change in an electrical current.
“You could say we are beating the bacteria at their own game,” said Wilfried Weber, PhD, Professor of Biology at the University of Freiburg and one of the authors of the research paper, in the press release.
Rapid Monitoring at Point-of-Care Using Breath Alone
The biosensor could prove to be a useful tool in keeping antibiotic levels stable in severely ill patients who are dealing with serious infections and facing the risk of sepsis, organ failure, or even death. Frequent monitoring of therapeutic antibiotics also could prevent bacteria from mutating and causing the body to become resistant to the medications.
“Rapid monitoring of antibiotic levels would be a huge advantage in hospital,” said H. Ceren Ates, PhD, scientific researcher at the University of Freiburg and one of the authors of the study in the press release. “It might be possible to fit the method into a conventional face mask.”
Along those lines, the researchers are also working on a project to create wearable paper sensors for the continuous measurement of biomarkers of diseases from exhaled breath. Although still in the development stages, this lightweight, small, inexpensive paper sensor can fit into conventional respiratory masks, according to a University of Freiburg press release.
Other Breath Analysis Devices Under Development
Devices that sample breath to detect biomarkers are not new. Dark Daily has regularly reported on similar developments worldwide.
Thus, University of Freiburg’s non-invasive lab-on-a-chip biosensor is worth watching. More research is needed to validate the effectiveness of the biosensor before it could be employed in hospital settings, however, monitoring and managing antibiotic levels in the body via breath samples could prove to be an effective, non-invasive method of providing personalized antibiotic therapy to patients.
Clinical trials on human breath samples are being planned by the University of Freiburg team. This type of precision medicine service may give medical professionals the ability to maintain proper medication levels within an optimal therapeutic window.
InspectIR COVID-19 Breathalyzer identifies a chemical signature associated with SARS-CoV-2 in about three minutes with 91.2% sensitivity and 99.3% specificity
One company is hoping that it can make breathalyzers a viable, easier way to screen for SARS-CoV-2. It will soon have the opportunity to learn if consumers will accept this form of screening for COVID-19, as its device recently obtained an Emergency Use Authorization from the FDA.
On April 14, 2022, InspectIR Systems, LLC, of Frisco, Texas, was granted the US Food and Drug Administration’s first-ever emergency use authorization (EUA202006) for a portable breath test device designed to screen for SARS-CoV-2 infection. Clinical laboratories that perform COVID-19 testing will want to compare the high-level sensitivity of this breath test compared to rapid antigen tests currently used for COVID-19 screening.
The device is about the size of a carry-on suitcase. It provides test results in less than three minutes and is currently authorized for use with subjects who are 18 or older.
The FDA’s EUA limits use of the device to “a qualified, trained operator under the supervision of a healthcare provider licensed or authorized by state law to prescribe tests,” the federal agency said. The test “can be performed in environments where the patient specimen is both collected and analyzed, such as doctor’s offices, hospitals, and mobile testing sites.”
The InspectIR COVID-19 Breathalyzer device “is yet another example of the rapid innovation occurring with diagnostic tests for COVID-19,” said Jeffrey Shuren, MD, JD (above), director of the FDA’s Center for Devices and Radiological Health (CDRH), in the news release. A portable device that can identify SARS-CoV-2 infections in a few minutes with 91% specificity may be of great interest to clinical laboratory companies operating COVID-19 popup testing sites around the nation. (Photo copyright: US Food and Drug Administration.)
In granting the authorization, the FDA cited results of a study with 2,409 participants in which the test had sensitivity (correct positive results) of 91.2% and specificity (correct negative results) of 99.3%. “The test performed with similar sensitivity in a follow-up clinical study focused on the Omicron variant,” the agency stated.
“The FDA continues to support the development of novel COVID-19 tests with the goal of advancing technologies that can help address the current pandemic and better position the US for the next public health emergency,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health (CDRH), in the news release.
In its coverage of the EUA, CNET noted that the InspectIR breath test is more sensitive than rapid antigen tests but not as sensitive as PCR tests. The FDA advised that people who receive a positive test result with the InspectIR COVID-19 Breathalyzer should follow up with a PCR molecular test.
How the InspectIR COVID-19 Breathalyzer Works
InspectIR LLC was founded in 2017 by Tim Wing and John Redmond, Forbes reported. Their original goal was to develop a breathalyzer for detection of cannabis or opioid use. However, with the onset of the COVID-19 pandemic, the entrepreneurs decided to adapt the technology into a SARS-CoV-2 diagnostic test.
As described in the FDA’s EUA documents, a subject breathes into the device using a sterilized one-time-use straw. A pre-concentrator collects and concentrates the five targeted VOCs, all from the ketone and aldehyde families of organic compounds. These go to a Residual Gas Analyzer, and an algorithm determines whether the sample contains the chemical signature associated with a SARS-CoV-2 infection.
Redmond told Forbes that the specific mix of VOCs is proprietary. The article notes that Wing, Redmond, and Verbeck have patented the pre-concentrator technology.
The devices are manufactured at a Pfeiffer Vacuum Inc. facility in Indiana. The InspectIR founders told Forbes they expect to produce 100 units per week in a start-up phase with plans to ramp up as sales increase. They also plan to look at applications for other respiratory diseases.
InspectIR has not announced exact pricing, but Time reports that the company will lease the equipment to clients, and that pricing per test will be comparable to rapid antigen tests.
InspectIR’s first breathalyzer device is receiving much positive coverage from the media. Should it prove to effective at spotting COVID-19 at popup testing sites, it may supplant traditional clinical laboratory rapid antigen tests as the screening test of choice.
