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.
Understanding how superspreading occurs can help clinical lab leaders slow and even prevent the spread of SARS-CoV-2 within their communities and health systems
Clinical laboratories understand the critical importance of preventing the spread of infection. However, according to the Boston Globe, researchers worldwide are learning that roughly 80% of new COVID-19 cases are caused by just 10% of infected people. Those people are called superspreaders.
It’s critical that medical laboratory managers are aware of the role superspreaders play in transmitting SARS-CoV-2, the coronavirus that causes the COVID-19 illness.
Clinical lab leaders who understand how superspreading occurs can take steps to protect staff, patients, and anyone who visits the facility. Because lab personnel such as couriers and phlebotomists, among others, come into contact with large numbers of people daily, understanding how to identify superspreaders could limit transmissions of the coronavirus within the laboratory, as well as within hospital networks.
Superspreading versus Plodding
Influenza and other viruses tend to spread in a way that epidemiologists call “plodding.” One person infects another, and the virus slowly spreads throughout the population. However, scientists around the globe are finding that SARS-CoV-2 transmission does not fit that pattern. Instead, a few infected people appear to be transmitting the virus to dozens of other people in superspreading events, Boston Globe reported.
“You can think about throwing a match at kindling. You throw one match, it might not light the kindling. You throw another match, it may not light the kindling. But then one match hits the right spot and all of a sudden the fire goes up,” Ben Althouse, PhD, principal scientist and co-chair of epidemiology at the Institute for Disease Modeling in Bellevue, Wash., told the Boston Globe.
But because roughly 90% of infected people aren’t spreading the virus, identifying who the superspreaders are can be a challenge. Nevertheless, limiting situations in which superspreading is likely to occur could greatly reduce the spread of infection.
Samuel Scarpino, PhD (above), Assistant Professor in the Network Science Institute at Northeastern University, says that “preventing superspreader events could go a long way toward stopping COVID-19,” Scientific American reported. “All of the data I’m seeing so far suggest that if you tamp down the superspreader events, the growth rate of the infections stops very, very quickly,” Scarpino said. (Photo copyright: University of Vermont.)
Examples of Superspreading Events
One of the first big outbreaks in the United States was an example of a superspreading event. The Biogen (NASDAQ:BIIB) leadership conference in late February in Boston resulted in at least 99 cases of COVID-19 just in Massachusetts, reported the Boston Globe.
Several superspreading events have occurred in houses of worship. One well-documented example prompted a CDC Morbidity and Mortality Weekly Report, titled, “High SARS-CoV-2 Attack Rate Following Exposure at a Choir Practice—Skagit County, Washington.” The 122-member choir met for practice twice in March. On March 3 no one had symptoms, but one person had cold-like symptoms at the March 10 practice. Eventually, 53 members tested positive for SARS-CoV-2.
On May 30, a Texas family held a birthday party, Medical Xpress reported. Twenty-five people attended the party, which only lasted a few hours. The family followed the state’s guidelines for gatherings, however one of the hosts was infected with the SARS-CoV-2 coronavirus and wasn’t aware of it. Seven attendees contracted it, and those seven spread the virus to an additional 10 family members. A total of 18 members of a single family were infected.
There are commonalities among the documented superspreading events. Most occur indoors, often in poorly ventilated areas. Some activities cause more respiratory droplets to be expelled than others, such as singing. Some respiratory droplets are released simply by breathing, and many more are expelled when a person talks. Talking louder expels even more droplets into the air.
Are Some People More Likely to Spread the Coronavirus than Others?
The fact that so few people are responsible for the majority of transmissions of the virus raises questions. Do some people simply have more virus particles to shed? Is biology a factor?
One factor may be how long the SARS-CoV-2 coronavirus is in the body before symptoms of the COVID-19 illness manifest.
“If people got sick right away after they were infected, they might stay at home in bed, giving them few opportunities to transmit the virus,” noted Scientific American in “How ‘Superspreading’ Events Drive Most COVID-19 Spread.” However, CDC states on its website that “The incubation period for COVID-19 is thought to extend to 14 days, with a median time of 4-5 days from exposure to symptoms onset. One study reported that 97.5% of persons with COVID-19 who develop symptoms will do so within 11.5 days of SARS-CoV-2 infection.”
During that time, infected individuals may transmit the virus to dozens of other people. The CDC estimates that about 40% of transmission occurs in pre-symptomatic people, Scientific American reported.
But it’s not all bad news. The fact that circumstances may be more important than biology might be good news for clinical laboratories. “Knowing that COVID-19 is a superspreading pandemic could be a good thing. It bodes well for control,” Nelson told the Boston Globe.
Clinical laboratory managers are encouraged to follow CDC recommended safety protocols, titled, “Guidance for General Laboratory Safety Practices during the COVID-19 Pandemic.” They include social distancing, setting up one-way paths through lab areas, sanitizing shared surfaces such as counters and benchtops, and implementing flexible leave policies so that sick employees can stay home.
Following these guidelines, and being aware of superspreaders, can help medical laboratories and anatomic pathology groups keep staff and customers free of infection.
Researchers from multiple countries looked at sewage samples collected from 2018 through early 2020, with findings that may interest microbiologists and medical laboratory scientists
Clinical laboratory tests for the SARS-CoV-2 coronavirus can identify COVID-19 cases in individuals. But in multiple countries, researchers have tested untreated sewage for remnants of the pathogen, and some scientists have arrived at a surprising but unconfirmed theory—that the coronavirus appeared in Europe long before the first reported cases in Wuhan, China.
In an article for The Conversation, titled, “Coronavirus: Wastewater Can Tell Us Where the Next Outbreak Will Be,” Davey Jones, PhD, Professorial Chair of Soil and Environmental Science at Bangor University in the UK, wrote, “For the past three months, we have been using a test called polymerase chain reaction (PCR) to find traces of SARS-CoV-2 in untreated wastewater. We believe this could form a valuable part of disease surveillance. Most UK towns and cities are served by just one or two wastewater treatment works, so a single sample—about a liter of water—can provide information on millions of people.”
The Lancet reported on similar research being conducted in Barcelona, Spain. At the University of Barcelona (UB) researchers analyzed raw sewage samples taken between April 13 and May 25 from two large wastewater treatment plants in the city. In addition, they analyzed frozen archival samples taken from one of the plants in 2018 (January-March), 2019 (January, March, September-December), and 2020 (January-March).
They reported presence of the virus in samples taken as early as Jan. 15, 2020, 41 days before the Barcelona’s first known case was reported on Feb. 25. Most surprisingly, they reported the presence of two genetic fragments—IP2 and IP4—in a sample taken on March 12, 2019.
That would seem to conflict with early reports that the first human infections occurred in Wuhan, China, in November to December of 2019.
All other Barcelona samples from 2018 and 2019, with the exception of one, tested negative, said Albert Bosch, PhD, in a press release. Bosch is professor at the Faculty of Biology at UB, head of the Enteric Virus laboratory at UB, president of the Spanish Society of Virology, and one of the lead study’s researchers. In the March 12 sample, he said, “the levels of SARS-CoV-2 were low but were positive, using two different targets.”
Scientists all over the world, like those seen above in China, are testing sewer wastewater looking for remnants of the SARS-CoV-2 coronavirus, following multiple reports from several countries suggesting that the COVID-19 pandemic may not have originate at the Wuhan, China, market. (Photo copyright: The Telegraph.)
Similar Findings in Brazil and Italy
Researchers in Brazil and Italy also have reported the early presence of SARS-CoV-2 in wastewater samples.
In northern Italy, researchers tested samples taken from five wastewater plants between October 2019 and February 2020 and reported positive test results in samples taken on December 18 in Milan and Turin. The country’s first case of COVID-19 was documented on Feb. 21. Those findings were published June 26 on medRxiv, titled, “SARS-CoV-2 Has Been Circulating in Northern Italy Since December 2019: Evidence from Environmental Monitoring.” The study has not been peer reviewed.
Researchers in Florianópolis, Brazil, tested wastewater samples taken between late October and early March. They reported presence of the virus in two samples from Nov. 27, 2019. Those findings, also not peer-reviewed, were published June 29 on medRxiv.
Questioning China Origins
The findings from Spain and Italy led Oxford University epidemiologist Tom Jefferson, MD, Honorary Senior Research Fellow, Center For Evidence Based Medicine, to speculate that the SARS-CoV-2 virus did not originate in China. “I think the virus was already here—here meaning everywhere,” he told The Telegraph. “We may be seeing a dormant virus that has been activated by environmental conditions.”
He repeated his assertions in an interview with CGTN, an English-language news channel controlled by the Chinese government. “We know that for certain it was recognized as a newly identified disease in Wuhan,” he said. “I think there’s little doubt about that. But being newly identified in Wuhan and being originated from Wuhan are two different things. It’s not necessarily cause and effect.”
In addition to questioning the origins of the virus, “Dr. Jefferson believes that the virus may be transmitted through the sewage system or shared toilet facilities, not just through droplets expelled by talking, coughing, and sneezing,” The Telegraph reported.
“There is quite a lot of evidence that huge amounts of the virus in sewage [are] all over the place, and an increasing amount of evidence there is fecal transmission,” he told The Telegraph. “There is a high concentration where sewage is four degrees [Celsius], which is the ideal temperature for it to be stabled and presumably activated. And meatpacking plants are often at four degrees. These meat packing clusters and isolated outbreaks don’t fit with respiratory theory, they fit with people who haven’t washed their hands properly.”
“It’s implausible that there was a hidden pandemic before it actually started,” he told Euronews. “If that’s the assertion, that’s a pretty wild accusation actually, because it flies in the face of all we know about how this epidemic has evolved.”
Lundgren also questioned the findings from Spain, Italy, and Brazil. “They haven’t found the same virus,” he said, only “molecular evidence that there is shared genetic material.”
The Spanish, Italian, and Brazilian studies have not been peer reviewed, and some experts have suggested alternative explanations for the positive test results, including “the potential for a false positive due to the virus’ similarities with other respiratory infections,” Reuters reported.
“When it’s just one result, you always want more data, more studies, more samples to confirm it and rule out a laboratory error or a methodological problem,” Joan Ramon Villalbi, MD, PhD, MPH, of the Spanish Society for Public Health and Sanitary Administration told Reuters. “But it’s definitely interesting, it’s suggestive,” he added.
Writing in The Conversation about the Barcelona study, Claire Crossan, PhD, Research Fellow, Virology, Glasgow Caledonian University, raised the possibility of lab contamination and questioned why there were no reported spikes in respiratory disease cases after the sample was taken.
“If this result is a true positive it suggests the virus was present in the population at a high enough incidence to be detected in an 800ml sample of sewage, but then not present at a high enough incidence to be detected for nine months, when no control measures were in place,” she wrote.
Though nothing definitive may come from these studies, they do indicate that there’s still much to learn about the origin of the SARS-CoV-2 coronavirus. Clinical laboratory leaders would be wise to keep an eye on these developments.
Though lenders and landlords may be willing to renegotiate terms, communication is key, the lawyers suggest
COVID-19 has vastly increased demand for clinical laboratory testing. But at many labs, the pandemic has caused much damage to the bottom line. Due to numerous factors—including reductions in elective procedures and increased operating costs—many independent lab companies have seen a 30% to 60% cut in revenue, says attorney Richard S. Cooper, JD, of McDonald Hopkins, a law firm that represents more than 350 medical laboratories across the US.
“Some of that was offset where clinical laboratory companies took on COVID testing. But in our experience, it was a partial offset at best,” he said in an exclusive interview with Dark Daily. Cooper is co-chair of the firm’s National Healthcare Practice Group.
To address these challenges, the firm has advised lab companies to take a hard look at their:
operations,
market conditions,
supplier relationships,
lender agreements, and
other elements of their businesses.
Lab executives, he says, should consider steps to reduce expenses or increase revenues, such as increasing prices if conditions permit. In extreme cases, medical laboratories may have to consider:
Chapter 11 bankruptcy,
Consensual out-of-court restructuring, or
Buyouts.
“I think lenders have been willing to work with borrowers, but I don’t think this has been a ‘get out of jail free’ card,” Richard S. Cooper, JD (above), co-chair of the National Healthcare Practice Group at McDonald Hopkins, told Dark Daily. “Lenders are going to look at borrowers that were struggling before the whole COVID-19 situation with a more critical eye. Lenders seem to be more willing to work with borrowers that were doing well, but then were hit with a temporary hiccup.” (Photo copyright: McDonald Hopkins.)
Cooper, and colleague Jason M. Smith, JD, elaborated on these points during the interview. Smith is chair of the Commercial Finance Group. “The vast majority of my work is representing either lenders or borrowers in credit relationships,” Smith explained.
Dealing with Lenders
For many lab companies facing financial distress, the most important action, the lawyers suggest, may be to review loan or credit agreements and get a better understanding of the lab’s obligations. Then, the lab can approach lenders for potential relief, such as deferred payments or temporary adjustments to reporting requirements.
Either way, “communication is key,” Smith said, adding that labs should first “come up with projections and cashflow analyses and figure out which of those requirements they are not going to be able to meet.”
Then, Smith added, labs should reach out proactively. “Lenders generally don’t like surprises,” he said. “They’re going to be a lot more willing to work with you when they find out about any issues directly from you, as opposed to after receiving financial statements and discovering the issues for themselves.”
Ultimately, clinical lab companies may be able to negotiate better terms, not only with financial institutions, but also with landlords, Cooper said. For example, labs may ask for rent abatement or payment deferrals. These steps “may reduce or eliminate the need to cut back on staff,” Cooper said, “which may be less disruptive of operations.”
When dealing with lenders, Cooper advises against a “Let’s throw everything at the wall and see what sticks” approach. Instead, labs should try “concrete, smaller lists of things that are really important. That’s the best way to come up with a reasonable ask for your lenders and have them take you seriously.”
When to Call Your Lawyer
Cooper says lawyers can play two different roles in these negotiations. “It’s important that lab executives discuss with their lawyers any potential violations of lease and lending documents, what the obligations are, and what the potential legal impact may be.” He added, “Labs should engage and discuss with a lawyer who’s experienced in those areas to understand how lenders and financial institutions might be willing to accommodate the lab’s financial situation by suspending or temporarily modifying the terms of those documents.”
Jason M. Smith, JD (above), chair of the Commercial Finance Group at McDonald Hopkins, told Dark Daily, “Clinical laboratory companies could approach their lender and/or landlord directly. You don’t necessarily need a lawyer to do that. On the other hand, a lot of clients prefer that their lawyer at least participate in any dialogue with the landlord and lender. But it’s not absolutely necessary. So, the lawyer can be an information resource or an active participant in negotiating.” (Photo copyright: McDonald Hopkins.)
The Bankruptcy Option
Clinical laboratory companies that are in serious financial trouble may have to consider drastic measures, such as bankruptcy. In a Chapter 11 bankruptcy, Cooper explains, you can continue to operate under supervision of the court while restructuring the business and renegotiating terms with lenders. But “there’s always a stigma attached to any kind of restructuring filing,” he said. “It’s public and it can raise questions among your suppliers and customers as to whether you’re sustainable. So, it would be more of a last measure.”
A more preferable course, he says, may be to negotiate a consensual out-of-court workout in which creditors agree to extend repayment terms or reduce debt.
A Good Time for Buyouts?
Another option for distressed lab companies may be buyouts. “We are starting to see a pickup in [merger and acquisition] activity,” Cooper says. “Some of it is normal activity not necessarily driven by financial distress. There’s a company that’s attractive in the marketplace and buyers are interested in that laboratory.”
In other situations, he noted, clinical laboratories might not feel compelled to sell, but “they want to become part of a larger platform with better capital resources to help them withstand the COVID-19 scenario and future market-altering events.”
Cooper continued, “there are other labs that basically say, ‘We’re not going to make it on our own. We need to find a buyer. We need to find capital.’ And then, of course, there are buyers that see market opportunities in labs which are available for acquisition that otherwise might not have been, and perhaps on more favorable terms.”
Some labs, he says, may wait for their revenues to recover, so they can “go to market in a stronger position.” But, “there clearly will be some labs out there that will be available, and available at a lower price than they would have been pre-COVID.”
Regardless of which path a financially-distressed clinical lab company chooses to take as a way to resolve the situation, it is best to take the initiative to consult with experienced attorneys, CPAs, and other advisors while there is still time to negotiate different solutions with lenders, landlords, mortgage companies, and others.
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.
