FDA says the move will make it easier to gain authorization for other clinical laboratory tests to utilize at-home collection kits
In another sign of how diagnostic testing is responding to changing consumer preferences, the US Food and Drug Administration (FDA) granted marketing authorization to LetsGetChecked for the company’s Simple 2 test for chlamydia and gonorrhea, which includes at-home collection of samples sent to the test developer’s clinical laboratories in the US and in Ireland.
This marks the first time the FDA has cleared a diagnostic test for either condition in which samples are collected at home. It’s also the first test with at-home sample collection to be authorized for any sexually transmitted infection (STI) other than HIV, the FDA said in a new release.
Samples are collected through a vaginal swab or urine sample. “Results are delivered online in approximately 2-5 days with follow-up virtual consultations and treatment available if needed,” the company press release states.
Previously authorized tests for the conditions required sample collection at the point of care. The company also offers telehealth and online pharmacy services.
“This authorization marks an important public health milestone, giving patients more information about their health from the privacy of their own home,” said Jeff Shuren, MD, JD (above), Director of the FDA’s Center for Devices and Radiological Health. “We are eager to continue supporting greater consumer access to diagnostic tests, which helps further our goal of bringing more healthcare into the home.” With this emphasis on at-home testing from the FDA, clinical laboratories in the US and Ireland will likely be processing more at-home collected samples. (Photo copyright: FDA.)
Simple 2 Process and Costs
Prior to collecting the sample, the user goes online to complete a questionnaire and activate the kit, the FDA news release notes.
LetsGetChecked, headquartered in New York City and Dublin, Ireland, says its US labs are CLIA– and CAP-certified. The company currently offers more than 30 at-home tests covering STIs, men’s health, women’s health, and COVID-19, at prices ranging from $89 to $249 per test.
The Simple 2 test costs $99, and is not covered by insurance, Verywell Health reported. Consumers can get discounts by subscribing to quarterly, semiannual, or annual tests.
New Regulatory Pathway
The FDA said it reviewed the test under its De Novo regulatory pathway, which is intended for “low- to moderate-risk devices of a new type,” according to the news release.
“Along with this De Novo authorization, the FDA is establishing special controls that define the requirements related to labeling and performance testing,” the agency stated. “When met, the special controls, in combination with general controls, provide a reasonable assurance of safety and effectiveness for tests of this type.”
This creates a new regulatory classification, the agency said, that will make it easier for similar devices to obtain marketing authorization.
Citing data from the federal Centers for Disease Control and Prevention (CDC), the FDA news release states that chlamydia and gonorrhea are the most common bacterial STIs in the US. The CDC estimates that there were 1.6 million cases of chlamydia and more than 700,000 cases of gonorrhea in 2021.
“Typically, both infections can be easily treated, but if left untreated, both infections can cause serious health complications for patients, including infertility,” the news release states. “Expanding the availability of STI testing can help patients get quicker results and access to the most appropriate treatment, ultimately helping to curb the rising rates of STIs.”
Experts Praise the FDA’s Authorization of the Lab Test
STI experts contacted by STAT said they welcomed the FDA’s move.
“There are many people who would like to be tested for STIs who may not know where to go or who have barriers to accessing medical care,” said Jodie Dionne, MD, Associate Professor of Medicine in the University of Alabama at Birmingham (UAB) Division of Infectious Diseases. “If we are going to do a better job of reaching more sexually active people for STIs … we need to be creative about how to get them tested and treated in a way that is highly effective and works for them.”
Family physician Alan Katz, MD, a professor at the University of Hawaii John A Burns School of Medicine, told STAT that the Hologic assay is also used by clinicians who treat people in remote locations to diagnose STIs and is regarded as being highly accurate.
“This option is exceptionally useful for individuals who live in rural areas or are geographically distanced from a clinic where STI testing can be done and there is no telehealth option available,” he told STAT.
With this latest move, the FDA is recognizing that it is time to give consumers more control over their healthcare. This is a signal to clinical laboratories that they should be developing their own strategies and offerings that serve consumers who want to order their own tests. Of course, many states still require a physician’s signature on lab test orders, but that is likely to change over time.
Experts cite high vaccination rates and behavioral changes among at-risk groups, but warn about complacency; clinical laboratories should remain vigilant
In July, Scott Gottlieb, MD, Commissioner of the US Food and Drug Administration (FDA) from May 2017 to April 2019, wrote an op-ed in The New York Times titled, “Monkeypox Is About to Become the Next Public Health Failure.” In it, he wrote, “Our country’s response to monkeypox has been plagued by the same shortcomings we had with COVID-19.” But has it improved? Clinical laboratory leaders and pathology group managers will find it informative to find out what has taken place since Gottlieb made his stark prediction.
The global monkeypox outbreak that emerged last spring appears to have subsided in the US and Europe, though it remains to be seen if the disease can be completely eradicated, according to multiple media reports. As of Oct. 26, 2022, the Centers for Disease Control and Prevention (CDC) reported a 7-day rolling average of 30 cases per day in the US, down from a peak of nearly 440/day in early August.
Cases are also down in cities that earlier reported heavy outbreaks. For example, the New York City Health Department reported a 7-day average of just two cases per day on Oct. 25, compared with 73/day on July 30.
And the San Francisco Department of Public Health announced on Oct. 20 that it would end the city’s public health emergency on monkeypox (MPX) effective on Oct. 31. “MPX cases have slowed to less than one case per day and more than 27,000 San Franciscans are now vaccinated against the virus,” the agency stated in a press release.
“Once again, we caution that a declining outbreak can be the most dangerous outbreak, because it can tempt us to think that the crisis is over and to let down our guard,” said World Health Organization (WHO) Director-General Tedros Adhanom Ghebreyesus, PhD, in an Oct. 12 global press briefing. “That’s not what WHO is doing. We are continuing to work with countries around the world to increase their testing capacity, and to monitor trends in the outbreak.” Clinical laboratories should not assume the outbreak has passed but continue to be vigilant and prepared for increased demand in monkeypox testing. (Photo copyright: ITU Pictures.)
Changing Behavior Lowers Infection Rates
In addition to high vaccination rates, public health experts have attributed the decline to behavioral changes among at-risk groups. “There were really substantial changes among men who have sex [with] men,” infectious disease physician Shira Doron, MD, of Tufts Medical Center in Boston, told ABC News.
On September 2, the CDC published the results of a survey indicating that about half of men who have sex with men “reported reducing their number of sex partners, one-time sexual encounters, and use of dating apps because of the monkeypox outbreak.”
Another likely factor is the disease’s limited transmissibility. “Initially, there was a lot of concern that monkeypox could spread widely at daycares or in schools, but, overall, there has been very little spread among children,” NPR reported.
But citing multiple studies, the NPR story noted “that often there isn’t very much virus in the upper respiratory tract,” where it might spread through talking or coughing. “Instead, the highest levels of virus occur on sores found on the skin and inside the anus.”
These studies, along with earlier research, “explain why monkeypox is spreading almost exclusively through contact during sex, especially anal and oral sex, during the current outbreak,” NPR reported.
Monkeypox Could Mutate, experts say
Despite the promising numbers, public health experts are warning that monkeypox could remain as a long-term threat to public health. According to an article in Nature, “At best, the outbreak might fizzle out over the next few months or years. At worst, the virus could become endemic outside Africa by reaching new animal reservoirs, making it nearly impossible to eradicate.”
In addition to the limited transmissibility of the virus, Nature noted that the outbreak stems from a relatively mild form of the pathogen and is rarely fatal. As of Oct. 28, the CDC reported a total of just six confirmed deaths in the US out of a total of 28,302 confirmed cases since the first infections were reported in May.
It is possible that the virus could mutate into a more contagious form, but Nature noted that monkeypox is a DNA virus, and that they tend to mutate more slowly than RNA viruses such as SARS-CoV-2 and HIV. Nevertheless, University of Alabama at Birmingham School of Medicine bioinformatician Elliot Lefkowitz, PhD, warned that a “worrisome mutation” could arise if the outbreak continues for much longer.
“I have no confidence that all the people who need to be tested are being tested,” she told Nature. She expressed concerns that people could resume risky behavior if they think the danger has passed.
Another question is whether currently available vaccines offer long-lasting protection. And though reported case numbers are down in the US and Europe, they are rising in parts of Africa and South America, Nature noted.
Gottlieb’s Dire Prediction
The decline in new infections followed dire warnings last summer about the possible consequences of the outbreak. In his New York Times op-ed, former Gottlieb criticized the CDC for being slow to test for the virus. He wrote, “[I]f monkeypox gains a permanent foothold in the United States and becomes an endemic virus that joins our circulating repertoire of pathogens, it will be one of the worst public health failures in modern times not only because of the pain and peril of the disease but also because it was so avoidable.”
At the time of his writing, Gottlieb was right to be concerned. On July 29, the CDC reported a seven-day moving average of 390 reported cases per day. According to the federal agency, a reported case “Includes either the positive laboratory test report date, CDC call center reporting date, or case data entry date into CDC’s emergency response common operating platform, DCIPHER.”
Quashing the outbreak, Gottlieb estimated, would have required about 15,000 tests per week among people presenting symptoms resembling monkeypox. But between mid-May and the end of June, he noted, the CDC had tested only about 2,000 samples, according to the federal agency’s July 15 Morbidity and Mortality Weekly Report (MMWR).
As a remedy, Gottlieb called on the Biden administration to re-focus the CDC’s efforts more on disease control “by transferring some of its disease prevention work to other agencies,” including the FDA.
Though only in early stages, findings could lead to a ‘therapeutic against current and newly-arising variants,’ say researchers
As SARS-CoV-2 changes and mutates, some therapeutic antibodies that were once highly effective in fighting the virus have lost potency. But now, in a proof-of-concept study, researchers from Boston Children’s Hospital have identified one antibody that neutralizes all known variants of the coronavirus, including the omicron variant. Microbiologists and clinical laboratory managers will find this intriguing, as most medical labs perform serology testing for SARS-CoV-2 antibodies.
The new antibody appears to be robust. It triggers several other types of antibodies as part of the immune response. If validated by further research, this discovery, the researchers state, may lead to new vaccines, better therapies, and improved treatments for COVID-19.
“We hope that this humanized antibody will prove to be as effective at neutralizing SARS-CoV-2 in patients as it has proven to be thus far in preclinical evaluations,” said geneticist Frederick Alt, PhD, Director of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital and one of the leaders of the research. Clinical laboratories that perform serology testing for COVID-19 will be intrigued by this new line of research. (Photo copyright: PR Newswire.)
SP1-77 Antibody Outperforms All Others at Neutralizing SARS-CoV-2
To conduct their research, the team used genetically modified mice that basically have built-in human immune systems. These mice were originally utilized for seeking out antibodies to HIV, another virus that tends to mutate. Their immune systems can mimic what human immune systems encounter when a viral invader attacks.
The scientists inserted two human gene segments into the mice, which quickly produced antibodies resembling those made by humans. The mice were then exposed to the SARS-CoV-2 spike protein from the original coronavirus strain. The scientists found that the mice produced nine different families of antibodies that could bind to the spike protein.
The researchers then tested the effectiveness of those antibodies and found that three of the nine antibody families strongly neutralized the original SARS-CoV-2 coronavirus. In addition, one of the antibody families—dubbed SP1-77—was much more powerful and could neutralize the Alpha, Beta, Gamma, Delta, and all known Omicron strains of the SARS-CoV-2 virus.
New Monoclonal Antibody Products and Vaccines
If their findings are validated through further research, SP1-77 “would have potential to be a therapeutic against current and newly-arising variants of concern” according to the Science Immunology study. It also could be useful as part of a cocktail containing other antibody treatments for COVID-19 variants.
“SP1-77 binds the spike protein at a site that so far has not been mutated in any variant, and it neutralizes these variants by a novel mechanism,” said Tomas Kirchhausen, PhD, Senior Investigator, Program in Cellular and Molecular Medicine at Boston Children’s Hospital and one of the authors of the study in a statement announcing the study findings. “These properties may contribute to its broad and potent activity,” he added.
“This is very early-stage proof-of-concept work to illustrate that broadly neutralizing antibodies can be generated using a mouse model,” Amesh Adalja, MD, an infectious disease expert and senior scholar at the Johns Hopkins Center for Health Security, told Prevention. “Such work, if replicated and expanded, could form the basis of new monoclonal antibody products as well as a vaccine.”
The researchers have applied for a patent for the SP1-77 antibody as well as the mouse model they used to create it. Studies on the antibody are ongoing and have only been performed on mice and not humans. The scientists intend to execute further research on the innovative antibody and hope it will someday be used to help fight the COVID-19 virus and all its variants.
“We’d love to have a vaccine that is active against all circulating variants, including those yet to come,” Thomas Russo, MD, Professor and Chief of Infectious Disease, Department of Medicine, University at Buffalo told Prevention. “It’s the holy grail of vaccines.”
Microbiologists and clinical laboratories working with monoclonal antibodies to treat for COVID-19 infections will no doubt want to follow the Boston Children’s Hospital research closely as it may lead to new treatments and vaccines.
There are reports of phlebotomists refusing to draw monkeypox blood samples and social stigma surrounding the disease can affect who gets a medical laboratory test
Cases of monkeypox are increasing in the US—14,115 as of Aug. 19, up 1,400 from the prior week—and clinical laboratories around the country are bracing for a potential increase in monkeypox testing orders.
Several factors, however, are affecting the testing. Chief among them:
Lab workers refusing to take blood draws from potential monkeypox patients, and
Community clinics in some cities having to delay other care to deal with an onslaught of monkeypox test orders.
Here are five trends clinical laboratory leaders should be aware of that are influencing the state of monkeypox testing in the country.
Trend 1: Some Phlebotomists Refuse to Draw Possible Monkeypox Specimens
CNN reported that phlebotomists at two of the largest commercial laboratories—Labcorp and Quest Diagnostics—were either refusing or being told not to draw blood samples from suspected monkeypox patients.
“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.”
In “Medical Laboratories Respond to Monkeypox Outbreak Using CDC-Developed Diagnostic Test,” Dark Daily noted that skin lesion swabbing, such as that necessary to perform the OrthopoxvirusPCR test, is the preferred method to check for monkeypox because of higher viral counts in the lesions. However, physicians may order follow-up blood tests for confirmed monkeypox patients, and suspected patients may need bloodwork as part of other routine care.
In an update posted on its website, Quest noted it has been testing swab specimens of skin lesions for monkeypox, but those swabs are performed by providers and not Quest. However, the company was also preparing to take blood draws of possible monkeypox patients in its patient service centers.
“Given that monkeypox has been declared a national public health emergency and the most recent CDC guidance, we are now implementing procedures to safely enable patients with suspected or confirmed monkeypox infection into our patient service sites for phlebotomy blood draws and other non-swab specimen collections,” Quest stated. “This approach will enable patients with suspected or confirmed monkeypox infections to receive additional testing they may need.”
Trend 2: Guidance Is Available to Help Lab Workers Avoid Monkeypox Infection
The CDC has posted guidance to maintain infection control around suspected monkeypox specimens. Among the steps noted by the agency:
Lesion specimens from patients suspected of having monkeypox will carry the highest quantity of the virus. When possible, lab workers that have a smallpox vaccination from within the last three years should handle these specimens. Smallpox vaccination also protects from monkeypox in many cases. Unvaccinated workers who test suspected monkeypox specimens need to take extra precautions, such as wearing a buttoned lab coat, gloves, and face protection, and avoiding splashes, the CDC stated.
Blood specimens draw from suspected monkeypox patients will have a low quantity of the virus. Lab workers testing these specimens do not need to be vaccinated for monkeypox, but standard precautions should be followed.
Before using automated testing platforms with suspected monkeypox specimens, labs should conduct a risk assessment to identify potential hazards.
Trend 3: Monkeypox Testing Gains an Early Social Stigma
Some people who need to be tested for monkeypox may be hesitant to seek out a medical laboratory or patient service center because of a stigma being attached to the disease.
Although it does not match the early hysteria associated with HIV infections in the 1980s—in a 1987 poll, 60% of respondents said AIDS patients should carry a card identifying them as such, Gallup noted—there have been clear instances where people and agencies have associated monkeypox infection with men having sex with other men.
“The focus for all countries must be engaging and empowering communities of men who have sex with men to reduce the risk of infection and onward transmission, to provide care for those infected, and to safeguard human rights and dignity,” Tedros Adhanom Ghebreyesus, PhD, the Director-General at the World Health Organization, said in a July 27 media briefing.
Ghebreyesus added that while 98% of monkeypox infections have been among men who have sex with men, anyone can get the disease, including children.
“Stigma and discrimination can be as dangerous as any virus, and can fuel the outbreak,” said Tedros Adhanom Ghebreyesus, PhD (above), Director-General at the World Health Organization (WHO), in a media briefing. Clinical laboratories would be wise to prepare for a marked increase in demand for monkeypox testing. (Photo Copyright: WHO/Christopher Black.)
“Men who have sex with men have been hit the hardest by monkeypox to date, but LGBTQ+ health advocates say improper messaging risks branding monkeypox as a ‘gay disease,’ eroding effective preventive measures and allowing the virus to spread,” Bloomberg Law reported.
For example, 66% of respondents either were not sure or did not believe there is a vaccine for monkeypox.
Trend 4: Workers Who Refuse to Test Patients for Monkeypox Face Possible Backlash
Some medical professionals have raised concerns about healthcare workers being unwilling to test monkeypox patients.
“This is absolutely inexcusable. It’s a grave dereliction of duty,” David Harvey, Executive Director of the National Coalition of STD Directors, told CNN. The group represents sexually transmitted disease (STD) directors at public health departments in the US.
“For every single patient that walks [through] your door, you use universal precautions because every disease doesn’t have a phenotype or outward appearance, so you have to treat everyone exactly the same,” Garfield Clunie, MD, president of the National Medical Association and Assistant Professor of Obstetrics, Gynecology, and Reproductive Science at the Icahn School of Medicine at Mount Sinai, told Bloomberg Law. “You can’t treat someone differently because of their sexual orientation, or race, or gender, or for any other reason.”
Trend 5: Public Clinics Show Early Signs of Monkeypox Testing Pressure
A survey of 80 public health departments conducted by the National Coalition of STD Directors indicated that some sites may already be getting overwhelmed by demand for monkeypox testing.
According to the survey results, 79% of public health clinics saw an increased demand for monkeypox testing over the past four weeks. In a troubling aspect, 28% of clinics said they could not meet testing demand if it increases.
Further, 22% of clinics have reduced screenings for other STDs to prioritize monkeypox testing. Such moves likely delay patients from receiving other care they need.
Clinical laboratories may want to take note of the survey findings. The pressure public health clinics currently face could be a precursor to similar problems at labs if demand for monkeypox testing grows.
Given the large number of mutations found in the SARS-CoV-2 Omicron variant, experts in South Africa speculate it likely evolved in someone with a compromised immune system
As the SARS-CoV-2 Omicron variant spreads around the United States and the rest of the world, infectious disease experts in South Africa have been investigating how the variant developed so many mutations. One hypothesis is that it evolved over time in the body of an immunosuppressed person, such as a cancer patient, transplant recipient, or someone with uncontrolled human immunodeficiency virus infection (HIV).
One interesting facet in the story of how the Omicron variant was being tracked as it emerged in South Africa is the role of several medical laboratories in the country that reported genetic sequences associated with Omicron. This allowed researchers in South Africa to more quickly identify the growing range of mutations found in different samples of the Omicron virus.
“Normally your immune system would kick a virus out fairly quickly, if fully functional,” Linda-Gail Bekker, PhD, of the Desmond Tutu Health Foundation (formerly the Desmond Tutu HIV Foundation) in Cape Town, South Africa, told the BBC.
“In someone where immunity is suppressed, then we see virus persisting,” she added. “And it doesn’t just sit around, it replicates. And as it replicates it undergoes potential mutations. And in somebody where immunity is suppressed that virus may be able to continue for many months—mutating as it goes.”
Multiple factors can suppress the immune system, experts say, but some are pointing to HIV as a possible culprit given the likelihood that the variant emerged in sub-Saharan Africa, which has a high population of people living with HIV.
Li “was among the first to detail extensive coronavirus mutations in an immunosuppressed patient,” the LA Times reported. “Under attack by HIV, their T cells are not providing vital support that the immune system’s B cells need to clear an infection.”
Linda-Gail Bekker, PhD (above), of the Desmond Tutu Health Foundation cautions that these findings should not further stigmatize people living with HIV. “It’s important to stress that people who are on anti-retroviral medication—that does restore their immunity,” she told the BBC. (Photo copyright: Test Positive Aware Network.)
Omicron Spreads Rapidly in the US
Genomics surveillance Data from the CDC’s SARS-CoV-2 Tracking system indicates that on Dec. 11, 2021, Omicron accounted for about 7% of the SARS-CoV-2 variants in circulation, the agency reported. But by Dec. 25, the number had jumped to nearly 60%. The data is based on sequencing of SARS-CoV-2 by the agency as well as commercial clinical laboratories and academic laboratories.
Experts have pointed to several likely factors behind the variant’s high rate of transmission. The biggest factor, NPR reported, appears to be the large number of mutations on the spike protein, which the virus uses to attach to human cells. This gives the virus an advantage in evading the body’s immune system, even in people who have been vaccinated.
“The playing field for the virus right now is quite different than it was in the early days,” Joshua Schiffer, MD, of the Fred Hutchinson Cancer Research Center, told NPR. “The majority of variants we’ve seen to date couldn’t survive in this immune environment.”
One study from Norway cited by NPR suggests that Omicron has a shorter incubation period than other variants, which would increase the transmission rate. And researchers have found that it multiplies more rapidly than the Delta variant in the upper respiratory tract, which could facilitate spread when people exhale.
Using Genomics Testing to Determine How Omicron Evolved
But how did the Omicron variant accumulate so many mutations? In a story for The Atlantic, virologist Jesse Bloom, PhD, Professor, Basic Sciences Division, at the Fred Hutchinson Cancer Research Center in Seattle, described Omicron as “a huge jump in evolution,” one that researchers expected to happen “over the span of four or five years.”
Hence the speculation that it evolved in an immunosuppressed person, perhaps due to HIV, though that’s not the only theory. Another is “that the virus infected animals of some kind, acquired lots of mutations as it spread among them, and then jumped back to people—a phenomenon known as reverse zoonosis,” New Scientist reported.
Still, experts are pointing to emergence in someone with a weakened immune system as the most likely cause. One of them, the L.A. Times reported, is Tulio de Oliveira, PhD, Affiliate Professor in the Department of Global Health at the University of Washington. Oliveira leads the Centre for Epidemic Response and Innovation at Stellenbosch University in South Africa, as well as the nation’s Network for Genomic Surveillance.
The Network for Genomic Surveillance, he told The New Yorker, consists of multiple facilities around the country. Team members noticed what he described as a “small uptick” in COVID cases in Gauteng, so on Nov. 19 they decided to step up genomic surveillance in the province. One private clinical laboratory in the network submitted “six genomes of a very mutated virus,” he said. “And, when we looked at the genomes, we got quite worried because they discovered a failure of one of the probes in the PCR testing.”
Looking at national data, the scientists saw that the same failure was on the rise in PCR (Polymerase chain reaction) tests, prompting a request for samples from other medical laboratories. “We got over a hundred samples from over thirty clinics in Gauteng, and we started genotyping, and we analyzed the mutation of the virus,” he told The New Yorker. “We linked all the data with the PCR dropout, the increase of cases in South Africa and of the positivity rate, and then we began to see it might be a very suddenly emerging variant.”
Oliveira’s team first reported the emergence of the new variant to the World Health Organization, on Nov. 24. Two days later, the WHO issued a statement that named the newly classified Omicron variant (B.1.1.529) a “SARS-CoV-2 Variant of Concern.”
Microbiologists and clinical laboratory specialists in the US should keep close watch on Omicron research coming out of South Africa. Fortunately, scientists today have tools to understand the genetic makeup of viruses that did not exist at the time of SARS 2003, Swine flu 2008/9, MERS 2013.
