Many companies want to adapt consumer wearables to monitor health conditions, including biomarkers tested by medical laboratories
Clinical laboratory managers know that wearable devices for monitoring biophysical functions or measuring biomarkers are becoming more complex and capable thanks to advances in miniaturization, informatics, software, and artificial intelligence machine learning that enable new functions to be developed and proved to be accurate.
In September, Fitbit (NYSE:FIT), took that a step further. The San Francisco-based maker of personal fitness technology, “received 510(k) clearance from the US Food and Drug Administration (FDA), as well as Conformité Européenne (CE marking) in the European Union, for its electrocardiogram (ECG) app to assess heart rhythm for atrial fibrillation (AFib),” according to a press release.
The fact that Google is currently in the process of acquiring Fitbit for $2.1 billion may indicate that wearable devices to help physicians and patients diagnose and monitor health conditions will be big business in the future.
The new ECG app is available on Fitbit Sense (above), an “advanced health smartwatch.” To use the app, wearers place their finger and thumb to the stainless-steel corners on the watch and remain still for 30 seconds. The app analyzes the heart’s rhythm for signs of AFib. Individuals can take readings of their heart rhythm at any time, monitor for irregularities, and save and share the data. (Photo copyright: Fitbit.)
Helping Doctors ‘Stay Better Connected’ to Their Patients
“Helping people understand and manage their heart health has always been a priority for Fitbit, and our new ECG app is designed for those users who want to assess themselves in the moment and review the reading later with their doctor,” said Eric Friedman, Fitbit co-founder and Chief Technology Officer, in the press release.
Prior to submitting the device for approval to regulatory agencies, Fitbit conducted the clinical trial in regions throughout the US to evaluate the device’s ability to accurately detect AFib from normal sinus rhythm and generate ECG traces. The researchers proved that their algorithm was able to detect 98.7% of AFib cases (sensitivity) and was able to accurately identify normal sinus rhythms (specificity) in 100% of the cases.
Venkatesh Raman, MD, interventional cardiologist and Medical Director of the Cardiac Catheterization Lab at 609-bed MedStar Georgetown University Hospital, was Principal Investigator for the clinical study on Fitbit’s ECG app. “Physicians are often flying blind as to the day-to-day lives of our patients in between office visits. I’ve long believed in the potential for wearable devices to help us stay better connected, and use real-world, individual data to deliver more informed, personalized care,” he said in the press release.
“Given the toll that AFib continues to take on individuals and families around the world,” Raman continued, “I’m very enthusiastic about the potential of this tool to help people detect possible AFib—a clinically important rhythm abnormality—even after they leave the physician’s office.”
Fitbit ECG App Receives European CE Marking
In addition to receiving approval for the Fitbit ECG app in the US, the device also received CE marking (Conformité Européenne) for use in some European countries.
In October 2020, the app was made available to Fitbit Sense users in the US, Austria, Belgium, Czech Republic, France, Germany, Ireland, Italy, Luxembourg, the Netherlands, Poland, Portugal, Romania, Spain, Sweden, Switzerland, and the United Kingdom. The device also received approval for use in Hong Kong and India.
It is estimated that more than 33.5 million people globally have AFib, an irregular heart rhythm (arrhythmia) that can lead to stroke, blood clots, or heart failure. The American Heart Association estimates that at least 2.7 million Americans currently live with the condition. The most common symptoms experienced by those with the condition are:
Irregular heartbeat,
Heart palpitations (rapid, fluttering, quivering or pounding),
Lightheadedness,
Extreme fatigue,
Shortness of breath, and
Chest pain.
Risk factors for AFib include advancing age, high blood pressure, obesity, diabetes, European ancestry, hyperthyroidism, chronic kidney disease, alcohol use, smoking, and known heart issues such as heart failure, ischemic heart disease, and enlargement of the chambers on the left side of the heart.
According to the Centers for Disease Control and Prevention (CDC), there are more than 454,000 hospitalizations annually in the US that list AFib as the primary diagnosis. In 2018, AFib was mentioned on 175,326 death certificates with the condition being the underlying cause of death in 25,845 of those cases.
The CDC reports that cases are increasing and projects that by 2030 12.1 million people in the US will have AFib. Many people are asymptomatic of the illness and do not know they have it, which can make AFib more difficult to diagnose.
“Early detection of AFib is critical, and I’m incredibly excited that we are making these innovations accessible to people around the world to help them improve their heart health, prevent more serious conditions, and potentially save lives,” Friedman said, in a statement.
Clinical laboratory managers should monitor these developments closely. Fitbit’s FDA clearance and CE Marking of its ECG app suggest this trend is accelerating.
Abbott sends the SARS-CoV-2 test results directly to patients’ smartphones, which can be displayed to gain entrance into areas requiring proof of COVID-19 testing
There is no greater example that COVID-19 is a major force for change in the clinical laboratory industry than the fact that—though the US federal government pays 50% of the nation’s total annual healthcare spend of $3.5 trillion—it recently spent $760 million to purchase 150 million COVID-19 tests from Abbott Laboratories (NYSE:ABT), an American multinational medical devices and healthcare company headquartered in Abbott Park, Ill., “to expand strategic, evidence-based testing in the United States,” according to the company’s website.
In August, the federal Food and Drug Administration (FDA) granted an emergency use authorization (EUA) to Abbott for its BinaxNOW portable rapid-response COVID-19 antigen (Ag) test. The credit-card sized test costs $5 and can return clinical laboratory test results in minutes, rather than hours, days, or in some cases, weeks, the Wall Street Journal (WSJ) reported.
The test includes a free smartphone app called NAVICA, which enables those tested to receive their test results directly on their mobile devices—bypassing the patient’s primary care physicians.
According to Abbott’s website, the app “allows people who test negative to get an encrypted temporary digital NAVICA Pass, similar to an airline boarding pass. NAVICA-enabled organizations will be able to verify an individual’s negative COVID-19 test results by scanning the individual’s digital NAVICA Pass to facilitate entry into facilities.”
This feature of Abbott’s new COVID-19 test is a good example of how quickly innovation in the medical laboratory testing profession is bringing new features and new capabilities to the marketplace. By marrying the SARS-CoV-2 test with the NAVICA Pass feature, Abbott hopes to deliver increased value—not just to physicians and their patients—but also to employers with employee screening programs and federal government programs designed to screen federal employees, as well as being used for screening travelers at airports and other transportation hubs.
Abbott appears to be banking that in the future such identification will be required to “enter organizations and other places where people gather,” as the company’s website states.
Testing Limited to CLIA-Certified Clinical Laboratories
An HHS news release announcing the government’s planned distribution of the BinaxNOW tests stated that “Testing will be potentially deployed to schools and to assist with serving other special needs populations.”
In the news release, Alex Azar, HHS Secretary, said, “By strategically distributing 150 million of these tests to where they’re needed most, we can track the virus like never before and protect millions of Americans at risk in especially vulnerable situations.”
The EUA adds that “Testing of nasal swab specimens using [BinaxNOW] … is limited to laboratories certified under CLIA that meet the requirements to perform high, moderate, or waived complexity tests. This test is authorized for use at the [point of care], i.e., in patient care settings operating under a CLIA Certificate of Waiver, Certificate of Compliance, or Certificate of Accreditation.”
The FDA’s EUA describes the BinaxNOW portable rapid-response COVID-19 antigen test (above) as “a lateral flow immunoassay intended for the qualitative detection of nucleocapsid protein antigen from SARS-CoV-2 in direct nasal swabs from individuals suspected of COVID-19 by their healthcare provider within the first seven days of symptom onset.” The test costs $5 and Abbott sends results directly to the patient’s smartphone using the free NAVICA app included with the test. (Photo copyright: Abbott Laboratories.)
IVD Companies See Boom in COVID-19 Test Sales
Demand for COVID-19 testing has created opportunities for in vitro diagnostics (IVD) companies that can develop and bring tests to market quickly.
Recent issues of Dark Daily’s sister print publication—The Dark Report (TDR)—covered IVD companies’ second quarter (Q2) boom in sales of COVID-19 instruments and tests, while also noting a fall-off in routine clinical laboratory testing during the COVID-19 pandemic.
Abbott Laboratories saw molecular diagnostics sales increase 241% in Q2 driven by $283 million in sales of COVID-19 testing, while rapid diagnostic COVID-19 testing rose 11% on $180 million in sales in Q2, TDR reported, based on Abbott data.
“There is huge economic incentive for diagnostic companies to develop technologies that can be used to create rapid tests that are cheap to perform,” said Robert Michel, Publisher and Editor-in-Chief of TDR and Dark Daily. “In this sense, COVID is a major force for change.”
“This new COVID-19 antigen test is an important addition to available tests because the results can be read in minutes, right off the testing card,” said Jeff Shuren, MD, JD (above), Director of the FDA’s Center for Devices and Radiological Health (CDRH), in an FDA news release announcing the federal government’s $760 million purchase of 150 million Abbott BinaxNOW rapid-response antigen COVID-19 tests. “This means people will know if they have the virus in almost real-time. Due to its simpler design and the large number of tests the company anticipates making in the coming months, this new antigen test is an important advancement in our fight against the pandemic.” (Photo copyright: The New York Times.)
Thus, Abbott is determined to ensure this product launch is successful and that the test works as promised. According to a news release, “In data submitted to the FDA from a clinical study conducted by Abbott with several leading US research universities, the BinaxNOW COVID-19 Ag Card demonstrated sensitivity of 97.1% (positive percent agreement) and specificity of 98.5% (negative percent agreement) in patients suspected of COVID-19 by their healthcare provider within the first seven days of symptom onset.”
“The massive scale of this test and app will allow tens of millions of people to have access to rapid and reliable testing,” said Joseph Petrosino, PhD, professor and chairman, Molecular Virology and Microbiology, Baylor College of Medicine, in the Abbott news release. “With lab-based tests, you get excellent sensitivity but might have to wait days or longer to get the results. With a rapid antigen test, you get a result right away, getting infectious people off the streets and into quarantine so they don’t spread the virus.”
Abbott has invested hundreds of millions of dollars in two manufacturing facilities where the tests will be made, John Hackett Jr, PhD, an immunologist and Abbott’s Divisional Vice President Applied Research and Technology, and lead scientist on the BinaxNOW project, told The Atlantic.
“Our nation’s frontline healthcare workers and clinical laboratory personnel have been under siege since the onset of this pandemic,” said Charles Chiu, MD, PhD, professor of Laboratory Medicine at University of California, San Francisco, in the Abbott news release. “The availability of rapid testing for COVID-19 will help support overburdened laboratories, accelerate turnaround times, and greatly expand access to people who need it.”
However, other experts are not so sure. In the Atlantic article, Michael Mina MD, PhD, Assistant Professor Epidemiology at Harvard’s T.H. Chan School of Public Health, voiced the need to test both asymptomatic and pre-symptomatic people. “This is the type of [COVID-19] test we have been waiting for—but may not be the test.”
Nevertheless, the federal government’s investment is significant. Abbott plans to start shipping tens of millions of tests in September and produce 50 million tests per month starting in October, Forbes reported.
Shifting Clinical Laboratory Paradigms
BinaxNOW will be performed without doctors’ orders, in a variety of locations, and results go directly to patients’ smartphone—without a pathologist’s interpretation and medical laboratory report. This is new ground and the impact on non-CLIA labs, and on healthcare in general, is yet to be seen.
Clinical laboratory managers will want to monitor the rise of rapid-response tests that can be easily accessed, conducted, and reported on without physician input.
Amazon’s app-based employee healthcare service could be first step toward retailer becoming a disruptive force in healthcare; federal VA develops its own mHealth apps
More consumers are using smartphone applications (apps) to manage different aspects of their healthcare. That fact should put clinical laboratories and anatomic pathology groups on the alert, because a passive “wait and see” strategy for making relevant services and lab test information available via mobile apps could cause patients to choose other labs that do offer such services.
Patient use of apps to manage healthcare is an important trend. In January, Dark Daily covered online retail giant Amazon’s move to position itself as a leader in smartphone app-based healthcare with its launch of Amazon Care, a virtual medical clinic and homecare services program. At that time, the program was being piloted for Seattle-based employees and their families only. Since then, it has been expanded to include eligible Amazon employees throughout Washington State.
Mobile health (mHealth) apps are giving healthcare providers rapid access to patient information. And healthcare consumers are increasingly turning to their mobile devices for 24/7 access to medical records, clinical laboratory test results, management of chronic conditions, and quick appointment scheduling and prescription refills.
Thus, hearing ‘There’s an app for that’ has become part of patients’ expectations for access to quality, affordable healthcare.
For clinical laboratory managers, this steady shift toward mHealth-based care means accommodating patients who want to use mobile apps to access lab test results and on-demand lab data to monitor their health or gain advice from providers about symptoms and health issues.
Amazon, VA, and EMS Develop Their Own mHealth Apps
The Amazon Care app can be freely downloaded from Apple’s App Store and Google Play. With it, eligible employees and family members can:
Communicate with an advice nurse;
Launch an in-app video visit with a doctor or nurse practitioner for advice, diagnoses, treatment, or referrals;
Request a mobile care nurse for in-home or in-office visits;
Receive prescriptions through courier delivery.
The combination telehealth, in-person care program, mobile medical service includes dispatching nurses to homes or workplaces who can provide “physical assessments, vaccines or common [clinical laboratory] tests.”
“Amazon is a company that is experimenting a lot with a variety of opportunities in healthcare,” Glen Tullman (above), Executive Chairman of Livongo, a healthcare company specializing in treating diabetes, and an Amazon partner company, told CNBC. “It’s one to watch.” (Photo copyright: CNBC.)
However, the US federal Department of Veterans Affairs (VA) also is becoming a major player in the mHealth space with the development of its own mobile app—VA Launchpad—which serves as a portal to a range of medical services.
Veterans can access five categories of apps that allow them to manage their health, communicate with their healthcare team, share health information, and use mental health and personal improvement tools.
“The VA was an early adopter of digital health tools and remains a leader within US healthcare in leveraging technology to enhance patient engagement,” Neil C. Evans, MD (above), Chief Officer in the VA Office of Connected Care, told Healthcare IT News. “These digital tools are allowing veterans to more actively understand their health data, to better communicate with VA clinical teams, and to engage more productively as they navigate their individual health journeys,” Evans added. (Photo copyright: Department of Veterans’ Affairs.)
mHealthIntelligence reported that mobile health tools also are enabling first responders to improve emergency patient care. At King’s Daughters Medical Center in Brookhaven, Miss., emergency medical technicians (EMTs) are using a group of mHealth apps from DrFirst called Backline to gain real-time access to patients’ HIPAA-compliant medication histories, share clinical data, and gain critical information about patients prior to arriving on the scene.
Using Backline, EMTs can scan the barcode on a patient’s driver’s license to access six months’ worth of medication history.
“In the past, we could only get information from [patients] who are awake or are willing to give us that information,” Lee Robbins, Director of Emergency Medical Services at King’s Daughters Medical Center in Brookhaven, Miss., told mHealthIntelligence. “Knowing this information gives us a much better chance at a good outcome.”
Smartphone App Detects Opioid Overdose
The opioid crisis remains one of the US’ greatest health challenges. The federal Centers for Disease Control and Prevention (CDC) reported 47,600 opioid-related deaths in 2017, and the problem has only gotten worse since then.
To curtail these tragic deaths, University of Washington (UW) researchers developed a smartphone app called Second Chance, that they believe can save lives by quickly diagnosing when an opioid overdose has occurred.
The app uses sonar to monitor an opioid user’s breathing rate and, according to a UW press release, can detect overdose-related symptoms about 90% of the time from up to three feet away. The app then contacts the user’s healthcare provider or emergency services.
The UW researchers are applying for US Food and Drug Administration (FDA) clearance. They published their findings in the journal Science Translational Medicine.
While Demand for mHealth Apps Grows, Concern over Privacy and Security also Increases
According to mobile data and analytics company App Annie, global downloads of medical apps grew to more than 400 million in 2018, up 15% from two years earlier.
“As with mobile banking, consumers are showing they trust mobile apps with their most sensitive information and are willing to leverage them to replace tasks traditionally fulfilled in-person, such as going into a bank branch or, in the case of medical apps, to a doctor’s office,” App Annie’s website states.
However, the proliferation of mHealth apps has raised privacy and safety concerns as well. While the FDA does regulate some mobile health software functions, it does not ensure an mHealth app’s accuracy or reliability.
Fierce Healthcarereported that federal lawmakers are worried veterans who use the VA’s 47 mHealth apps could find their sensitive healthcare information shared or sold by third-party companies. In fiscal year 2018, veterans participated in more than one million video telehealth visits, a VA press release reported.
US Rep. Susie Lee, D-Nevada, Chairperson of the House Veterans’ Affairs Subcommittee on Technology Modernization, told Fierce Healthcare, “As we assess the data landscape at the VA and the larger health IT space, we need to look at where protections exist or don’t exist and whether we need more guardrails.”
What does all this mean for clinical laboratories? Well, lab managers will want to keep an eye on the growing demand from consumers who want direct access to laboratory test data and appointment scheduling through mHealth apps. And, also be aware of HIPAA regulations concerning the sharing of that information.
Pooled testing could become a critical tool for clinical laboratories to spot the SARS-CoV-2 coronavirus among asymptomatic and pre-symptomatic individuals
COVID-19 testing for individuals has expanded in the US, but the number of people actually tested remains a small proportion of the country’s total population and clinical laboratory testing supply shortages continue to hamper progress. A technique known as pooled testing may help. Federal experts hope it will substantially increase the number of individuals who are tested for the SARS-CoV-2 coronavirus before it makes a possible resurgence in the fall.
One-by-one, some of the nation’s largest clinical laboratory organizations are developing the capability to do pooled testing. For example, on July 18, the Food and Drug Administration (FDA) announced it had issued Quest Diagnostics (NYSE:DGX) an Emergency Use Authorization (EUA) for its SARS-CoV-2 rRT-PCR test, and that it is valid for up to four individual samples as a pooled test.
Quest’s rRT-PCR test was the first COVID-19 diagnostic test to be authorized for use with pooled samples, the FDA noted in a new release.
In the FDA’s statement announcing Quest’s EUA for its rRT-PCR test, Stephen M. Hahn, MD (above), FDA Commissioner, said, “This EUA for sample pooling is an important step forward in getting more COVID-19 tests to more Americans more quickly while preserving testing supplies.” He added, “Sample pooling becomes especially important as infection rates decline and we begin testing larger portions of the population.” (Photo copyright: CBS News.)
Following the announcement of Quest’s EUA, on July 24 the FDA announced LabCorp’s (NYSE:LH) EUA for its COVID-19 real-time reverse transcription polymerase chain reaction (rRT-PCR) test. The test, the EUA states, is intended for the “qualitative detection of nucleic acid from SARS-CoV-2 in upper and lower respiratory specimens” in individuals suspected of COVID-19, using “a matrix pooling strategy (i.e., group pooling strategy), containing up to five individual upper respiratory swab specimens (nasopharyngeal, mid-turbinate, anterior nares or oropharyngeal swabs) per pool and 25 specimens per matrix.”
Exponentially Increasing Testing
In pooled testing, instead of performing a coronavirus test on every specimen received by a clinical laboratory, samples from each individual specimen are taken and then combined with samples from other specimens. A single test is then performed on the entire collection of specimen samples.
If the results of the pooled samples are negative for coronavirus, it is safe to assume that all the specimens in the batch are negative for the virus. If the pooled sample comes back positive, then it will be necessary to go back to the original specimens in that pooled sample and test each specimen individually.
In an exclusive interview with Dark Daily’s sister print publication The Dark Report, Steven H. Hinrichs, MD, Chair of the Department of Pathology and Microbiology at the University of Nebraska Medical Center (UNMC), noted that one pitfall of pooled testing is that it works best in areas of low virus prevalence.
“For pooled testing, the ideal level of low prevalence would be an infection rate below 10%,” he said, adding, “For COVID-19 test manufacturers, pooled testing has the potential to reduce the number of standard tests labs run by roughly 40% to 60%, depending on the population being tested.
“Cutting the number of COVID-19 tests would be a disadvantage for test manufacturers, because pooled tests would identify large numbers of uninfected individuals who would not require standard testing with EUA tests.
“On the other hand, this policy would be a significant advantage for US labs because pooled testing would cut the number of standard tests,” he continued. “Clinical labs would save money on tests, reagents, and other supplies. It would also ease the burden on the lab’s technical staff,” Hinrichs concluded.
“In our study, we show that it’s reasonable to pool five samples, although we realized that some people may want to pool 10 samples at once,” noted Hinrichs. “But even if one sample is positive in a pool of five, then testing five samples at once saves 80% of our costs if all of those samples are negative. But, if one sample is positive, each of those five samples needs to be retested using the standard test,” Hinrichs explained.
During an American Society for Microbiology (ASM) virtual conference, Deborah Birx, MD, White House Coronavirus Response Coordinator, said, “Pooling would give us the capacity to go from a half a million tests per day to potentially five million individuals tested per day,” STAT reported.
Advantages of using pooled testing for the coronavirus include:
Expanding the number of individuals tested,
Stretching laboratory supplies, and
Reducing the costs associated with testing.
Health officials believe that individuals who have COVID-19 and are asymptomatic are largely responsible for the rising number of coronavirus cases in the US, STAT reported.
“It allows you to test more frequently in a population that may have a low prevalence of disease,” Benjamin Pinsky, MD, PhD, Associate Professor, Departments of Pathology and Medicine at Stanford University School of Medicine, told STAT. “That would allow you to test a lot of negatives, but also identify individuals who are then infected, before they develop symptoms.”
Pooled testing also could be advantageous for communities where COVID-19 is not prevalent, in neighborhoods that need to be tested during an outbreak, and for schools, universities, organizations, and businesses that want to remain safely open while periodically monitoring individuals for the virus, CNN reported.
“The goal is to increase the capacity of testing in a relatively straightforward fashion,” Pinsky told STAT. “The caveat is that by pooling the sample, you’re going to reduce the sensitivity of the test.”
According to Pinsky, “pooling only makes sense in places with low rates of COVID-19, where you expect the large majority of tests to be negative. Otherwise, too many of the pools would come back positive for it to work as a useful surveillance tool,” STAT reported.
As Clinical Lab Testing Increases, Pooled Testing for COVID-19 Could Be Critical
Pooled testing has been used in other countries, including China, to test larger amounts of people for COVID-19.
“If you look around the globe, the way people are doing a million tests or 10 million tests is they’re doing pooling,” Birx said during the ASM virtual conference, CNN reported.
In a press release, the American Clinical Laboratory Association (ACLA) stated that about 300,000 tests for COVID-19 were performed per day in labs across the US in late June. That number was up from approximately 100,000 tests being performed daily in early April.
“All across the country, clinical laboratories are increasing the number of labs processing tests, purchasing additional testing platforms, and expanding the number of suppliers to provide critical testing materials,” said Julie Khani, ACLA President in the press release. “However, the reality of this ongoing global pandemic is that testing supplies are limited. Every country across the globe is in need of essential testing supplies, like pipettes and reagents, and that demand is likely to increase in the coming months.”
Clinical laboratory managers will want to keep an eye on these developments. As the need for COVID-19 testing increases, pooled testing may provide an efficient, cost-effective way to spot the coronavirus, especially among those who are asymptomatic or pre-symptomatic and who display no symptoms.
Pooled testing could become a critical tool in the diagnosis of COVID-19 and potentially decrease the overall number of deaths.
Study scientists identified several currently available drugs that could inhibit growth of these “streaming filaments,” which infected cells use to go after non-infected cells
Like a scene from a bad horror movie, scientists have discovered that SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, may be even more sinister and macabre than previously thought. The new research findings will interest those pathologists and clinical laboratory professionals who want to understand how the coronavirus spreads once it enters the body.
Headed by scientists from the University of San Francisco (UCSF), a team of international researchers discovered that “when the SARS-CoV-2 virus infects a human cell, it sets off a ghoulish transformation,” reported the Los Angeles Times (LA Times).
“Obeying instructions from the virus,” the LA Times continued, “the newly infected cell sprouts multi-pronged tentacles studded with viral particles. These disfigured zombie cells appear to be using those streaming filaments, or filopodia, to reach still-healthy neighboring cells. The protuberances appear to bore into the cells’ bodies and inject their viral venom directly into those cells’ genetic command centers—thus creating another zombie.”
As If the Coronavirus Weren’t Bad Enough!
“It’s just so sinister that the virus uses other mechanisms to infect other cells before it kills the cell,” Nevan Krogan, PhD, Professor, Department of Cellular Molecular Pharmacology at the UCSF School of Medicine, one of the study’s authors, told the LA Times.
The images above taken with an electron microscope show the streaming filaments—or as the researchers described in their published study, “filopodial protrusions possessing budding viral particles”—reaching out from cells infected with the SARS-CoV-2 coronavirus looking for other cells to infect. (Photos copyright: Los Angeles Times/Elizabeth Fischer, MA, Chief, RML Microscopy Unit, NIAID/NIH.)
SARS-CoV-2 Has Evolved, Study Suggests
Prior to this discovery, scientists believed that the coronavirus infected cells in a typical fashion by finding receptors on the surface of cells lining an individual’s mouth, nose, respiratory tract, lungs or blood vessels, and eventually replicating and invading larger cells. However, this new research may suggest that the virus has evolved and developed new ways to pass quickly and effectively from cell to cell.
While some other illnesses, including smallpox, human immunodeficiency virus (HIV), and some influenza viruses have been known to use filopodia to enhance their ability to infect cells, Krogan contends that those other viruses do not seem to have the prolific growth of the SARS-CoV-2 filopodia.
“By conducting a systematic analysis of the changes in phosphorylation when SARS-CoV-2 infects a cell, we identified several key factors that will inform not only the next areas of biological study, but also treatments that may be repurposed to treat patients with COVID-19,” he said, in a UCSF news release.
UCSF Study Identifies Drugs, Compounds That May Disrupt Growth of Filopodia
One key finding is that the coronavirus was utilizing a specific type of molecule from a family of cellular helpers known as Kinase to create the filopodia.
The researchers conducted a “quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells,” the study noted, which revealed a “dramatic rewiring of phosphorylation on host and viral proteins.
“SARS-CoV-2 infection promoted casein kinase 2 (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest,” the study continued, adding, “Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles.
“Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies,” the researchers concluded.
To determine if they might be helpful in combating COVID-19, the UCSF research team tested drugs and compounds that were either already cleared to market by the US federal Food and Drug Administration (FDA), in clinical trials, or under preclinical development.
After discovering the Kinase connection, the scientists focused on specialized drugs known as Kinase inhibitors.
“We narrowed in on about a dozen, and we highlighted about six or seven that look particularly potent in a laboratory setting,” Krogan told ABC News. “And we’re very excited now to try and take these into clinical trials.”
Among the drugs the study identified as potentially being able to disrupt the creation of filopodia and slow the spread of COVID-19 in the body are:
Silmitasertib: A drug that is currently in the clinical trial stages as a treatment for bile duct cancer and other cancers, including hematological and lymphoid malignancies;
“We are encouraged by our findings that drugs targeting differentially phosphorylated proteins inhibited SARS-CoV-2 infection in cell culture,” said Kevan Shokat, PhD, Professor of Cellular and Molecular Pharmacology at UCSF, and co-author of the study, in the UCSF news release. “We expect to build upon this work by testing many other kinase inhibitors, while concurrently conducting experiments with other technologies to identify underlying pathways and additional potential therapeutics that may intervene in COVID-19 effectively.”
Presently, the UCSF study provides no direct benefit to COVID-19 illness patients or clinical laboratories performing SARS-CoV-2 testing. However, that could change rapidly. Pathologists and medical laboratory managers will want to keep an eye on this research, because it may lead to new treatments for COVID-19 that would require increased clinical laboratory testing to identify people infected with the coronavirus.
