Doctors report difficulty differentiating COVID-19 from other viral infections, impacting clinical laboratory test orders
Because the SARS-CoV-2 coronavirus is in the same family of viruses that cause the common cold and influenza, virologists expected this virus—which caused the global COVID-19 pandemic—would evolve and mutate into a milder form of infection. Early evidence from this influenza season seems consistent with these expectations in ways that will influence how clinical laboratories offer tests for different respiratory viruses.
While new variants of the SARS-CoV-2 virus continue to appear, indications are that early in this flu season individuals infected with the more recent variants are experiencing milder symptoms when compared to the last few years. Doctors report they find it increasingly difficult to distinguish COVID-19 infections from allergies or the common cold because patients’ symptoms are less severe, according to NBC News.
This, of course, makes it challenging for doctors to know the most appropriate clinical laboratory tests to order to help them make accurate diagnoses.
“It isn’t the same typical symptoms that we were seeing before. It’s a lot of congestion, sometimes sneezing, usually a mild sore throat,” Erick Eiting, MD, Vice Chair of Operations for Emergency Medicine at Mount Sinai Hospital in New York City, told NBC News. “Just about everyone who I’ve seen has had really mild symptoms. The only way that we knew that it was COVID was because we happened to be testing them.” Knowing which tests for respiratory viruses that clinical laboratories need to perform may soon be the challenge for doctors. (Photo copyright: Mt. Sinai.)
Milder COVID-19 Symptoms Follow a Pattern
Previous hallmarks of a COVID-19 infection included:
Loss of taste,
loss of smell,
dry cough,
fever,
sore throat,
diarrhea,
body aches,
headaches.
However, physicians now observe milder symptoms of the infection that follow a distinct pattern and which are mostly concentrated in the upper respiratory tract.
Grace McComsey, MD, Vice President of Research and Associate Chief Scientific Officer at University Hospitals Health System (UH) in Cleveland, Ohio, told NBC News that some patients have described their throat pain as “a burning sensation like they never had, even with Strep in the past.”
“Then, as soon as the congestion happens, it seems like the throat gets better,” she added.
In addition to the congestion, some patients are experiencing:
headache,
fever,
chills,
fatigue,
muscle aches,
post-nasal drip.
McComsey noted that fatigue and muscle aches usually only last a couple of days, but that the congestion can sometimes last a few weeks. She also estimated that only around 10-20% of her newest COVID patients are losing their sense of smell or taste, whereas early in the pandemic that number was closer to 60-70% of her patients.
Doctors also noted that fewer patients are requiring hospitalization and that many recover without the use of antivirals or other treatments.
“Especially since July, when this recent mini-surge started, younger people that have upper respiratory symptoms—cough, runny nose, sore throat, fever and chills—99% of the time they go home with supportive care,” said Michael Daignault, MD, an emergency physician at Providence Saint Joseph Medical Center in Burbank, California.
Milder SARS-CoV-2 Variants Should Still be Taken Seriously
Doctors have varying opinions regarding why the current COVID-19 variants are milder. Some believe the recent variants simply aren’t as good at infecting the lungs as previous variants.
“Overall, the severity of COVID-19 is much lower than it was a year ago and two years ago,” Dan Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, told NBC News. “That’s not because the variants are less robust. It’s because the immune responses are higher.”
McComsey added that she doesn’t think mild cases should be ignored as she is still seeing new cases of long COVID with rapid heart rate and exercise intolerance being among the most common lingering symptoms. Re-infections also add to the risks associated with long COVID.
“What we’re seeing in long COVID clinics is not just the older strains that continue to be symptomatic and not getting better—we’re adding to that number with the new strain as well,” McComsey said. “That’s why I’m not taking this new wave any less seriously.”
Clinical Laboratory COVID-19 Testing May Decrease
According to Andrew Read, PhD, Interim Senior Vice President for Research and Evan Pugh University Professor of Biology and Entomology at Pennsylvania State University, there is nothing unexpected or startling about the coronavirus acquiring new mutations.
“When a mutation confers an interesting new trick that’s got an advantage, it’s going to be popping up in many different places,” Read told the New York Times. “Everything we see is just consistent with how you imagine virus evolution proceeding in a situation where a new virus has jumped into a novel host population.”
Data from the Centers for Disease Control and Prevention’s COVID-19 Data Tracker—which reports weekly hospitalizations, deaths, emergency department (ED) visits, and COVID-19 test positivity results—shows infection trends fluctuating, but overall, they are decreasing.
For the week of October 21, 2023, there were 16,186 hospitalizations due to COVID-19 compared to the highest week recorded (January 15, 2022) with 150,674 hospitalizations nationwide.
The highest number of deaths reported in a single week were 25,974 for the week of January 8, 2021, while 637 patients perished from COVID-19 during the week of October 21, 2023.
In January of 2021, COVID accounted for 13.8% of all ED visits and in October 2023, COVID-19 was responsible for 1.3% of ED visits.
“What I think we’re seeing is the virus continuing to evolve, and then leading to waves of infection, hopefully mostly mild in severity,” Barouch told The New York Times.
As severity of COVID-19 infections continues to fall, so, presumably, will demand for COVID-19 testing which has been a source of revenue for clinical laboratories for several years.
Many clinical laboratory professionals are aware of the significant amount of waste going into landfills from spent COVID-19 rapid PCR tests that use biosensors to produce results. These biosensor systems “use printed circuit boards, or PCBs, the same materials used in computers. PCBs are difficult to recycle and slow to biodegrade, using large amounts of metal, plastic, and non-eco-friendly materials,” according to a Penn Engineering Today blog post.
UPenn’s new test does not use PCBs. Instead, its biosensor uses “bacterial cellulose (BC), an organic compound synthesized from several strains of bacteria,” the blog post noted.
“This new BC test is non-toxic, naturally biodegradable and both inexpensive and scalable to mass production, currently costing less than $4.00 per test to produce. Its cellulose fibers do not require the chemicals used to manufacture paper, and the test is almost entirely biodegradable,” the blog post continued.
“There is a need for biodegradable diagnostic testing,” said Cesar de la Fuente, PhD (above), Presidential Assistant Professor in the Psychiatry Department at the University of Pennsylvania’s Perelman School of Medicine. “We will be continuing to perfect this technology, which could hopefully help many people in the future, while also looking to expand it to other emerging pathogens in anticipation of future pandemics.” Clinical laboratories engaged in SARS-CoV-2 testing during the COVID-19 pandemic can attest to the massive amounts of waste generated by traditional PCR testing. (Photo copyright: University of Pennsylvania.)
Evolution of Improvement for SARS-CoV-2 Diagnostic Assays
Cesar de la Fuente, PhD, is Presidential Assistant Professor in the Psychiatry Department at the Perelman School of Medicine. His lab has been hard at work since the start of the pandemic to improve COVID-19 testing. The recent study was a collaboration between University of Pennsylvania’s de la Fuente Lab and William Reis de Araujo, Professor in Analytical Chemistry at the State University of Campinas (UNICAMP) in São Paulo, Brazil.
De Araujo leads the Portable Chemical Sensors Lab and has been pairing his electrochemistry expertise with de la Fuente’s lab for years, Penn Engineering Today noted.
The team wanted to combine the speed and cost-effectiveness of previous rapid tests with an eco-friendly biodegradable substrate material.
Bacterial cellulose (BC) was a great choice because it “naturally serves as a factory for the production of cellulose, a paper-like substance which can be used as the basis for biosensors,” Penn Engineering Today reported.
Additionally, BC has an excellent track record for a variety of uses, such as regenerative medicine, wound care, and point-of-care (POC) diagnostics, the blog post noted. UPenn’s test offers speed and accuracy without needing costly equipment making it desirable for clinical laboratories preparing to fight the next pandemic.
The test has shown to be capable of “correctly identifying multiple variants in under 10 minutes. This means that the tests won’t require ‘recalibration’ to accurately test for new variants,” Penn Engineering Today added.
Innovation Born from Inspiration
Though rapid tests are essential to help curb the spread of COVID-19, the negatives that come with these tests didn’t sit well with the UPenn team. This spurred them to strive for improvements.
PCR tests “are hampered by waste [metal, plastic, and the aforementioned PCBs]. They require significant time [results can take up to a day or more] as well as specialized equipment and labor, all of which increase costs,” Penn Engineering Today noted.
Additionally, “Sophistication of PCR tests makes them harder to tweak and therefore slower to respond to new variants,” the blog post concluded.
“There’s a tension between these two worlds of innovation and conservation,” de la Fuente told Penn Engineering Today. “When we create new technology, we have a responsibility to think through the consequences for the planet and to find ways to mitigate the environmental impact.”
Need for Biodegradable Diagnostic Tests
“COVID-19 has led to over 6.8 million deaths worldwide and continues to affect millions of people, primarily in low-income countries and communities with low vaccination coverage,” the Cell Reports Physical Science paper noted.
“There is a need for biodegradable diagnostic testing,” de la Fuentes told Penn Engineering Today. “We will be continuing to perfect this technology, which could hopefully help many people in the future, while also looking to expand it to other emerging pathogens in anticipation of future pandemics.”
While UPenn’s test will require clinical trials and FDA approval before it can become available to clinical laboratories and for point-of-care testing, it promises a bright, eco-friendly future for rapid viral testing.
Free at home clinical-laboratory testing for COVID-19 has been provided in the past, but this time the federal government wants to manufacture as many tests as possible in the US
Pathologists and clinical laboratory managers may be interested to learn that the US market is about to be flooded with millions of at-home COVID-19 rapid tests. The federal government has contracted with 12 US-based test manufacturers to produce 200 million at-home self-tests aimed at detecting “currently circulating COVID-19 variants” through the end of this year, according to a US Department of Health and Human Services (HHS) news release.
Federal officials want to head off “supply chain issues” that developed in the past with reliance on tests made overseas, and to address a possible COVID-19 surge during the fall and winter, the Associated Press (AP) reported.
In fact, 500 million tests have already been distributed through US government channels to long-term care facilities, schools, and low-income senior housing.
“Manufacturing COVID-19 tests in the United States strengthens our preparedness for the upcoming fall and winter seasons, reduces our reliance on other countries, and provides good jobs to hardworking Americans,” said Assistant Secretary for Preparedness and Response Dawn O’Connell, JD (above), in an HHS news release. “ASPR’s investments in these domestic manufacturers will increase availability of tests in the future.” With the federal government preparing for what it expects to be a surge in demand for COVID-19 testing, clinical laboratories may want to track the CDC’s weekly reports on the number of positive COVID-19 cases as this year’s influenza season progresses. (Photo copyright: Administration for Strategic Preparedness and Response.)
In Vitro Diagnostics Test Makers Get Government Gigs
This is not the first time federal officials sent out free COVID-19 tests to consumers. According to the AP, more than 755 million tests went out to US households in previous efforts to fight the spread of infections. But unlike those tests, these tests will be manufactured entirely within the US.
The government’s latest wave of free tests is meant to “complement ASPR’s ongoing distribution of free COVID-19 tests to long-term care facilities, low-income senior housing, uninsured individuals, and underserved communities, with 500 million tests provided to date through these channels,” the HHS news release noted.
Both large and lesser-known in vitro diagnostics (IVD) manufacturers were selected by the federal government to receive funding. They include:
HHS advises people to take the test at the first sign of symptoms (fever, sore throat, runny nose, others), after coming into contact someone who has COVID-19, or prior to gathering with a group, as a preventative to spread of the coronavirus.
Reporting laboratories say existing antibodies work against the BA.2.86 variant.
The variant does not appear to be linked in the US with increasing infections or hospitalizations.
It is “unclear how easily BA.2.86 spreads” relative to other variants.
BA.2.86 has been detected in nine states: Colorado, Delaware, Michigan, Ohio, Pennsylvania, Virginia, Washington, and in wastewater in New York and Ohio, as well as in other countries.
For week ending Sept. 23, the CDC reported the following statistics compared to the prior week:
19,079 COVID-19 hospitalizations, down 3.1%.
Total hospitalizations: 6.3 million.
2.7% of total deaths were due to COVID-19, up 8%.
COVID-19 test positivity rate was 11.6%, down 1.1%.
1.8% of emergency department visits were diagnosed with COVID-19, down 11.7%.
According to Verywell Health, BA.2.86 carries more than 30 mutations.
“Even with a lot of mutations, there are a lot of spots in the virus that can be recognized by our immune system, and there are many shared mutations as well. There will be some protection from new vaccine booster as well as prior infections,” Rajendram Rajnarayanan, PhD, Assistant Dean of Research and Associate Professor, Basic Sciences, Arkansas State University, told Verywell Health.
It’s worth noting that the common cold, influenza, SARS, and SARS-CoV-2 are all in the coronavirus family, and thus closely related with similar symptoms. It would not be a surprise that SARS-CoV-2 joins those other viruses as an endemic virus with a similar yearly cycle of infection rates.
If that happens, and no surge in infections appears that would motivate orders for the new COVID-19 at-home tests, the government may find itself with a lot of unused tests at the end of the year. The US Food and Drug Administration (FDA) is aware of this possibility and provides a website where people can check to see if their test has an extended expiration date.
Plus, folks who are tired of the pandemic may not respond at all to the government’s insistence to prepare for possible surges in infection rates.
“Whether or not people are done with it, we know the virus is there, we know that it’s circulating. We know, if past is prologue, it’ll circulate to a higher degree and spread, and cases will go up in the fall and winter seasons,” said Assistant Secretary for Preparedness and Response Dawn O’Connell, JD, in the HHS new release. “Anticipating that that would be true again, or something similar, we want to make sure the American people have these tools.”
Clinical laboratories may want to prepare as well. Many people are not comfortable with at-home self-testing and prefer to have their local medical labs perform the tests.
Certainly every clinical laboratory in the United States has a unique story about dealing with the challenges of the SARS-CoV-2 outbreak, but only BioReference did testing for multiple professional sports leagues and the cruise ship industry
Few would challenge the assertion that the nation’s clinical laboratories (along with public health officials) were caught flat-footed when the SARS-CoV-2 coronavirus reached the United States in the winter of 2021. Even as the federal Centers for Disease Control and Prevention (CDC) and some labs rushed to develop reliable medical laboratory tests for COVID-19 in the early weeks of the outbreak, the demand for tests far outstripped supply in this country for many months.
This was the moment when the pandemic’s need meant lab testing opportunity for medical laboratories across the nation. This was particularly true for Elmwood Park, New Jersey-based BioReference Laboratories, Inc. (BRLI), a division of OPKO, Inc. BioReference found itself in the nation’s first pandemic hot zone—New York City and surrounding counties.
Not only was this lab company geographically in the center of the first overwhelming surge of COVID-19 cases, but its management team had important relationships across government and business. For that reason, its management team was pulled into the earliest planning sessions by government officials at the city, state, and federal level.
Consequently, in the earliest days of the outbreak, BioReference was one of the nation’s first labs to help organize and support drive-through COVID-19 specimen collection centers. Its management team went on to accomplish many notable firsts in the lab’s response to the pandemic. All of this is described in the recently-published book “Swab–Leadership in the Race to Provide COVID Testing to America.”
As CEO of BioReference Laboratories during the time of the COVID-19 pandemic in 2020 and 2021, physician Jon R. Cohen, MD (above), energized his clinical lab’s management team and staff to rise to a series of unique challenges, ranging from helping set up the nation’s first drive-through COVID-19 sampling sites in New York City to performing testing for professional sports leagues, such as the NBA, the NFL, and the NHL. (Photo copyright: New York Foundling, Inc.)
Harnessing the Creativity and Energy of a Clinical Lab Staff
The book’s author is Jon R. Cohen, MD, who was CEO of BioReference Laboratories throughout the course of the pandemic. Cohen is now CEO of Talkspace, a virtual behavioral health company.
“Swab” documents BioReference lab’s response to the SARS-CoV-2 pandemic and tells the tale of how the lab company harnessed the creativity of its managers and lab scientists to speedily build up daily test volumes at a time when automation, analyzers, test kits, collection supplies, and reagents were in short supply.
Clinical laboratory professionals interested in lab management will gain valuable insights from Cohen’s approach to writing “Swab.”
While describing BioReference lab’s many innovative COVID-19 testing services, Cohen also provides readers with the management lessons and insights he used to impart needed skills to the company managers, while also inspiring BioReference Lab’s staff to devote the extra effort necessary to deliver COVID-19 testing in novel ways and in unusual settings.
When New York City hospitals were overwhelmed by cases in the earliest days of the pandemic, Cohen’s personal contacts with political leaders came into play. Just a few years earlier, Cohen had run for statewide office as a Democrat. He had friendships with the New York City Mayor Bill de Blasio, with the New York State Governor Mario Cuomo, and with Senators Charles Schumer and Kirsten Gillibrand.
Cohen’s Lab Had a Seat at Government Planning Tables
As these government officials convened various task forces to address the pandemic, Cohen describes how BioReference had a seat at the table and a voice in viable ways to organize specimen collection and COVID-19 testing literally overnight and on an unprecedented scale.
The pandemic’s early days in late February, March, and April of 2020 were only the first challenges to be overcome by the management at BioReference. “Swab” describes a remarkable progression of innovative SARS-CoV-2 testing programs initiated by Cohen and his team. Each of these testing programs was tailored to the specific needs of different industries. No other clinical laboratory organization in the United States was as successful at serving this range of clients. For example:
For the last eight games of the National Basketball Association’s 2020 season and playoffs, BioReference created and managed the NBA’s “biosecure bubble” program at Disney World in Orlando. Over the course of 172 games, 150,000 SARS-CoV-2 tests were performed with zero-positivity.
The National Football League watched the NBA play in its bubble that summer. BioReference got the call and worked with NFL management to provide COVID-19 tests. For the 2020 season, in support of 268 games played across the United States, BioReference performed 1.23 million tests for 5,000 players, coaches, and staff, with an infection rate of less than 1%.
Along with the NBA and NFL, BioReference provided SARS-CoV-2 testing for professional soccer and hockey, the Winter X Games, and the US men’s and women’s Olympic soccer teams.
One of the lab company’s more complex SARS-CoV-2 testing programs involved the cruise ship industry. In 2021, BioReference established sites in 13 ports around the US and the Caribbean. The lab placed staff on as many as 24 cruise ships at one time.
Of course, testing for schools, colleges, universities, and employers was part of BRLI’s testing services over the course of the COVID-19 pandemic as well.
Creativity of Clinical Lab Managers and Staff
As the examples above illustrate, “Swab” will give readers a ringside seat in how BioReference Laboratories harnessed the creativity and skills of its management team and staff to address the unprecedented demands for timely, accurate COVID-19 testing from the very beginning of the pandemic through its waning months.
Cohen writes with an accessible style and provides readers with an easy-to-read narrative of his lab company’s journey through the pandemic. Each of the book’s 10 chapters ends with a “Leadership Reflection” that Cohen uses to describe the management methods he utilized to keep BRLI’s thousands of employees on task and on time, so that the end result month after month was “mission accomplished.”
In today’s digital age, the statement “this book is available at a bookstore near you” may not be applicable. What is true is that author Jon R. Cohen’s “Swab–Leadership in the Race to Provide COVID Testing to America” can be ordered at Amazon.com, Alibris.com, and other web-based booksellers.
Little-known Polish company relied on suspect arbitration court to demand thousands of euros from conference speakers
Clinical laboratory and pathology professionals may want to heed the phrase “caveat emptor” (“let the buyer beware”) if invited to speak at events organized by little-known entities. That appears to be the lesson from a rather bizarre story coming out of Poland involving scholars from multiple countries who agreed to speak during a series of online COVID-19 webinars and who were later billed thousands of euros for their participation.
But months after the event, the organizer demanded payment for the researchers’ participation, and in some cases, turned to a Polish arbitration court to enforce the demand. But in a curious twist, the legitimacy of that court has itself been called into question.
“I was interested in the topic, and I agreed to participate,” Björn Johansson, MD, told Science. “I thought it was going to be an ordinary academic seminar. It was an easy decision for me.” Johansson, a physician and researcher at the Karolinska Institute in Sweden, has since “come to regret that decision,” the publication reported.
Villa Europa is now seeking €80,000 ($86,912 in current US dollars) from Johansson, including legal costs and interest, after turning to a Swedish court. Others have received demands for €13,000 to €25,000 ($14,123 to $27,156) in fees, late payment penalties, and court costs, Science reported.
Researchers Axel Brandenburg, PhD (left), and Björn Johansson, MD (right), are two of the 32 scholars from six countries who are now being billed thousands of euros for their participation in the Villa Europa COVID-19 modeling webinars. Pathology and clinical laboratory leaders who receive similar invitations may want to thoroughly read the contracts before agreeing to participate. (Photo copyright: Axel Brandenburg, Björn Johansson.)
How Did It All Happen?
According to Science, the ordeal began when an individual named Matteo Ferensby invited the scientists to speak at the webinars. His email signature indicated an affiliation with the University of Warsaw, but the university “has no employee by that name, according to the institution’s press office,” Science reported, adding that “there is no track record of scientific publications from a Matteo Ferensby.”
By one speaker’s count, the company produced at least 11 webinars between April 2020 and June 2021. “The speakers themselves—about 10 people in each session—were the only audience, but participants were told the recordings would be published open access afterward,” Science reported.
Ferensby did not disclose that speakers would be charged conference fees. In fact, one speaker was told explicitly that no fees would be requested, Science noted.
However, the speakers were later asked to sign a license agreement that would allow the organizer to publish the recordings. It included a clause on the last page stating that they would have to pay fees of €790 and €2785 (US$859 and $3,029) related to publication.
The financial amounts were written in words rather than numbers with no highlighting, according to Science, which reviewed some of the contracts.
“Many of the speakers, already busy studying COVID-19 and under pressure from the transition to remote teaching, did not notice these clauses,” Science reported. Said one speaker: “The contract was unreadable [but] I eventually sent it.”
Questionable Arbitration
Some of the webinar participants told Science that they later received altered versions of the contracts with “an additional page where the fees are made explicit, and [with] modified clauses, one of them stating that disputes can be settled by a Polish arbitration court.”
“In my opinion this is fraud,” Durlik said. Nevertheless, Villa Europa used alleged rulings by PESA to go after some of the speakers in their own local courts.
“For the researchers now under pressure from the courts, ignoring the demands is not an option,” Science reported. “They have all submitted court filings supporting their case.”
The speakers claim that “the demands are illegitimate and that they were deceived about what they were signing in the contracts,” Science noted. One speaker, Axel Brandenburg, PhD, of the Nordic Institute for Theoretical Physics (NORDITA), is awaiting a ruling in September, Science reported.
Warnings against Predatory Conferences
The story comes amid increasing concerns about so-called “predatory conferences,” in which scientists are invited under false pretenses to participate in what appear to be legitimate meetings.
“Would-be attendees should expect missing plenary speakers, multiple fields of research smashed together in a Frankenstein program, and an absence of the important academic rigor that fuels the conferences that scientists know and love,” wrote senior science writer Ruairi J. Mackenzie in Technology Networks. “The companies organizing these events are motivated by profit above all else.”
Mackenzie offered several tips to help both speakers and attendees spot fake conferences:
Examine the promotional materials. “Whether you are studying an unprompted email or a conference webpage, look for shoddy writing quality or outlandish layouts.”
Check with your colleagues. “The dominant conferences in your field are probably in that position because they have proved time and time again that they can deliver a valuable experience for attendees.”
Look at other conferences from the same producer. If a company produces a high volume of conferences on a wide range of topics, that can be a sign that the quality will be shoddy, he suggested.
Look at the contact information. A legitimate conference should have ties to an established society or conference organizer. Get the address, and then look at that location in Google Street View to see if it’s the kind of building where you’d expect a legitimate company to be located.
The experience of these 32 scientific and medical scholars demonstrates that there is always a new twist in how honest citizens can be defrauded. For that reason, clinical laboratory managers and pathologists should be wary when approached by unknown organizations with speaking invitations, particularly in Europe.
