Understanding why some people display no symptoms during a COVID-19 infection could lead to new precision medicine genetic tests medical labs could use to identify people with the mutated gene
New research from the University of California San Francisco (UCSF) may explain why some people could get COVID-19 but never test positive on a clinical laboratory test or develop symptoms despite exposure to the SARS-CoV-2 coronavirus.
According to the UCSF study, variations in a specific gene in a system of genes responsible for regulating the human immune system appears to be the factor in why about 10% of those who become infected with the virus are asymptomatic.
These scientific insights did not receive widespread news coverage but will be of interest to clinical laboratory managers and pathologists who oversee SARS-CoV-2 testing in their labs.
“Some people just don’t have symptoms at all,” Jill Hollenbach, PhD (above), Professor of Neurology atUCSF’s Weill Institute for Neurosciences and lead researcher in the study, told NBC News. “There’s something happening at a really fundamental level in the immune response that is helping those people to just completely wipe out this infection.” Identifying a genetic reason why some people are asymptomatic could lead to new precision medicine clinical laboratory diagnostics for COVID-19. (Photo copyright: Elena Zhukova /University of California San Francisco.)
Fortunate Gene Mutation
According to the Centers for Disease Control and Prevention’s (CDC) COVID Data Tracker, as of April 5, 2023, a total of 104,242,889 COVID-19 cases have been reported in the United States. However, according to a CDC Morbidity and Mortality Weekly Report (MMWR), “Traditional methods of disease surveillance do not capture all COVID-19 cases because some are asymptomatic, not diagnosed, or not reported; therefore, [knowing the true] proportion of the population with SARS-CoV-2 antibodies (i.e., seroprevalence) can improve understanding of population-level incidence of COVID-19.”
She also participates in the COVID-19 HLA and Immunogenetics Consortium, a group of academic researchers, clinical laboratory directors, journal editors, and others who examine the role of HLA variations in determining COVID-19 risk.
Hollenbach’s research identified an HLA variant—known as HLA-B*15:01—that causes the human immune system to react quickly to SARS-CoV-2 and “basically nuke the infection before you even start to have symptoms,” she told NPR.
“It’s definitely luck,” she added. “But, you know, this [gene] mutation is quite common. We estimate that maybe one in 10 people have it. And in people who are asymptomatic, that rises to one in five.”
“HLA variants are among the strongest reported associations with viral infections,” the UCSF study notes. So, the researchers theorized that HLA variations play a role in asymptomatic SARS-CoV-2 infections as well.
To conduct their study, shortly after the SARS-CoV-2 outbreak in 2020, the researchers recruited approximately 30,000 volunteer bone marrow donors from the National Marrow Donor Program to respond to periodic questions via a smartphone app or website. Because HLA variations can determine appropriate matches between donors and recipients, the database includes information about their HLA types.
Each week, respondents were asked to report if they had been tested for SARS-CoV-2. Each day, they were asked to report whether they had symptoms associated with COVID-19. “We were pretty stringent in our definition of asymptomatic,” Hollenbach told NBC News. “[The respondents couldn’t] even have a scratchy throat.”
The researchers eventually identified a cohort of 1,428 people who had tested positive for SARS-CoV-2 between February 2020 and April 30, 2021, before vaccines were widely available. Among these individuals, 136 reported no symptoms for two weeks before or two weeks after a positive test.
“Overall, one in five individuals (20%) who remained asymptomatic after infection carried HLA-B*15:01, compared to 9% among patients reporting symptoms,” the researchers wrote in their medRxiv preprint. Study participants with two copies of the gene were more than eight times more likely to be asymptomatic.
The UCSF researchers also looked at four other HLA variants and found none to be “significantly associated” with lack of symptoms. They confirmed their findings by reproducing the HLA-B association in two additional independent cohorts, one from an earlier study in the UK and the other consisting of San Francisco-area residents.
Individuals in the latter group had either tested positive for SARS-CoV-2 or reported COVID symptoms, and their DNA was analyzed to determine their HLA types.
Pre-existing T-Cell Immunity May Reduce Severity of COVID-19 Infection
The UCSF researchers also attempted to determine how HLA-B*15:01 plays a role in knocking out SARS-CoV-2 infections. They noted previous research that indicated previous exposure to seasonal coronaviruses, such as common cold viruses, could limit the severity of COVID-19. The scientists hypothesized that pre-existing T-cell immunity in HLA-B carriers may be the key.
The COVID-19 HLA and Immunogenetics Consortium website describes how HLA and T-cells work together to ward off disease. HLA “proteins are found on the surface of all cells except red-blood cells.” They’re “like windows into the inner workings of a cell,” and T-cells use the molecules to determine the presence of foreign proteins that are likely signs of infection. “Activated T-cells can kill infected cells, or activate B-cells, which produce antibodies in response to an infection,” the website explains.
Hollenbach’s research team analyzed T-cells from pre-pandemic individuals and observed that in more than half of HLA-B carriers, the T-cells were reactive to a SARS-CoV-2 peptide. The scientists corroborated the hypothesis by examining crystal structures of the HLA-B*15:01 molecule in the presence of coronavirus spike peptides from SARS-CoV-2 and two other human coronaviruses: OC43-CoV and HKU1-CoV.
“Altogether, our results strongly support the hypothesis that HLA-B*15:01 mediates asymptomatic COVID-19 disease via pre-existing T-cell immunity due to previous exposure to HKU1-CoV and OC43-CoV,” the researchers wrote.
Can Genes Prevent COVID-19 Infections?
Meanwhile, researchers at The Rockefeller University in New York City are attempting to go further and see if there are mutations that prevent people from getting infected in the first place. NPR reported that they were seeking participants for a study seeking to identify so-called “superdodger” genes.
Study participants identified as possibly having superdodger genes receive a kit designed to collect saliva samples, after which the researchers sequence the respondents’ genomes. “We hope that in a group of 2,000 to 4,000 people, some people will have genetic mutations that tell us why they’re resistant to infection,” Casanova told NPR.
All this genetic research is in very early stages. But results are promising and may lead to new precision medicine clinical laboratory tests for identifying people who are predisposed to having an asymptomatic response to COVID-19 infection. That in turn could help scientists learn how to moderate or even eliminate symptoms in those unfortunate people who suffer the typical symptoms of the disease.
Hospital-at-home programs like that of Atrium Health are a trend that may create new opportunities for local clinical laboratories to support physicians treating patients in the comfort of their own homes
Here is a deal that shows the hospital-at-home (HaH) movement is gaining momentum, a trend that clinical laboratories need to recognize for the opportunities it represents. Best Buy Health is partnering with 40-hospital Atrium Health in an HaH program that the healthcare system plans to scale nationally.
This newly-announced collaboration means that Charlotte, North Carolina-based Atrium Health—as partner—may include the hospitals and providers that are part of the 26-hospital Advocate Aurora Health system (now known as Advocate Health), a non-profit healthcare system that Atrium merged with in December of 2022. Providers and hospitals from North/South Carolina, Georgia, Wisconsin, Illinois, Indiana, and Ohio all could be participating in the new HaH venture.
This latest partnership between a retail giant and healthcare network demonstrates how innovation is working its way into the US healthcare system via companies not traditionally involved in direct patient care. These two organizations see an opportunity to combine their strengths to “enhance the patient experience of receiving hospital-level care at home,” according to a Best Buy news release.
“This is the coming together of technology and empathy,” said Rasu Shrestha, MD (above), Executive Vice President and Chief Innovation and Commercialization Officer at Advocate Health, in a press release. “We’re able to leverage the power of social workers, paramedics, nurses and physicians, but also technology to take care of the patients in their homes. We can bring forward things like remote patient monitoring and sophisticated wearable devices that capture their vital signs and combine it with the human touch—bringing it directly into our patients’ homes.” Clinical laboratories that support providers in the states Advocate Health serves may want to contact Best Buy Health. (Photo copyright: Advocate Health.)
Dispatching Geek Squads to Support Telehealth in Patients’ Homes
Best Buy Health brings to its collaboration with Atrium Health expertise in omnichannel business strategies, supply chain, and a platform to enable telehealth connectivity between patients and providers, as well as deploying specially trained Geek Squad agents for in-home support, according to an Atrium Health press release.
“With Atrium Health, we want to help enable healthcare at home for everyone. It’s getting the devices to the home when Atrium Health and the patient needs them,” said Deborah Di Sanzo, President of Best Buy Health.
Atrium Health sees Best Buy Health as a partner that can grow its program while addressing complex in-home technology that can be “tricky” to operate, Retail Dive reported.
“This transition that happens from discharging a patient from a hospital to the void of their home is the dark side of the moon: it’s disconnected, confusing, expensive. What we’ve been doing in the past is working through our hospital-at-home program and putting together a lot of these devices,” Rasu Shrestha, MD, Executive Vice President and Chief Innovation and Commercialization Officer at Advocate Health, told Fierce Healthcare.
“By working with Best Buy Health, we’re developing the seamless connected care experience and an opportunity to truly scale this,” he added.
Supporting hospital-at-home services in collaboration with Atrium Health will be a new role for at least some members of the Geek Squad. “They won’t necessarily be the same team that’s doing your home theater. They will be Geek Squad agents specially trained in health to deliver specific services in the home,” said Deborah Di Sanzo, President of Best Buy Health. (Photo copyright: Best Buy.)
Best Buy’s Healthcare Acquisitions and Growth in Hospital-at-Home Programs
Current Health, a remote monitoring care-at-home platform, in 2021.
While Best Buy was busy acquiring healthcare companies, more HaH programs popped up across the US due in part to rising inpatient costs and providers’ need to be more efficient and resourceful.
Atrium Health started its Hospital-at-Home program in March 2020 as a way to care for COVID-19 patients. The HaH program now serves people with:
According to Healthcare Dive, Shrestha claimed Atrium’s HaH program “has served more than 6,300 patients and freed 25,000 hospital bed days since it launched in March 2020,” and produced clinical outcomes that were “the same or better” when compared to the health systems’ own hospitals, and with higher patient satisfaction scores.
“We anticipate the partnership will combine Atrium Health operational and clinical expertise with Best Buy Health’s technical and logistical expertise to allow us to scale the program to 100 patients at a time and beyond within our market,” Shrestha told Healthcare Dive. “When you put that into context, this would be the equivalent of having an additional mid-sized hospital and have a real impact on capacity in our bricks-and-mortar facilities.”
Taking Atrium’s HaH Program Nationwide
According to federal Centers for Medicare and Medicaid Services predictions, healthcare spending will reach $6.8 trillion by 2030. This might explain why Best Buy increased its investment in healthcare at the same time its sales declined 9.3% in the fourth quarter of 2022 amid softening consumer demand for electronics, Reuters reported.
And, according to Forbes, though financial terms on the Best Buy/Atrium Health partnership were not released, additional investments are planned to “scale [Atrium’s HaH program] beyond the system.”
“We combine our omnichannel, Geek Squad, caring centers, and Current Health services to enable care,” Di Sanzo told Forbes. “At scale, no other company has the holistic combination of resources that when combined, will change the lives of consumers and enable them to heal right in their own home surrounding by the people and things they love the most. Those strengths, combined with Atrium Health’s extensive clinical expertise and deep experience leading in virtual care, will help us improve and enable care in the home for everyone.”
Clinical Laboratory Testing at Home
Clearly there are opportunities for clinical laboratories to support providers who treat patients in their homes. Lab leaders may want to reach out to colleagues who are planning HaH programs in partnership with Best Buy Health, Atrium Health, or other companies around the nation launching similar hospital-at-home programs.
As medical laboratories address staffing challenges, HaH strategies for performing blood tests and other diagnostics on patients in their homes could lead to important new revenue.
New lawsuit contends that the promissory notes Holmes allegedly issued on behalf of defunct clinical laboratory company Theranos are now overdue
Just weeks before Elizabeth Holmes is scheduled to begin her prison term for conviction in the federal investor fraud case related to now-defunct clinical laboratory company Theranos, the long-running legal saga of the former company founder/CEO continues to bring new twists.
This time, news emerged via a lawsuit that Holmes allegedly owes $25 million to Theranos creditors. CNBC obtained a copy of the suit and detailed its contents in a March 17 case update.
Theranos ABC, a company set up on behalf of the creditors, alleged in the lawsuit that “Holmes has not made any payments on account of any of the promissory notes,” CNBC reported. The suit was filed in Superior Court of California Count of Santa Clara.
Elizabeth Holmes (above), founder and former CEO of clinical laboratory company Theranos with husband Billy Evans of Evans Hotels. Holmes lives with Evans and the couple’s two children in the area near San Jose, California. Holmes gave birth to her second baby in February, according to People. In January, Holmes was convicted on three counts of wire fraud and one count of conspiracy. In addition to restitution, Holmes has been ordered to spend up to 11 years and three months in prison. (Photo copyright: Axios.)
Holmes Allegedly Issued Three Promissory Notes
The complaint stated that Holmes allegedly executed the following three promissory notes while she was still CEO at Theranos:
August 2011 in the amount of $9,159,333.65.
December 2011 in the amount of $7,578,575.52.
December 2013 in the amount of $9,129,991.10.
A promissory note is a written promise to pay a party a certain sum of money with a specified due date for the repayment of principal and interest.
“Theranos ABC has demanded payment of promissory note one and promissory note two from Holmes, but Holmes has failed to pay any amounts on account of promissory note,” according to the lawsuit, CNBC reported. The first two notes are overdue, and the third note is due in December.
Elizabeth Holmes’ Prison Term Could Be Delayed
News of the lawsuit, which was filed in December 2022, came to light at a court hearing on March 17. During that hearing, Judge Edward Davila heard arguments about whether Holmes should remain free pending her appeal. She is otherwise scheduled to report to prison on April 27 to begin her sentence after being convicted in January 2022 of defrauding Theranos investors.
Davila, who oversaw Holmes’ criminal case, is expected to issue a decision about her freedom during the appeal early this month. The judge is also weighing options for Holmes to pay restitution to her victims.
Prosecutors have asked that she pay back $878 million to Theranos’ former investors and other victims, according to court records reviewed by Dark Daily. The government has argued in court papers that Holmes continues to live a wealthy lifestyle despite her claiming she has no meaningful assets since the collapse of Theranos and her trial.
“Defendant has lived on an estate for over a year where, based upon the monthly cash flow statement defendant provided to the US Probation Office, monthly expenses exceed $13,000 per month,” according to court documents filed by prosecutors ahead of the March 17 hearing. “Defendant asserted that her partner pays the monthly bills rather than her but also listed her significant other’s salary as ‘$0.’”
Holmes’ attorneys argued that the government cannot take an “all or nothing” approach to restitution, and that payments should only be made to investors who testified during the trial, the Associated Press reported.
For Victims, Full Restitution Can Be Rare
The federal Department of Justice (DOJ) acknowledges in its overview of restitution that victims often never collect what they are owed by guilty parties.
“The chance of full recovery is very low,” the DOJ notes. “Many defendants will not have sufficient assets to repay their victims. Many defendants owe very large amounts of restitution to a large number of victims. In federal cases, restitution in the hundreds of thousands or millions of dollars is not unusual. While defendants may make partial payments toward the full restitution owed, it is rare that defendants are able to fully pay the entire restitution amount owed.”
Clinical laboratory professionals will note the irony that one of the biggest convicted fraudsters in US history is now largely attempting to avoid punishments associated with her crimes. If Judge Davila agrees to let Holmes remain free pending her appeal, she could stay out of prison for years and perhaps not have to pay restitution for that length of time as well.
The coming weeks will prove to be pivotal in the final outcome of the case.
It’s not just radiology. Gen Z residents will be matching in pathology and other specialties, and that means clinical laboratories should be ready to adapt their recruiting and training to Gen Z’s unique characteristics
It’s a big event in medical schools across the nation when it is time for residency programs to match residency candidates with first-year and second-year post-graduate training positions. But this year has a special twist because—for example in radiology—this is the first class of Generation Z (Gen Z) residency candidates to be matched with radiology residency programs.
In their abstract, the authors wrote, “This year, the radiology community will experience the beginning of a generational change by matching its first class of Generation Z residents. To best welcome and embrace the changing face of the radiology workforce, this Viewpoint highlights the values that this next generation will bring, how radiologists can improve the way they teach the next generation, and the positive impact that Generation Z will have on the specialty and the way radiologists care for patients.”
Members of Gen Z are now entering the workforce in large numbers. To recruit high-quality candidates from this generation, healthcare employers—including clinical laboratories and pathology practices—may have to adapt the way they interact with and train these individuals.
Gen Z is generally described as individuals who were born between 1995 and 2012. Also known as “Zoomers,” the demographic comprises approximately 25% of the current population of the United States. They are extremely diverse, tend to be very socially conscious, and can easily adapt to rapid changes in communications and education, according to the AJR paper.
Although the paper deals with radiology, this type of information can also be valuable to clinical laboratories as Gen Z pathologists are poised to enter clinical practice in growing numbers. This marks the beginning of the professional laboratory careers of Zoomers, while Millennials move up into higher levels of lab management, the oldest Gen Xers near retirement age, and Baby Boomers retire out of the profession.
“Gen Z employees bring unique values, expectations, and perspectives to their jobs,” said Paul McDonald (above), Senior Executive Director at staffing firm Robert Half in a news release. “They’ve grown up in economically turbulent times, and many of their characteristics and motivations reflect that.” Thus, clinical laboratories may have to develop methods for recruiting and training Gen Z staff that match the unique characteristics of Gen Z candidates. (Photo copyright: LinkedIn.)
Zoomers Like Digital and Artificial Intelligence Technology
One of the most unique aspects of Gen Z is that they have never lived in a world without the Internet and have little memory of life without smartphones. Zoomers grew up totally immersed in digital technology and tend to be comfortable using digital tools in their everyday life and in the workplace. They lean towards being very open to artificial intelligence (AI) and how it can assist humans in analysis and diagnostic methods.
“This group of professionals has grown up with technology available to them around the clock and is accustomed to constant learning,” said Paul McDonald, Senior Executive Director at staffing firm Robert Half in a news release. “Companies with a solid understanding of this generation’s values and preferences will be well prepared to create work environments that attract a new generation of employees and maximize their potential.”
According to the AJR paper, Zoomers learn best by doing, so employers should concentrate on interactive learning opportunities, such as simulations, virtual reality, and case-based methods for teaching the aspects of the job. They are likely to expect digital and blended resources as well as traditional approaches to learning their new job responsibilities.
The paper goes on to state that Gen Z members value diversity, equity, inclusivity, sustainability, civic engagement, and organizational transparency. Their social consciousness and diversity may yield a greater range of perspectives and problem-solving approaches which may bolster their sensitivity to patient-centered care.
“The oldest in Gen Z have already seen a recession and a war on terrorism. They’ve seen politics at its worst. And now they’ve seen a global pandemic and are about to see recession again,” said David Stillman, founder of GenGuru, a boutique management consulting firm that provides insights on how best to connect with Baby Boomers, Generation X, Millennials, and Gen Z, in an interview with the Society for Human Resource Management (SHRM). “They are survivors,” he added.
According to the SHRM, “Stillman says Millennials, who preceded Generation Z, were coddled by their parents. He maintains that Generation Z’s parents were more truthful, telling their offspring, ‘You’re going to have a really tough time out there, you have to work super hard,’ which he says created ‘the most competitive generation in the workforce since the Baby Boomers.’”
Gen Z Wants More than a Paycheck, They Want Purpose
The American Journal of Roentgenology paper also states that Gen Z members grew up in a rapidly changing world and tend to be resilient, adaptable, and flexible. They have experienced and witnessed many stressors and navigate these issues by focusing on mental health and a meaningful work-life balance. With respect to a profession, they are searching for more than just a paycheck, and they want a purposeful career where they feel a sense of belonging.
Increase information sharing and transparency to help alleviate fear and anxiety.
Incentivize them by showing them clear paths to career progression.
Make sure they know how their individual contributions matter to the organization.
Motivate them by giving them room for autonomy and experimentation.
Provide specific and constructive feedback.
Harness community and in-person interactions to boost professional collaborations.
Prioritize wellness and mental health.
“Be prepared to spend time with them face to face,” McDonald stated. “They want to be mentored and coached. If you coach them, you’re going to retain them.”
Preparing to Attract Gen Z to Clinical Laboratories
As Generation Z comes of age, more of them will be working in the medical professions. Clinical laboratories and anatomic pathology groups would be well advised to prepare their businesses by adjusting leadership, adapting recruiting efforts, and shifting marketing to attract Zoomers and remain relevant and successful in the future.
Although sweeping statements about individual generations may be limiting, understanding their unique insights, values, and backgrounds can be helpful in the workplace. With a large amount of Gen Z workers now transitioning from college into careers, it will be beneficial for clinical laboratory managers to recognize their unique characteristics to recruit and maintain talented workers more effectively.
As reimbursement for digital pathology services starts to potentially become a reality, more hospital, clinical laboratory, and reference lab leaders will explore the technology.
Do you know where to start with implementing a digital pathology program for your hospital, health system, or independent pathology group to make the best use of your budget?“Digital Pathology Implementation Strategies,” hosted by Dark Daily and sponsored by Hamamatsu, aired May 10, 2023, and is now available for free streaming.
Pathologists, hospital executives, and lab leaders need help cutting through frequently published news and commentary about digital pathology. They will find this new webinar practical and incisive for gaining a foothold on what to do for digital pathology should regulatory and reimbursement decisions rapidly evolve in favor of greater digital pathology adoption in the U.S.
Pathology is in a time of rapid change. Use this free, 60-minute Dark Daily webinar as a practical update and an essential tool.
W. Dean Wallace, MD, is a Professor of Pathology at the Keck School of Medicine at University of Southern California (USC). Dr. Wallace’s ongoing work in informatics and digital pathology includes collaborative efforts in radiology and pathology correlation and implementation of digital pathology into standard pathology practice workflows. Other areas of research include creation of novel pathology staining techniques using machine learning technology.
Orly Ardon, PhD, MBA, is the Director of Digital Pathology Operations at Memorial Sloan Kettering Cancer Center’s Pathology Department and the Scientific Operations Investigator at the Warren Alpert Center for Digital and Computational Pathology. Dr. Ardon is leading the digital scanning team and operations of the different scanning initiatives and collaborations at MSKCC. Her research interests include digital pathology technologies, laboratory process improvements, and healthcare economics.
• Understand key workflow aspects of the components needed in a digital pathology service • Gain an understanding of common limitations of commercial digital pathology products • Clarify how to structure your digital pathology implementation team • Learn a goal-based approach to develop your business case for digital pathology implementation in hospitals, health systems, and independent pathology groups
Orly Ardon, PhD, MBA, is the Director of Digital Pathology Operations at Memorial Sloan Kettering Cancer Center’s Pathology Department and the Scientific Operations Investigator at the Warren Alpert Center for Digital and Computational Pathology. Dr. Ardon is leading the digital scanning team and operations of the different scanning initiatives and collaborations at MSKCC. Her research interests include digital pathology technologies, laboratory process improvements, and healthcare economics.
