Clinical laboratories nationwide could follow Yale’s example and enact programs to bring much needed lab services to traditionally underserved communities
Ever since the COVID-19 pandemic drove up demand for telehealth medical services, mobile clinical laboratories have grown in popularity as well, especially among residents of remote and traditionally underserved communities. Now, several divisions of Yale University are getting in on the trend.
“Using a van retrofitted with laboratory-grade diagnostic equipment, the mobile clinic will employ SalivaDirect—a saliva-based COVID-19 PCR test developed at YSPH—to facilitate on-site testing with a turnaround time of two to three hours,” Yale Daily News reported.
Funded by a federal grant, the initial goal was to provide 400 free COVID-19 tests, but the program has exceeded that number. By April 10, the mobile lab had been deployed more than 60 times, appearing at events and pop-up sites throughout various communities in Connecticut, including regular stops at the WHEAT Food Pantry of West Haven.
“[The clinical laboratory-in-a-van] is a brilliant way to reduce the barriers to testing, instead taking the lab to communities who may be less likely—or unable—to access the necessary clinic or labs,” microbiologist Anne Wyllie, PhD, a research scientist who helped develop the PCR test deployed by the mobile lab told Yale Daily News. Wyllie works in the Department of Epidemiology of Microbial Diseases at Yale School of Public Health. “We are actively working with our community partners to identify how we can best serve their communities,” she added. (Photo copyright: Yale School of Medicine.)
Mobile Lab’s Capabilities
Collecting samples, processing, and delivering same-day COVID-19 results was the initial goal but that plan has expanded, Yale School of Medicine noted in a news release.
“Same-day onsite delivery of test results is an added benefit for communities and individuals without access to Wi-Fi or the ability to receive private health information electronically,” Yale added.
The mobile van is staffed with trained clinical laboratory technicians as well as community health navigators who provide both healthcare information and proper follow-up connections as needed for patients who receive positive COVID-19 results. The van runs off power from outdoor electrical outlets at each location and currently serves historically underserved populations in Hartford, Middlesex, Fairfield, New Haven, and New London counties, Yale noted.
“The van allows us to bring our services, as well as healthcare information, directly to communities where they are needed,” said Angelique Levi, MD, Associate Professor, Vice Chair and Director of Pathology Reference Services, and CLIA Laboratory Medical Director in the Department of Pathology at Yale University School of Medicine in a news release.
Launch of a High Complexity Molecular Lab on Wheels
YPL and YSPH collaborated to make the mobile lab a reality. YSPH created the saliva-based COVID-19 test and YPL “provided clinical validation necessary to get the testing method ready for emergency use authorization by the US Food and Drug Administration,” Yale noted.
“YPL recognized the need to be closer to the front lines of patient care and that retrofitting a fully licensed, high complexity molecular laboratory into a consumer-sized van was the right next step,” Chen Liu, MD, PhD, Chair of the Department of Pathology at Yale School of Medicine, noted in a Yale news release. This “gives us options to efficiently deliver accurate diagnostic information when and where it’s needed,” he added.
Throughout the COVID-19 pandemic, the Connecticut Department of Public Health, the City of New Haven, and various community organizations partnered with YPL, YSPH, and the SalivaDirect team to offer free SARS-CoV-2 testing to the public at two different sites in New Haven.
Principal investigators Levi and microbiologist Anne Wyllie, PhD, who helped develop the PCR test deployed by the mobile, lab led the Yale lab-in-a-van research project.
Flambeau Diagnostics, a biomedical company that specializing in mobile lab testing, worked with the Yale team to design and implement the mobile lab van.
“According to Wyllie, the new YSPH and YPL initiative utilizes one of the former Flambeau vans that had been retrofitted for clinical testing,” a Yale news release noted.
Kat Fajardo, Laboratory Manager at Yale University, added custom pieces of equipment to ensure seamless PCR testing. One was a Magnetic Induction Cycler (Mic) measuring only six by six inches. The Mic allowed for measurement of 46 biological specimens, while it’s diminutive size freed up space on the van’s countertop. This allowed lab techs to process specimens concurrently while also providing COVID-19 testing, according to a Yale news release.
Additionally, the van has a Myra portable robotic liquid handler which is “designed to automate the process of moving clinical specimens between vials,” the news release notes.
“What we wanted to do is run high complexity testing in the van, with a reduced timeframe, and then be able to get the results out to the patients as soon as we possibly could,” Fajardo stated.
Exploring the Mobile Laboratory’s Potential
According to a news release, YPL and YSPH consult with community partners to select locations for the mobile lab to visit. These partners include:
APT Foundation (New Haven County, in addition to others.
Although the van was initially used to provide SalivaDirect COVID-19 testing to vulnerable populations, YPL is working with its partners in those communities to identify other testing needs beyond COVID.
The Yale team is considering additional offerings and support such as the addition of a social worker as well as expanding lung health awareness beyond COVID-19 to other respiratory diseases. Also under consideration:
Vaccinations including for COVID-19 and Hepatitis B, and
Health education and materials for harm reduction and STI prevention, a Yale news release noted.
Yale’s Laboratory-in-a-Van program is a consumer-facing effort that is bringing much needed clinical lab services to traditionally underserved communities in Connecticut. Clinical laboratories throughout the nation could do the same with remote or homebound patients who cannot reach critical care.
The federal agency shipped tests to five commercial clinical laboratory companies, augmenting efforts by public health labs
Medical laboratories in the US are ramping up their efforts to respond to an outbreak of monkeypox that has been spreading around the globe. Microbiologists and clinical laboratory scientists will be interested to learn that this infectious agent—which is new to the US—may be establishing itself in the wild rodent population in this country. If proved to be true, it means Americans would be at risk of infection from contact with rodents as well as other people.
The Centers for Disease Control and Prevention (CDC) announced on May 18 that it had identified the infection in a Massachusetts resident who had recently traveled to Canada. As of August 3, the federal agency was reporting 6,617 confirmed cases in the US.
“Because there are no other non-variola orthopoxviruses circulating in the US, a positive test result is presumed to be monkeypox,” states the APHL press release.
“As we focus on the US response, we keep a close watch on the global outbreak. Infectious diseases don’t respect borders, as we know,” said Chris Mangal (above), director of public health preparedness and response, APHL, in a press release. “I am proud of how LRN member laboratories have rapidly and effectively responded to this emergency. This is precisely what the LRN was intended to do. Should this outbreak continue to grow, preparing for expanded testing and increasing capacity beyond LRN laboratories is important to ensuring we are ready for a surge in testing.” (Photo copyright: Association of Public Health Laboratories.)
Commercial Labs Get Involved
Seeking to bolster testing capacity, the federal Department of Health and Human Services (HHS) announced on June 22 that the CDC had begun shipping OrthopoxvirusPCR tests to five commercial lab companies. They include:
“By dramatically expanding the number of testing locations throughout the country, we are making it possible for anyone who needs to be tested to do so,” said HHS Secretary Xavier Becerra in an HHS press release.
Labcorp was first out of the gate, announcing on July 6 that it was offering the CDC-developed test for its customers, as well as accepting overflow from public labs. “We will initially perform all monkeypox testing in our main North Carolina lab and have the capacity to expand to other locations nationwide should the need arise,” said Labcorp chief medical officer and president Brian Caveney, MD, in a press release.
Mayo Clinic Laboratories followed suit on July 11, announcing that the clinic’s Department of Laboratory Medicine and Pathology would perform the testing at its main facility in Rochester, Minnesota.
“Patients can access testing through Mayo Clinic healthcare professionals and will soon be able to access testing through healthcare professionals who use Mayo Clinic Laboratories as their reference laboratory,” Mayo stated in a press release.
Then, Quest Diagnostics announced on July 13 that it was testing for the virus with an internally developed PCR test, with plans to offer the CDC test in the first half of August.
The lab-developed test “was validated under CLIA federal regulations and is now performed at the company’s advanced laboratory in San Juan Capistrano, Calif.,” Quest stated in a press release.
Public Health Emergency?
Meanwhile, the CDC announced on June 28 that it had established an Emergency Operations Center to respond to the outbreak. A few weeks later, on July 23, World Health Organization (WHO) Secretary-General Tedros Adhanom Ghebreyesus, PhD, declared that the outbreak represented “a public health emergency of international concern.”
He noted that international health regulations required him to consider five elements to make such a declaration.
“WHO’s assessment is that the risk of monkeypox is moderate globally and in all regions, except in the European region where we assess the risk as high,” he said in a WHO news release. “There is also a clear risk of further international spread, although the risk of interference with international traffic remains low for the moment. So, in short, we have an outbreak that has spread around the world rapidly, through new modes of transmission, about which we understand too little, and which meets the criteria in the International Health Regulations.”
Still, public health authorities have made it clear that this is not a repeat of the COVID-19 outbreak.
“Monkeypox virus is a completely different virus than the viruses that cause COVID-19 or measles,” the CDC stated in a June 9 advisory. “It is not known to linger in the air and is not transmitted during short periods of shared airspace. Monkeypox spreads through direct contact with body fluids or sores on the body of someone who has monkeypox, or with direct contact with materials that have touched body fluids or sores, such as clothing or linens. It may also spread through respiratory secretions when people have close, face-to-face contact.”
The New York Times reported that some experts disagreed with the CDC’s assessment that the virus “is not known to linger in the air.” But Professor of Environmental Health Donald Milton, MD, DrPH, of the University of Maryland, told The Times it is still “not nearly as contagious as the coronavirus.”
The Massachusetts resident who tested positive in May was not the first known case of monkeypox in the US, however, previous cases involved travel from countries where the disease is more common. Two cases in 2021—one in Texas and one in Maryland—involved US residents who had recently returned from Nigeria, the CDC reported. And a 2003 outbreak in the Midwest was linked to rodents and other small mammals imported to Texas from Ghana in West Africa.
“Labcorp and Quest don’t dispute that in many cases, their phlebotomists are not taking blood from possible monkeypox patients,” according to CNN. “What remains unclear, after company statements and follow-ups from CNN, is whether the phlebotomists are refusing on their own to take blood or if it is the company policy that prevents them. The two testing giants say they’re reviewing their safety policies and procedures for their employees.”
One symptom of monkeypox, the CDC states, is a rash resembling pimples or blisters. Clinicians are advised that two swabs should be collected from each skin lesion, though “procedures and materials used for collecting specimens may vary depending on the phase of the rash.”
“Effective communication and precautionary measures between specimen collection teams and laboratory staff are essential to maximizing safety when manipulating specimens suspected to contain monkeypox virus,” the CDC notes. “This is especially relevant in hospital settings, where laboratories routinely process specimens from patients with a variety of infectious and/or noninfectious conditions.”
Perhaps the negative reaction to the CDC’s initial response to the COVID-19 outbreak in the US is driving the federal agency’s swift response to this new viral threat. Regardless, clinical laboratories and pathology groups will play a key role in the government’s plan to combat monkeypox in America.
InspectIR COVID-19 Breathalyzer identifies a chemical signature associated with SARS-CoV-2 in about three minutes with 91.2% sensitivity and 99.3% specificity
One company is hoping that it can make breathalyzers a viable, easier way to screen for SARS-CoV-2. It will soon have the opportunity to learn if consumers will accept this form of screening for COVID-19, as its device recently obtained an Emergency Use Authorization from the FDA.
On April 14, 2022, InspectIR Systems, LLC, of Frisco, Texas, was granted the US Food and Drug Administration’s first-ever emergency use authorization (EUA202006) for a portable breath test device designed to screen for SARS-CoV-2 infection. Clinical laboratories that perform COVID-19 testing will want to compare the high-level sensitivity of this breath test compared to rapid antigen tests currently used for COVID-19 screening.
The device is about the size of a carry-on suitcase. It provides test results in less than three minutes and is currently authorized for use with subjects who are 18 or older.
The FDA’s EUA limits use of the device to “a qualified, trained operator under the supervision of a healthcare provider licensed or authorized by state law to prescribe tests,” the federal agency said. The test “can be performed in environments where the patient specimen is both collected and analyzed, such as doctor’s offices, hospitals, and mobile testing sites.”
The InspectIR COVID-19 Breathalyzer device “is yet another example of the rapid innovation occurring with diagnostic tests for COVID-19,” said Jeffrey Shuren, MD, JD (above), director of the FDA’s Center for Devices and Radiological Health (CDRH), in the news release. A portable device that can identify SARS-CoV-2 infections in a few minutes with 91% specificity may be of great interest to clinical laboratory companies operating COVID-19 popup testing sites around the nation. (Photo copyright: US Food and Drug Administration.)
In granting the authorization, the FDA cited results of a study with 2,409 participants in which the test had sensitivity (correct positive results) of 91.2% and specificity (correct negative results) of 99.3%. “The test performed with similar sensitivity in a follow-up clinical study focused on the Omicron variant,” the agency stated.
“The FDA continues to support the development of novel COVID-19 tests with the goal of advancing technologies that can help address the current pandemic and better position the US for the next public health emergency,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health (CDRH), in the news release.
In its coverage of the EUA, CNET noted that the InspectIR breath test is more sensitive than rapid antigen tests but not as sensitive as PCR tests. The FDA advised that people who receive a positive test result with the InspectIR COVID-19 Breathalyzer should follow up with a PCR molecular test.
How the InspectIR COVID-19 Breathalyzer Works
InspectIR LLC was founded in 2017 by Tim Wing and John Redmond, Forbes reported. Their original goal was to develop a breathalyzer for detection of cannabis or opioid use. However, with the onset of the COVID-19 pandemic, the entrepreneurs decided to adapt the technology into a SARS-CoV-2 diagnostic test.
As described in the FDA’s EUA documents, a subject breathes into the device using a sterilized one-time-use straw. A pre-concentrator collects and concentrates the five targeted VOCs, all from the ketone and aldehyde families of organic compounds. These go to a Residual Gas Analyzer, and an algorithm determines whether the sample contains the chemical signature associated with a SARS-CoV-2 infection.
Redmond told Forbes that the specific mix of VOCs is proprietary. The article notes that Wing, Redmond, and Verbeck have patented the pre-concentrator technology.
The devices are manufactured at a Pfeiffer Vacuum Inc. facility in Indiana. The InspectIR founders told Forbes they expect to produce 100 units per week in a start-up phase with plans to ramp up as sales increase. They also plan to look at applications for other respiratory diseases.
InspectIR has not announced exact pricing, but Time reports that the company will lease the equipment to clients, and that pricing per test will be comparable to rapid antigen tests.
InspectIR’s first breathalyzer device is receiving much positive coverage from the media. Should it prove to effective at spotting COVID-19 at popup testing sites, it may supplant traditional clinical laboratory rapid antigen tests as the screening test of choice.
ELISA tests at Icahn School of Medicine contradict earlier studies which found that antibodies developed to combat the SARS-CoV-2 coronavirus are short-lived
Medical laboratories at the forefront of the COVID-19 pandemic will be intrigued to learn that antibodies produced by the body to combat the coronavirus infection may actually provide long-term immunity, contrary to previous studies that found otherwise.
A recent study from the Icahn School of Medicine at Mount Sinai found that the protection may be more robust than previously believed. This may surprise many clinical laboratory scientists and clinical pathologists. Since the outbreak of the pandemic, multiple studies have been published with conflicting findings about the strength of the immune response to SARS-CoV-2 and the length of immunity provided after an infection.
In a Mount Sinai news release, however, Florian Krammer, PhD, microbiologist and Professor of Vaccinology in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai, and a senior author of the paper, said, “While some reports have come out saying antibodies to this virus go away quickly, we have found just the opposite—that more than 90% of people who were mildly or moderately ill produce an antibody response strong enough to neutralize the virus, and the response is maintained for many months.”
The researchers published the findings of their study—which was based on an internally-developed antibody test—in Science.
The study concludes, “Although this cannot provide conclusive evidence that these antibody responses protect from reinfection, we believe it is very likely that they will decrease the odds ratio of reinfection and may attenuate disease in the case of breakthrough infection. We believe it is imperative to swiftly perform studies to investigate and establish a correlate of protection from infection with SARS-CoV-2.”
Florian Krammer, PhD (above), runs the Krammer Laboratory in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai in New York. He noted that the longevity and neutralizing effects of antibody response are “critically important to enabling us to effectively monitor seroprevalence in communities, and to determining the duration and levels of antibody that protect us from reinfection.” Antibody response, he added, is also “essential for effective vaccine development.” (Photo copyright: Icahn School of Medicine at Mount Sinai.)
Details of the Icahn School of Medicine Study
The study arose from an effort by Mount Sinai to identify potential donors for a convalescent plasma therapy program. Beginning in late March, the health system used an enzyme-linked immunosorbent assay (ELISA) to screen thousands of individuals for presence of antibodies to the spike protein in the SARS-CoV-2 virus. The virus uses the spike protein to bind to a receptor in host cells, the researchers noted, making it “the main, and potentially only target for neutralizing antibodies.”
Screened patients either had confirmed cases of COVID-19, as determined by a polymerase chain reaction (PCR) test, or suspected cases, “defined as being told by a physician that symptoms may be related to SARS-CoV-2 or exposure to someone with confirmed SARS-CoV-2 infection,” the researchers wrote. The Mount Sinai health system also offered the test to employees.
Samples from each person were diluted in five discrete titers (concentrations) ranging from 1:80 to 1:2880, and each was tested for detectable presence of the antibodies. This allowed the researchers to categorize the samples as low, moderate, or high:
Low titers: 1:80 or 1:160
Moderate titers: 1:320
High titers: 1:960 or >1:2880
Between the start of the program and early October, the health system screened 72,401 people, of whom 30,082 tested positive for at least the lowest levels of antibodies. Among those who tested positive, a large majority fell into the moderate or high categories:
1:80: 690 (2.29%)
1:160: 1453 (4.83%)
1:320: 6765 (22.49%)
1:960: 9564 (31.79%)
1:2880: 11610 (38.60%)
The researchers also wanted to see whether the antibodies offered actual protection against the virus. So, they selected 120 samples and ran a quantitative microneutralization assay. In the lowest of the three categories, 50% of the samples showed neutralizing activity. That rose to 90% in the moderate category and 100% in the high category.
Finally, to determine how long protection might last, the researchers recalled 121 plasma donors for additional tests at two different points during the study. The researchers reported a slight drop in antibody levels about three months after onset of symptoms, and then a larger drop after five months. But antibodies were still present in most samples.
“It is still unclear if infection with SARS-CoV-2 in humans protects from reinfection and for how long,” the researchers wrote. “We know from work with common human coronaviruses that neutralizing antibodies are induced, and these antibodies can last for years and provide protection from reinfection or attenuate disease, even if individuals get reinfected.”
Previous ‘Conflicting’ Research
As previously noted, other studies raised doubts about the longevity of the antibodies produced by the body’s immune system. For example, the Mount Sinai researchers cited a study from China published in Nature Medicine that looked at the immune responses of 37 symptomatic patients and an equal number of asymptomatic individuals with laboratory-confirmed cases of the COVID-19 disease. In the latter group, 40% had no detectable levels of IgG antibodies after eight weeks.
The study also found a decrease in neutralizing antibodies in 30 of the asymptomatic individuals (81.1%) and 23 of the symptomatic individuals (62.2%) over the same period.
However, the Mount Sinai researchers pointed out that the antibody test in the Chinese study targeted a different protein. “The same paper also reported relatively stable (slightly declining) neutralizing antibody titers, which shows much higher concordance with our present findings,” they wrote. “Thus, the stability of the antibody response over time may also depend on the target antigen.”
A different study from England saw a 26% decline in antibodies over three months, CNN reported. That study, conducted by Imperial College London and Ipsos MORI, a market research firm, was based on responses from more than 365,000 randomly selected people who had self-administered a lateral flow antibody test.
But the seemingly conflicting studies from New York and the UK may not be contradictory, CNN reported. “People’s bodies produce an army of immune compounds in response to an infection and some are overwhelming at first, dying off quickly, while others build up more slowly. Measurements that show a waning antibody response in the first months after infection might be measuring this first wave—but there’s a second team building its forces in the background.”
In the same CNN report, Ania Wajnberg, MD, Director of Clinical Antibody Testing at Mount Sinai Hospital and co-author of the Icahn Mount Sinai study, said, “The serum antibody titer we measured in individuals initially were likely produced by plasmablasts—cells that act as first responders to an invading virus and come together to produce initial bouts of antibodies whose strength soon wanes.”
She added, “The sustained antibody levels that we subsequently observed are likely produced by long-lived plasma cells in the bone marrow. This is similar to what we see in other viruses and likely means they are here to stay. We will continue to follow this group over time to see if these levels remain stable as we suspect and hope they will.”
Does this mean that most people who get infected with the COVID-19 coronavirus will retain an immunity to the disease? Maybe. In the Icahn Mount Sanai study, Florian Kramer wrote, “More than 90% of people who were mildly or moderately ill produce an antibody response strong enough to neutralize the virus, and the response is maintained for many months.”
Thus, clinical laboratories engaged in serological testing may be asked to perform follow-up antibody tests to see if we do indeed create long-term immunity to COVID-19. Further, pathologists and medical laboratory scientists will want to follow future studies published in peer-reviewed journals to see if the findings of the Mount Sinai study are replicated at other sites.
