Available funds and disease prevalence affect whether pooled testing is feasible and desirable, notes University of Kansas Health System microbiology laboratory director
Pooled testing for the SARS-CoV-2 coronavirus has its supporters and its critics. There is no one-size-fits-all when it comes to pooling multiple patients’ biological samples into a single COVID-19 test in the hopes that the result will be all negative. Several factors must be in place for COVID-19 pooled testing to be viable at individual clinical laboratories. The experience of medical labs that considered doing pooled testing are informative.
For example, when Rachael Liesman, PhD, Director of Microbiology in Pathology and Laboratory Medicine at the University of Kansas Health System in Kansas City, researched developing a plan for pooled testing of COVID-19 patients for her health system, she found the strategy less than ideal for two reasons:
First was the rate of infection in the population being tested. If the rate was too high, pooled testing produced too many positive results, making the process impractical.
Second was the need for expensive automated equipment in the microbiology laboratory, the funding to buy that equipment, and the room to accommodate it.
Last summer, as Liesman and her microbiology lab staff were evaluating pooled testing, she spoke with Dark Daily’s sister publication The Dark Report. “We were trying to decide whether pooled testing really would save us anything,” she said in the exclusive interview. “We were looking at the barriers and trying to understand what we’d gain and what we’d lose.”
Deciding Against Pooled Testing at University of Kansas Health System
After careful consideration, the lab staff stopped considering pooled testing due to increased prevalence in the community, Liesman said in December. “Our positivity rate is double what we were seeing in the summer,” she noted.
“Of course, the biggest challenge with pooling specimens is you have to have a patient population that has a low enough virus prevalence to make it worth your time,” she noted. “For us, there may be some patient populations that have a low enough level of prevalence, but not enough to make pooling feasible.”
University of Kansas Health System’s microbiology laboratory has been running 800 to 1,000 COVID-19 molecular tests 24 hours a day, seven days a week, although the lab runs fewer tests on the weekends. On Jan. 8, the number of new coronavirus cases in Kansas was at 1,780 per million, according to the COVID Tracking Project (CTP). That was about the highest rate since the pandemic began early in the year.
“Pooling makes a lot of sense for massive high-volume reference labs. I don’t have the capacity to run 6,000 specimens a day through my lab,” noted Rachael Liesman, PhD (above), Director of Microbiology in Pathology and Laboratory Medicine at the University of Kansas Health System, in an exclusive interview with The Dark Report. Not all clinical laboratories can or should consider pooled testing, which Dark Daily noted in previous e-briefings. (Photo copyright: Twitter.)
“One of the challenges in any lab is when you get specimens arriving in volume of say 100 or 200 specimens every few hours,” Liesman explained. “When that happens, you have to determine rapidly which of those specimens you would want to pool and which of them you wouldn’t pool. Or, if you had the right circumstances, you could pool all of them.
“You might have asymptomatic patients in one group and symptomatic patients in another group. So, then you could put all samples from one group into a pool. But if you’re not set up that way, just figuring that part out could be really time consuming,” she noted.
“Another challenge,” Liesman added, “is if your laboratory doesn’t have liquid handlers, which are the instruments that do the pooling for you.”
Manual versus Automated Pooling
In a clinical laboratory without liquid handlers, the task of pooling is not automated and instead requires staff to do the work manually—one specimen and one pool at a time.
Without the right equipment, Liesman noted, somebody in the lab must physically take five tubes and combine them in into one tube. And that one person has to ensure the test tube of pooled specimens is appropriately stickered. Then, once that is completed, the information must be input into the laboratory information system (LIS).
“We have a liquid handler because we purchased one from Hamilton specifically for COVID testing. But getting all that information into the computer system can take a lot of time,” she said. “A lot of labs don’t have access to this type of instrumentation, which means the process becomes very hands-on.
“We already see repetitive-use injuries, and if many of your staff are spending their eight-hour shifts doing pipetting motions, then they’re at greater risk for repetitive-use injury,” she added.
In addition, having humans doing repetitive motions in a clinical laboratory increases the risk of specimen-handling errors such as tubes being mislabeled or misplaced. “Those mistakes are very hard to find,” Liesman noted. “For us, we’ve been asking if we have the resources to do pooling successfully. And, if we put all these resources into it, what do we gain? That’s the big question for us.”
For a clinical laboratory to successfully initiate and maintain an effective program for pooled testing of the SARS-CoV-2 coronavirus, it must have specific equipment available to reduce manual touches of the specimens and automate as many work processes as possible. The lab’s manager must also consider the staffing required to handle pooled testing. Even then, if disease prevalence climbs above a certain level, pooled testing will not be a viable solution.
These are the reasons why many medical laboratories have considered a pooled testing arrangement but decided it would not be appropriate for their organization. Meanwhile, at other clinical labs pooled SARS-CoV-2 testing has been a major success, partly because it enables the labs to test many more patients using the same quantity of test kits and related supplies.
The No Surprises Act, passed as part of the COVID-19 relief package, ensures patients do not receive surprise bills after out-of-network care, including hospital-based physicians such as pathologists
Consumer demand for price transparency in healthcare has been gaining support in Congress after several high-profile cases involving surprise medical billing received widespread reporting. Dark Daily covered many of these cases over the years.
Now, after initial opposition and months of legislative wrangling, organizations representing medical laboratories and clinical pathologists have expressed support for new federal legislation that aims to protect patients from surprise medical bills, including for clinical pathology and anatomic pathology services.
The new law Congress passed is known as the No Surprises Act (H.R.3630) and is part of the $900 billion COVID relief and government funding package signed by President Trump on December 27.
The law addresses the practice of “balance billing,” in which patients receive surprise bills for out-of-network medical services even when they use in-network providers. An ASCP policy statement noted that “a patient (consumer) may receive a bill for an episode of care or service they believed to be in-network and therefore covered by their insurance, but was in fact out-of-network.” This, according to the ASCP, “occurs most often in emergency situations, but specialties like pathology, radiology, and anesthesiology are affected as well.”
Most portions of the No Surprises Act take effect on January 1, 2022. The law prohibits balance billing for emergency care, air ambulance transport, or, in most cases, non-emergency care from in-network providers. Instead, if a patient unknowingly receives services from an out-of-network provider, they are liable only for co-pays and deductibles they would have paid for in-network care.
New Law Bars Pathologists from Balance Billing without Advance Patient Consent
The law permits balance billing under some circumstances, but only if the patient gives advance consent. And some specialties, including pathologists, are barred entirely from balance billing.
The law also establishes a process for determining how healthcare providers are reimbursed when a patient receives out-of-network care. The specifics of that process proved to be a major sticking point for providers. In states that have their own surprise-billing protections, payment will generally be determined by state law. Otherwise, payers and providers have 30 days to negotiate payment. If they can’t agree, payment is determined by an arbiter as part of an independent dispute resolution (IDR) process.
Early Proposal Drew Opposition
An early proposal to prohibit surprise billing drew opposition from a wide range of medical societies, including the ASCP, CAP, and the American Medical Association (AMA).
All were signatories to a July 29, 2020, letter sent to leaders of the US Senate and House of Representatives urging them to hold off from enacting surprise billing protections as part of COVID relief legislation. Though the groups agreed in principle with the need to protect patients from surprise billing, they contended that the proposed legislation leaned too heavily in favor of insurers, an ASCP news release noted.
“Legislative proposals that would dictate a set payment rate for unanticipated out-of-network care are neither market-based nor equitable, and do not account for the myriad inputs that factor into payment negotiations between insurers and providers,” the letter stated. “These proposals will only incentivize insurers to further narrow their provider networks and would also result in a massive financial windfall for insurers. As such, we oppose the setting of a payment rate in statute and are particularly concerned by proposals that would undermine hospitals and front-line caregivers during the COVID-19 pandemic.”
On December 11, leaders of key House and Senate committees announced agreement on a bipartisan draft of the bill that appeared to address these concerns, including establishment of the arbitration process for resolving payment disputes.
However, in a letter sent to the committee chairs and ranking members, the AHA asked for changes in the dispute-resolution provisions, including a prohibition on considering Medicare or Medicaid rates during arbitration. “We are concerned that the IDR process may be skewed if the arbiter is able to consider public payer reimbursement rates, which are well known to be below the cost of providing care,” the association stated. However, legislators agreed to the change after last-minute negotiations.
“The AHA is pleased that Congress rejected approaches that would impose arbitrary rates on providers, which could have significant consequences far beyond the scope of surprise medical bills and impact access to hospital care,” AHA President and CEO Rick Pollack (above) said in a statement. “We also applaud Congress for rejecting attempts to base rates on public payers.” (Photo copyright: American Hospital Association.)
Dispute Resolution for Pathologists
The CAP also expressed support for the final bill. In a statement, CAP noted that “As the legislation evolved during the 116th Congress, CAP members met with their federal lawmakers to discuss the CAP’s policy priorities.
“Through the CAP’s engagement and collaboration with other physician associations, the legislation improved drastically,” the CAP stated. “Specifically, the CAP lobbied Congress to hold patients harmless, establish a fair reimbursement formula for services provided, deny insurers the ability to dictate payment, create an independent dispute resolution (IDR) process that pathologists can participate in, and require network adequacy standards for health insurers.”
As laboratory testing was identified by thousands of respondents to the University of Chicago survey as the top surprise bill, it is likely that billing and transparency in charges for clinical pathologist and anatomic pathologist will continue to be scrutinized by law makers and healthcare associations.
With improved genetic sequencing comes larger human genome databases that could lead to new diagnostic and therapeutic biomarkers for clinical laboratories
As the COVID-19 pandemic grabbed headlines, the human genome database at the US Department of Veterans Affairs Million Veterans Program (MVP) quietly grew. Now, this wealth of genomic information—as well as data from other large-scale genomic and genetic collections—is expected to produce new biomarkers for clinical laboratory diagnostics and testing.
In December, cancer genomics company Personalis, Inc. (NASDAQ:PSNL) of Menlo Park, Calif., achieved a milestone and delivered its 100,000th whole human genome sequence to the MVP, according to a news release, which also states that Personalis is the sole sequencing provider to the MVP.
The VA’s MVP program, which started in 2011, has 850,000 enrolled veterans and is expected to eventually involve two million people. The VA’s aim is to explore the role genes, lifestyle, and military experience play in health and human illness, notes the VA’s MVP website.
Health conditions affecting veterans the MVP is researching include:
The VA has contracted with Personalis through September 2021, and has invested $175 million, Clinical OMICS reported. Personalis has earned approximately $14 million from the VA. That’s about 76% of the company’s revenue, according to 2nd quarter data, Clinical OMICS noted.
“The VA MVP is the largest whole genome sequencing project in the United States, and this is a significant milestone for both the program and for Personalis,” said John West (above with wife Judy), Founder and CEO of Personalis, in the news release. “Population-scale sequencing projects of this nature represent a cornerstone in our effort to accelerate the advancement of precision medicine across a wide range of disease areas,” he added. (Photo copyright: MIT Technology Review.)
Database of Veterans’ Genomes Used in Current Research
What has the VA gained from their investment so far? An MVP fact sheet states researchers are tapping MVP data for these and other veteran health-related studies:
Differentiating between prostate cancer tumors that require treatment and others that are slow-growing and not life-threatening.
How genetics drives obesity, diabetes, and heart disease.
How data in DNA translates into actual physiological changes within the body.
Gene variations and patients’ response to Warfarin.
NIH Research Program Studies Effects of Genetics on Health
Another research program, the National Institutes of Health’s All of Us study, recently began returning results to its participants who provided blood, urine, and/or saliva samples. The NIH aims to aid research into health outcomes influenced by genetics, environment, and lifestyle, explained a news release. The program, launched in 2018, has biological samples from more than 270,000 people with a goal of one million participants.
“We’re changing the paradigm for research. Participants are our most important partners in this effort, and we know many of them are eager to get their genetic results and learn about the science they’re making possible,” said Josh Denny, MD, CEO of the NIH’s All of Us research program in the news release. Denny, a physician scientist, was Professor of Biomedical Informatics and Medicine, Director of the Center for Precision Medicine and Vice President for Personalized Medicine at Vanderbilt University Medical Center prior to joining the NIH. (Photo copyright: National Institutes of Health.)
Inclusive Data Could Aid Precision Medicine
The news release notes that more than 80% of biological samples in the All of Us database come from people in communities that have been under-represented in biomedical research.
“We need programs like All of Us to build diverse datasets so that research findings ultimately benefit everyone,” said Brad Ozenberger, PhD, All of Us Genomics Program Director, in the news release.
Precision medicine designed for specific healthcare populations is a goal of the All of Us program.
“[All of Us is] beneficial to all Americans, but actually beneficial to the African American race because a lot of research and a lot of medicines that we are taking advantage of today, [African Americans] were not part of the research,” Chris Crawford, All of US Research Study Navigator, told the Birmingham Times. “As [the All of Us study] goes forward and we get a big diverse group of people, it will help as far as making medicine and treatment that will be more precise for us,” he added.
Large Databases Could Advance Care
Genome sequencing technology continues to improve. It is faster, less complicated, and cheaper to sequence a whole human genome than ever before. And the resulting sequence is more accurate.
Thus, as human genome sequencing databases grow, researchers are deriving useful scientific insights from the data. This is relevant for clinical laboratories because the new insights from studying bigger databases of genomic information will produce new diagnostic and therapeutic biomarkers that can be the basis for new clinical laboratory tests as well as useful diagnostic assays for anatomic pathologists.
The remarkably low number of influenza diagnoses makes it possible for clinical laboratories to stay focused on COVID-19
One positive note for clinical laboratories this winter is the fact that the number of biological samples being submitted for influenza (flu) testing have dropped significantly. This has given medical laboratories more resources for processing COVID-19 tests.
According to a feature published in Nature, the number of samples being submitted to medical laboratories for flu testing has dropped by 61%. More surprisingly, the number of positives has dropped by 98%. The combined flu/COVID-19 “twindemic” that some medical experts feared could crush our healthcare system has not materialized—yet, the Washington Examiner reported.
“In any given winter, hospitals are taxed by the flu,” Brian Garibaldi, MD, a pulmonologist and critical care specialist and Medical Director of the Johns Hopkins Biocontainment Unit told the Washington Examiner. “There’s always a concern that our emergency departments will be overwhelmed, and ICU capacity will be strained [due to the concurrence of flu and COVID-19 outbreaks], particularly with people who have coexisting conditions that then get influenza.”
The 2019-2020 flu season ended earlier than usual, likely because of precautions put in place in the spring to combat the coronavirus pandemic. Most years, the seasonal flu in the US peaks in February and trails off by May, Nature reported in “How Coronavirus Lockdowns Stopped Flu in Its Tracks.”
“Seasonal flu cases in the northern hemisphere usually peak in February and tail off by the end of May,” Nature wrote. “This year, unusually, lab-confirmed cases of influenza dropped precipitously in early April, a few weeks after the coronavirus pandemic was declared on 11 March. The data comes from tests of more than 150,000 samples from national influenza laboratories in 71 countries that report data to FluNet, a global surveillance system.”
Government Leaders and Health Experts Remain Concerned
Despite that encouraging data point, public health experts and political leaders were still concerned. In September, Arizona Governor Doug Ducey said, “The overlap of COVID-19 and flu season presents a perfect storm, and we aren’t taking any chances. We are approaching this fall with a proactive mindset and plan of action to limit the impact of the flu and preserve hospital resources,” the Washington Examiner reported.
The caution was certainly warranted. A normal flu season strains resources, but a severe flu season coupled with a global pandemic could have been disastrous. Luckily, Ducey’s “perfect storm” did not materialize.
Data from the World Health Organization’s FluNet Global Influenza Surveillance and Response System was used by Nature to develop the graphic above. It illustrates how the number of positive Influenza specimens in 2019-2020 declined compared to the previous two years. Some experts believe this is due to protocols implemented to combat the COVID-19 coronavirus by hospitals and clinical laboratories. (Graphic copyright: Nature.)
Why Is There Less Influenza?
So, why is there less flu and other respiratory infections?
Epidemiologist Lisa Lockerd Maragakis, MD, MPH, Associate Professor of Medicine and Senior Director of Infection Prevention at Johns Hopkins Health System, told U.S. News, widespread business and school closures provide fewer opportunities for influenza to spread. “We commonly see flu spread in communities, schools, businesses and through travel each year, so those changes are likely keeping the flu away.”
However, this may have a negative effect as well. Eili Klein, PhD, Associate Professor of Emergency Medicine at Johns Hopkins School of Medicine, warns that “Because of the current restrictions and precautions everyone is taking this season, far fewer people will be infected or exposed to the flu virus, and therefore won’t become immune to certain strains of the virus. So, the number of people who may have more severe infections next year is likely to be greater because immunity will be lower,” the Washington Examiner reported.
Other Viral Infections Also in Decline Due to COVID-19 Precautions, Vaccines
Masking, frequent handwashing, and social distancing certainly played a role in reducing the number of cases of flu reported this year. But influenza is not the only disease that saw reductions. “In Hong Kong, compared with previous years, the number of chickenpox cases dropped by about half to three-quarters,” Nature reported. “In April, cases of measles and rubella were their lowest, globally, since at least 2016, according to data available so far.”
Early in the COVID-19 pandemic, some public health officials were concerned that the decline in influenza cases was actually related to a lack of testing. “However, renewed efforts by public health officials and clinicians to test samples for influenza resulted in adequate numbers tested and detection of little to no influenza virus,” the Centers for Disease Control and Prevention (CDC) reported.
Another factor in the lower numbers of flu cases could be due to the fact that more people have gotten vaccinated this year. More than 188 million flu vaccines were distributed in 2020, an increase compared to the 169 million given in 2019.
“Flu vaccination in the community started earlier this year, as recommended by the CDC, and our community physicians report that vaccine uptake has been higher than usual,” Marie-LouiseLandry, MD, Clinical Virologist, Professor of Laboratory Medicine and of Medicine (Infectious Diseases), and Director of the Clinical Virology Laboratory at Yale School of Medicine, told Healthline.
It may also be that influenza diagnoses are fewer because people are not seeking treatment. Hospitals at or beyond capacity due to the pandemic, or fear of contracting COVID-19, may have motivated people with flu-like symptoms to stay home rather than seek treatment. However, most healthcare experts agree that public health measures to fight COVID-19 are likely the larger reason there is less flu.
“Public health measures such as movement restrictions, social distancing, and increased personal hygiene likely had an effect on decreasing influenza and other respiratory virus transmissions,” the World Health Organization (WHO) told Nature.
What About the Next Flu Season?
Experts are more conflicted regarding what all of this means for coming flu seasons. Some experts think that because there’s less flu this year, there will be less immunity next year, and severe illness will result. Others are more optimistic and hope that some strains of flu will disappear, which could mean less flu in the immediate future. It’s not a simple prediction to make.
Even if the low flu numbers this year mean some strains do not survive, it is unlikely that will remain the case. “I am sure that flu will come back with a vengeance at some stage in the future,” Robert Ware, PhD, a biostatistician, clinical epidemiologist, and Professor of Biostatistics with Griffith University in Queensland, Australia, told Nature.
Thus, clinical laboratories should remain vigilant for future influenza outbreaks. Hopefully by then the COVID-19 pandemic will have peaked and labs will be able to reallocate testing resources appropriately.
The latest McKinsey report addresses when the COVID-19 pandemic is “most likely” to end and what needs to happen to get there
Clinical laboratory leaders, pathologists, and diagnostics professionals everywhere want to know when the SARS-CoV-2 coronavirus will burn itself out. When can we expect to return to normal? Since there is no such thing as a crystal ball, it might be helpful to review the latest report from international management consulting firm McKinsey and Company, titled, appropriately, “When Will the COVID-19 Pandemic End?”
It’s a good question, and McKinsey is not certain of the answer. Barring other factors, McKinsey predicts “Transition toward normalcy in the United States remains most likely in the second quarter of 2021 and herd immunity in the third and fourth quarters, but the emergence of new strains and a slow start to vaccine rollout raise real risks to both timelines.” The report also states, “the emergence of more-infectious variants of SARS-CoV-2 increases the risk that this milestone will not be achieved until later.
“More-infectious viruses,” McKinsey continued, “require that a higher percentage of people be simultaneously immune to reach herd immunity. While a more infectious variant likely means more people are acquiring natural immunity through infection (despite ongoing efforts to minimize new cases), the net impact of more-infectious strains is likely to be that a higher portion of the population needs to be vaccinated, which may take more time.”
Challenges That May Slow Herd Immunity to COVID-19
“It is now harder to imagine the United States or United Kingdom transitioning to normalcy before second quarter 2021 or reaching herd immunity before third quarter 2021,” McKinsey added. “Herd immunity to a pathogen is achieved when a sufficient portion of a population is simultaneously immune to prevent sustained transmission.”
But problems in [COVID-19] vaccine distribution, supply shortages, and intermittent participation by the population could push the pandemic endpoint to 2022, cautioned McKinsey.
“We believe herd immunity in the United States is still most likely in third or fourth quarter 2021, but that the chance of delay until first quarter 2022 or beyond has increased,” the report states, “Even later herd immunity remains possible if other challenges arise, especially vaccine safety concerns or ambivalence to vaccination following a transition toward normalcy.”
Other factors that went into the firm’s “most likely” set of possible timelines include:
“Unexpected safety issues emerging with early vaccines,
“Significant manufacturing or supply-chain delays,
“Continued slow adoption,
“Further mutation [of the virus],
“A shorter-than-anticipated duration of vaccine-conferred immunity.”
The graph above, taken from the McKinsey and Co. report, illustrates how “the probability of reaching COVID-19 herd immunity in the United States is highest in the third or fourth quarter, but could shift.” (Graphic copyright: McKinsey and Company.)
A ‘Transition Toward Normalcy’
In its report, McKinsey notes that “During this transition, controlling the spread of SARS-CoV-2 will still require public-health measures (such as continued COVID-19 testing and mask use in many settings), but mortality will fall significantly, allowing greater normalization of business and social activities.”
In apparent agreement, according to data from the COVID Tracking Project, as of Jan. 27, 2021, 107,444 people were hospitalized in the US with COVID-19, as compared to 130,000 hospital cases on Jan. 13, 2021. Numbers of new cases appear to be dropping, however, McKinsey predicts that “COVID-19 will not disappear during this transition but will become a more normal part of the baseline disease burden in society (like flu, for example), rather than a special threat requiring exceptional societal response.”
It may help that more people are taking one of the vaccines. A recent survey conducted by London-based research and analytics firm YouGov, found that people worldwide are becoming more willing to take the COVID-19 vaccine. For example, in the UK, 80% of those surveyed gave a thumbs-up to getting vaccinated, compared to 61% in November. In the US, however, still only about 45% said they will get the vaccine, up slightly from 42% who said so in July, YouGov reported.
However, McKinsey points out that “vaccine rollout has not yet proceeded far enough to protect much of the population.”
How Should Medical Laboratories and Other Healthcare Providers Proceed?
In “No One Said it Would Be Easy,” Jan. 22, 2021, Becker’s Hospital Review, Michael Dowling, President and CEO of Northwell Health, wrote, “We will be living in a world preoccupied by COVID-19 and vaccination for many months to come … And the stark reality is that the vaccination rollout will continue well into the summer, if not longer, while at the same time we continue to care for hundreds of thousands of Americans sickened by the virus. Despite the challenges we face now and in the coming months in treating the disease and vaccinating a US population of 330 million, none of us should doubt that we will prevail.”
“To achieve that,” McKinsey notes, “we will need to see significant progress on the epidemiological end point … Favorable findings on natural and cross-immunity would help accelerate timelines.
“Five additional criteria will also contribute to the transition to a form of normalcy—the more of these that are achieved, the faster the milestone is likely to be reached:
“Continued improvement by governments in the application of public-health interventions (such as test and trace) that don’t significantly limit economic and social activities.
“Compliance with public-health measures until we achieve herd immunity.
“Accurate, widely available, rapid testing that effectively enables specific activities.
“Continued advancements in therapeutics (including pre- and post-exposure prophylactics) for and clinical management of COVID-19, leading to lower infection-fatality ratios—substantial progress has already been made through a combination of effective drugs, such as Dexamethasone and Remdesivir, and changes in clinical management.
“Public confidence that there aren’t significant long-term health consequences for those who recover from COVID-19.”
Finally, McKinsey notes that “Both the epidemiological and normalcy ends to the COVID-19 pandemic are important. The transition to the next normal will mark an important social and economic milestone, and herd immunity will be a more definitive end to the pandemic. In the United States, while the transition to normal might be accomplished sooner, the epidemiological end point looks most likely to be reached in the second half of 2021.”
It is not clear when clinical laboratories and pathologists will know for certain when the pandemic’s end point has been reached. Predictions coming from sources such as McKinsey’s latest report may be as close as we get to a crystal ball view of the pandemic’s future.
