Virus World

Machine-learning system trained on millions of human audio clips shows promise for detecting COVID-19 and tuberculosis.  A team led by Google scientists has developed a machine-learning tool that can detect and monitor health conditions by evaluating noises such as coughing and breathing. The artificial intelligence (AI) system, trained on millions of audio clips of human sounds, might one day be used by physicians to diagnose diseases including COVID-19 and tuberculosis and to assess how well a person’s lungs are functioning. This is not the first time a research group has explored using sound as a biomarker for disease. The concept gained traction during the COVID-19 pandemic, when scientists discovered that it was possible to detect the respiratory disease through a person’s cough.

What’s new about the Google system — called Health Acoustic Representations (HeAR) — is the massive data set that it was trained on, and the fact that it can be fine-tuned to perform multiple tasks. The researchers, who reported the tool earlier this month in a preprint1 that has not yet been peer reviewed, say it’s too early to tell whether HeAR will become a commercial product. For now, the plan is to give interested researchers access to the model so that they can use it in their own investigations. “Our goal as part of Google Research is to spur innovation in this nascent field,” says Sujay Kakarmath, a product manager at Google in New York City who worked on the project....

Preprint available here https://arxiv.org/pdf/2403.02522.pdf 

GETTING a cough, fever or sore throat at this time of year could be down to any number of things, from a common cold to Covid-19. With a new strain of swine flu being detected in the UK

The London Medical Laboratory said its test can be taken at 95 selected pharmacies, drop-in clinics and health stores nationwide. You can find a full list of the places they're sold here. Otherwise, you can also order the test online to be delivered to your home. Dr Narayanan said: "The current strains of flu that are circulating may produce only mild illness in one person but may cause severe symptoms and even prove fatal to others. "This is particularly important in people with pre-existing health conditions and long-term diseases. Similarly, while the RSV virus may only produce chesty cold symptoms in some people, it can severely affect elderly people and children. "All of these viruses, including swine flu, display very similar initial symptoms to the common cold, but these symptoms may quickly escalate."

Taking a test to identify which virus is causing your symptoms could bring "peace of mind" to some or ensure "they are not endangering anyone in their family this festive season", the clinical lead claimed. The fact that the UKHSA is still working to ascertain the source of the H1N2 strain spotted in the North Yorkshire resident is another reason people might want to get tested, Dr Narayanan added.

Where else can I get these test?

The 95 pharmacies and clinics aren't the only place you can take a test telling the difference between the viruses. Online pharmacy Chemist Connect sells a kit by the brand CordX that claims to test for Covid, influenza A and B and RSV. It carries a much lower price tag too - £37.95, along with a delivery charge. Granted, that's still a fair amount pay for a test. Alternatively, you can nab Flowflex Flu Test and Covid Test Bundle at your local Boots. It won't be able to test for RSV - but you'll only have to shell out £4 for the two kits that come in the bundle. You can buy a five-pack of Influenza A/B Rapid Test at Tesco for £12. You can't get a free Covid-19 PCR test any more and rapid lateral flow tests are no longer free for most people. But according to NHS guidance, you might be eligible to get them for free if:

• You have a health condition which means you're at high risk of getting seriously ill from Covid
• You work in healthcare settings or in a hospice

But the company that created the 30-minute, over-the-counter test has filed for bankruptcy, so the product’s eventual availability to consumers remains unclear. The Food and Drug Administration issued an emergency authorization for the first over-the-counter, at-home combination flu and Covid test on Friday, just two days after the company that makes the test announced that it had filed for bankruptcy protection based, in part, on the agency’s lengthy approval timeline. The single-use test works with a self-collected nasal swab and provides a result in about 30 minutes, according to the F.D.A. The test is meant to be used by people 14 and older, or by an adult collecting a sample from someone age 2 or older. The test’s developer, Lucira Health, based in California’s Bay Area, announced its bankruptcy plan on Wednesday, noting that it had expected its emergency-use authorization for the test in August before the onslaught of the flu season. The company said the agency’s authorization process “became protracted,” and said it had high expenditures as it moved forward with manufacturing the combination tests. Without revenue that the company expected from projected sales of the tests during this year’s flu season, Lucira decided that it would pursue a sale of its business but continue operations to serve customers, according to its news release. The bankruptcy plan was reported earlier in The Wall Street Journal.

Background

Throughout the COVID-19 pandemic, testing individuals remains a key action. One approach to rapid testing is to consider the olfactory capacities of trained detection dogs.

Methods

Prospective cohort study in two community COVID-19 screening centers. Two nasopharyngeal swabs (NPS), one saliva and one sweat samples were simultaneously collected. The dog handlers (and the dogs…) were blinded with regards to the Covid status. The diagnostic accuracy of non-invasive detection of SARS-CoV-2 infection by canine olfaction was assessed as compared to nasopharyngeal RT-PCR as the reference standard, saliva RT-PCR and nasopharyngeal antigen testing.

Results

335 ambulatory adults (143 symptomatic and 192 asymptomatic) were included. Overall, 109/335 participants tested positive on nasopharyngeal RT-PCR either in symptomatic (78/143) or in asymptomatic participants (31/192). The overall sensitivity of canine detection was 97% (95% CI, 92 to 99) and even reached 100% (95% CI, 89 to 100) in asymptomatic individuals compared to NPS RT-PCR. The specificity was 91% (95% CI, 72 to 91), reaching 94% (95% CI, 90 to 97) for asymptomatic individuals. The sensitivity of canine detection was higher than that of nasopharyngeal antigen testing (97% CI: 91 to 99 versus 84% CI: 74 to 90, p = 0.006), but the specificity was lower (90% CI: 84 to 95 versus 97% CI: 93 to 99, p = 0.016).

Conclusions

Non-invasive detection of SARS-CoV-2 infection by canine olfaction could be one alternative to NPS RT-PCR when it is necessary to obtain a result very quickly according to the same indications as antigenic tests in the context of mass screening.

Published in PLOS One (June 1, 2022):

https://doi.org/10.1371/journal.pone.0268382

Canines seem to detect coronavirus infections with remarkable accuracy, but researchers say large-scale studies are needed before the approach is scaled up. Asher is an eccentric, Storm likes sunbathing and Maple loves to use her brain. All three could play a part in controlling the COVID-19 pandemic, but they are not scientists or politicians. They are dogs.  And they are not alone. Around the world, canines are being trained to detect the whiff of COVID-19 infections. Dog trainers are claiming extraordinary results — in some cases, they say that dogs can detect the virus with almost perfect accuracy. Scientists involved with the efforts suggest that canines could help to control the pandemic because they can screen hundreds of people an hour in busy places such as airports or sports stadiums, and are cheaper to run than conventional testing methods such as the RNA-amplification technique PCR. But most of these findings have not yet been peer reviewed or published, making it hard for the wider scientific community to evaluate the claims. Researchers working on more conventional viral tests say that initial results from dog groups are intriguing and show promise. But some question whether the process can be scaled up to a level that would allow the animals to make a meaningful impact. On 3 November, groups working with the animals met in an online workshop called International K9 Team to share preliminary results from experiments and to improve how their research is coordinated. “No one is saying they can replace a PCR machine, but they could be very promising,” says veterinary neurologist Holger Volk at the University of Veterinary Medicine Hanover in Germany, who is leading an effort to train and study COVID-sniffing dogs and did not speak at the event.

Sense of wonder

Humans have taken advantage of canines’ superior sense of smell for decades. Dogs’ noses bear 300 million scent receptors, compared with humans’ 5 million or 6 million. That enables them to detect tiny concentrations of odour that people can’t. Sniffer dogs are already a familiar sight in airports, where they detect firearms, explosives and drugs. Scientists have also trained dogs to detect some cancers and malaria, but the animals are not routinely used for this purpose. Researchers don’t know for sure what the dogs are smelling, but many suspect that these illnesses cause the human body to let off a distinct pattern of volatile organic compounds (VOCs). These molecules readily evaporate to create scent that dogs can pick up. Previous work with non-COVID viruses has suggested that viral infections might also cause the body to do this.  Many sniffer-dog scientists turned their attention to COVID-19 early in the pandemic. They have trained their canines to smell samples, most often of sweat, in sterile containers, and to sit or paw the floor when they detect signs of infection. Trials at airports in the United Arab Emirates, Finland and Lebanon are using dogs to detect COVID-19 in sweat samples from passengers; these are then checked against conventional tests. According to data presented at the K9 meeting, dogs in Finland and Lebanon have identified cases days before conventional tests picked up the virus, suggesting that they can spot infection before symptoms start. Riad Sarkis, a surgeon and researcher at Saint Joseph University in Beirut, is part of a French–Lebanese project that has trained 18 dogs. Sarkis used the best two performers for the airport trial in Lebanon. The dogs screened 1,680 passengers and found 158 COVID-19 cases that were confirmed by PCR tests. The animals correctly identified negative results with 100% accuracy, and correctly detected 92% of positive cases, according to unpublished results. “This is very accurate, feasible, cheap and reproducible,” says Sarkis, who has been approached about using the dogs in schools, banks and prisons, and is working with a shopping mall to offer COVID-19 testing using the animals. Low-income countries with limited lab space could particularly benefit from the approach, says Isabella Eckerle, a virologist at the University Hospitals of Geneva in Switzerland....

Published in Nature (Nov. 23, 2020):

https://doi.org/10.1038/d41586-020-03149-9

An 18-year old high school senior from the Houston area mobilized his medical knowledge as one of the youngest EMTs in Texas and co-founded a mobile lab which can provide COVID-19 results in 15 minutes.  Texas Mobile Medical Labs was created to counteract testing delays that bogged down how quickly patients received results. The mobile lab currently operates in a van and a tent outside a community center in the Post Oak area for patients who prefer to come to them. For those that can't, the mobile lab can travel to any patient or business location for employee testing in the Houston area after they set up an appointment.  "This summer I become an EMT, training at the Texas EMS Academy in Corpus Christi," says Taft Foley III, co-founder of Texas Mobile Medical Labs. "When I got back to Houston I was asked to take a COVID-19 test, but I was met with a line that wrapped around the entire building and took two hours just to get inside." According to Foley, that spurred him into finding a better way to get results to people quickly.

"I did my research and found a better alternative to increase testing and reduce waiting times," says Taft. "The antigen test works in 15 minutes, which makes them amenable to point-of-care use. That's when I really got the idea of going out to our patients for the test so that they don't have to leave home." The tests are performed with a nasal swab, which then detects a viral protein in an actively infected person, giving accurate and fast results. Antigens are molecules capable of stimulating an immune response. The SARS-CoV-2 that causes COVID-19 has several known antigens including its nucleocapsid phosphoprotein and spike glycoprotein, which are the visible protrusions on its surface. Antigen tests reveal if a person is currently infected with a pathogen such as the SARS-CoV-2 virus. Once the infection is gone, the antigen disappears. Although antigen tests typically have lower sensitivity than a traditional PCR test, that detects the virus through its genetic material, they provide tests rapidly and are relatively cheaper to produce.

"Getting this test to as many people as possible as fast as possible is essential," says Taft. "People need to know whether or not they need to stay home and if they're at risk of spreading the virus to others." The results are sent to patients via text message or email, giving individuals peace of mind quickly if they are not infected and allowing those with COVID-19 to quarantine themselves and those they have exposed. The test cost ranges from $100 to $150 for individuals, according to their website, depending on if testers would like to go to their tent location or take advantage of their mobile lab. While they currently do not accept insurance, most insurance companies will reimburse some or all of the cost of the test. You can reach the Texas Mobile Medical lab at (936) 333-3333 if you have COVID-19 symptoms and would like to schedule an appointment for testing.

Texas Mobile Medical Lab website:

http://www.texasmobilemedicallabs.com/

One of the keys to bringing a viral outbreak under control is rapid detection and diagnosis, which depend on the availability of fast, low-cost, easy-to-use tests that don't require labs or expensive equipment to process them. Scientists at the Broad Institute of MIT and Harvard and collaborators in the United States, Nigeria, and Sierra Leone have now validated such tests for Ebola and Lassa—two of the deadliest and most transmissible human viruses—in settings with limited infrastructure. The work appears in Nature Communications. The diagnostic tests use the CRISPR-based SHERLOCK assay to detect low levels of virus in patient samples and generate either a fluorescent readout or a result on a paper strip. The test can be tailored to detect specific viruses from certain regions, requires only a simple heat block and basic supplies to run, costs less than US$1 per sample, could be used on saliva or urine—eliminating the need for blood draws—and can return results in less than an hour. The tests also use a rapid chemical and heat treatment called HUDSON to inactive the virus in patient samples. HUDSON makes the patient samples safer for clinical staff to handle in a low-tech environment, and eliminates the need to extract a virus's genetic material from the samples before analyzing. The research team was led at Broad by Kayla Barnes, an NIH Fogarty K fellow at the Harvard School of Public Health and Broad Institute, Anna Lachenauer, a medical student at Stanford University School of Medicine, and institute member Pardis Sabeti, a professor at Harvard University and investigator with the Howard Hughes Medical Institute.

To showcase SHERLOCK's field utility, team members led by Christian Happi at Redeemer's University in Nigeria deployed a Lassa-specific assay during a recent Lassa fever outbreak—the first use of SHERLOCK in a low/middle income country. The team also compared the diagnostic against a standard RT-qPCR assay for Lassa. Collaborators at Kenema Government Hospital in Sierra Leone and at the US Army Medical Research Institute of Infectious Diseases benchmarked an Ebola-specific version of the SHERLOCK assay, using samples collected during the 2014-16 outbreak in Sierra Leone and more recent outbreaks in the Democratic Republic of the Congo. The NIH Integrated Research Facility also validated HUDSON's ability to heat-inactivate Ebola virus in their BL4 facilities, further establishing the safety and efficiency of this step. The SHERLOCK assays performed as consistently as, or better than, other diagnostics in these validations—demonstrating the platform's potential for clinical use in the future in resource-limited areas. The team also developed a mobile phone app called HandLens, spearheaded by Andres Colubri, assistant professor in the Bioinformatics and Integrative Biology program at the University of Massachusetts Medical School, that can read and immediately report paper strip SHERLOCK results. The tool can aid in situations where the paper strip gives a faint signal that is challenging for a clinician to interpret. This app can be adapted for use on any smartphone or tablet, according to the researchers, allowing a clear, unbiased diagnostic readout.

Published in Nature Communications (August 17, 2020):

https://doi.org/10.1038/s41467-020-17994-9

The aim of this study is to evaluate if the sweat produced by COVID-19 persons (SARS-CoV-2 PCR positive) has a different odour for trained detection dogs than the sweat produced by non COVID-19 persons. The study was conducted on 3 sites, following the same protocol procedures, and involved a total of 18 dogs. A total of 198 armpits sweat samples were obtained from different hospitals. For each involved dog, the acquisition of the specific odour of COVID-19 sweat samples required from one to four hours, with an amount of positive samples sniffing ranging from four to ten. For this proof of concept, we kept 8 dogs of the initial group (explosive detection dogs and colon cancer detection dogs), who performed a total of 368 trials, and will include the other dogs in our future studies as their adaptation to samples scenting takes more time.

The percentages of success of the dogs to find the positive sample in a line containing several other negative samples or mocks (2 to 6) were 100p100 for 4 dogs, and respectively 83p100, 84p100, 90p100 and 94p100 for the others, all significantly different from the percentage of success that would be obtained by chance alone. We conclude that there is a very high evidence that the armpits sweat odour of COVID-19+ persons is different, and that dogs can detect a person infected by the SARS-CoV-2 virus.

Preprint Available in bioRxiv (June 5, 2020):

https://doi.org/10.1101/2020.06.03.132134

PRNewswire -- SEKISUI Diagnostics, a global medical diagnostics manufacturer, has received EUA clearance for the OSOM Flu SARS-CoV-2 Combo Test for  use in professional and home testing settings.

The OSOM® Flu SARS-CoV-2 Combo Test is a lateral flow immunochromatographic assay intended for in vitro rapid, simultaneous qualitative detection and differentiation of influenza A and influenza B nucleoprotein antigens and SARS-CoV-2 nucleocapsid antigen. As with other OSOM Rapid Tests, it is made in the USA and supported by a highly skilled technical support team of medical technologists/professionals. "The utility of detecting COVID and Flu on one test is now more important than ever having moved into the endemic phase of COVID. The OSOM test is the first antigen, visual, home test to receive EUA status, which allows us to get these diagnostic tools into the hands of healthcare providers and consumers well before the next respiratory season.  This helps minimize the spread of these diseases and allows prescribing appropriate treatments once viruses start circulating.", said Lee Lipski, Sr. VP, Strategy & Business Management.   

SEKISUI Diagnostics is a well-known provider of many rapid diagnostic solutions to the professional and home testing markets through a portfolio of tests under the OSOM® and Acucy® brands. They also supply COVID Ag tests through the HHS/ASPR program (COVIDTests.gov) which delivers tests for free to households across the country. "We first entered the home testing market with our COVID-19 test as we understand these are valuable tools to reduce the spread of respiratory infections and improve the health of all people.  The OSOM Flu SARS-CoV-2 Combo Test takes our offering to the next level with the ability to get two answers with one sample providing fast, actionable results to consumers as well as healthcare professionals.", said Erica Blight, VP, Clinical Research, Customer Care and Marketing.

About SEKISUI Diagnostics:

With over 40 years of experience, SEKISUI Diagnostics' mission is to provide intelligent solutions to enhance life with science and improve the health of all people.  We supply innovative medical diagnostics globally to physicians, hospitals, laboratories and alternate testing locations.   Our product lines include clinical chemistry reagents, point-of-care tests, pre-analytic systems as well as enzymes and specialty biochemicals.    The OSOM® Flu SARS-CoV-2 Combo Test is test is authorized for use at the Point of Care (POC), i.e., in patient care settings operating under a CLIA Certificate of Waiver, Certificate of Compliance, or Certificate of Accreditation and the OSOM® Flu SARS-CoV-2 Combo Home Test is authorized for non-prescription home use with self-collected or adult-collected anterior nares nasal swab samples from individuals aged 14 years or older with signs and symptoms of SARS-CoV-2, influenza A and influenza B. The OSOM Flu SARS CoV-2 Combo Test and the OSOM Flu SARS CoV-2 Combo Home Test are only for in vitro diagnostic use under the Food and Drug Administration's Emergency Use Authorization. This product has not been FDA-cleared or approved.

FDA EUA  letter  (Feb. 29, 2023):

https://www.fda.gov/media/176716/download 

At-home testing is becoming a thing not just for COVID-19, but for seasonal flu and other infections. Here's what you need to know. B efore COVID-19, figuring out whether a sore throat, fever, and runny nose were caused by a cold, flu, or strep wasn’t a top priority. You either powered through, knowing you’d be miserable for a few days but would probably feel better soon or you visited the doctor’s office, urgent care, or emergency room where you might get a test to figure out which virus or bacteria was behind your misery, and maybe a prescription to treat it. But even doctors often don’t order tests, preferring instead to make diagnoses based on symptoms. During the pandemic, however, it became more critical to know who was infected with SARS-CoV-2 so those people could isolate and not spread the virus. At-home test kits became household products, and most people are by now adept at squeezing out a few drops of solution onto a card, sticking a swab up their nose, swirling the swab in the testing liquid, and waiting for a result.

Tests for COVID-19

A number of companies, offer at-home test kits for COVID-19 that people can buy without a prescription. Most of these are rapid antigen tests, which pick up antigens, or substances that the SARS-CoV-2 virus makes. While they are relatively accurate, because it takes some time for levels of these antigens to build up after an infection, these tests are less reliable in the day or so immediately after exposure to the virus. That’s why doctors recommend repeating the test a couple of days apart. Then there are PCR, or molecular, tests, that are closer to the gold standard used in laboratories, and rely on finding the smallest genetic signatures of the virus and amplifying them. Cue Health sells a palm-sized COVID-19 PCR device that people can purchase for $300 that allows for 10 at-home tests and doesn’t require a prescription. The device reads a saliva sample and provides results to a smartphone app in 20 minutes. Other testing companies, such as Labcorp and Everlywell, also sell PCR-based tests for COVID-19, but they are technically collection kits, which means that you have to send a saliva sample into a lab to get results, which can mean critical days will pass before you get results.

Tests for seasonal flu

There is only one at-home test authorized by the FDA for influenza: Lucira, now owned by Pfizer, makes a combined flu and COVID-19 molecular test. The kit uses a PCR-related method of amplifying and reading any viral genes in a sample, providing a result in about 30 minutes. In coming months, eMed, a digital health company that sells test kits and telehealth services, plans to offer that kit, as well another that is currently being reviewed by the U.S. Food and Drug Administration. (The combined kit currently available on eMed’s website only tests for COVID-19 and provides a survey to help telemedicine professionals determine if a user likely has the flu.)

Tests for RSV

There currently aren’t at-home tests for RSV, because typically only infants and the elderly are at risk for severe illness. Doctors’ offices, hospitals, and urgent care centers can perform RSV tests that provide results in about 30 minutes.

The advantages of at-home testing

The currently cumbersome journey from symptoms to treatment rests on people making appointments with their doctors or at an urgent care center and could be contributing to the spread of viruses. Self-testing could reduce some of that risk since people are most infectious while they are waiting to get tested and receive treatment. Ideally, if someone tests themselves at home and finds they are positive for influenza or COVID-19, for example, they don’t necessarily have to physically visit their doctor or go into an urgent care or emergency room, where they could spread the virus to others. Instead, they could video conference with a doctor who could assess their symptoms and at-home test results, then write a prescription for, say, oseltamivir if it’s the flu, or Paxlovid if it’s COVID-19. “If you’re trying to minimize morbidity and mortality, and cut down on transmission, then [at-home] testing is an incredible tool to have,” says Thomas Denny, chief operating officer of the Duke University Human Vaccine Institute....

Elementary students lined up behind a white curtain in the middle of a grand gymnasium at their school in northern California. They stood still as a dog handler walked a yellow Labrador along the other side of the curtain. Hidden from the children’s view, the 2-year-old female pup sniffed each child’s shoes from beneath that curtain barrier. After each sniff, the dog looked back up at the handler. Then the handler brought the dog to the next tiny pair of feet beneath the curtain, and the dog curiously brought her snout close to those toes, then a young girl’s lavender tennis shoes and then another child’s white high-tops. The dog was smelling for what are called volatile organic compounds that are known to be associated with Covid-19 infections. While watching the Covid-sniffing dog in action, Dr. Carol Glaser saw her vision come to life. Months prior, Glaser and her team were implementing the school’s Covid-19 testing program, using antigen nasal swab tests. Around that same time, Glaser heard about reports of dogs being used to screen for Covid-19 infections in sports venues, airports and other public settings. That’s when Glaser had her “aha” moment – incorporating canines into Covid-19 testing programs at schools, nursing homes or other public facilities could help save time, personnel, possibly even costs, and “would be a lot more fun,” she said. “I thought if we had dogs in schools to screen the students it would be so much faster and less burdensome for schools,” said Glaser, assistant deputy director in Central Laboratory Services and medical officer for infectious disease laboratories at the California Department of Public Health. “Remember when an antigen test is done at school, as opposed to home, there’s a whole bunch of rules and regulations that run under that. It’s not as simple as just handing those things out at school and having the kids do them,” said Glaser, who oversaw antigen testing programs at some California public schools. For now, Glaser and her colleagues described in a new study the lessons they learned from the Covid-19 dog screening pilot program that they launched in some California K-12 public schools. In their research, published Monday in the journal JAMA Pediatrics, they wrote that the goal was to use dogs for screening and only use antigen tests on people whom the dogs screened as positive – ultimately reducing the volume of antigen tests performed by about 85%. They wrote that their study supports the “use of dogs for efficient and noninvasive” Covid-19 screening and “could be used for other pathogens.”

Letting the dogs out for screening

The dogs used in the pilot program – two yellow Labradors named Rizzo and Scarlett – trained for a couple of months in a laboratory, sniffing donated socks that were worn by people who either had Covid-19 or didn’t. The dogs alerted their handlers when they detected socks that had traces of the disease – and received a reward of either Cheerios or liver treats. “The one thing we do know for sure is when you’re collecting a sample off of a human being, you want to go where the most scent is produced. That is the head, the pits, the groin and the feet. Given those options, I went with feet,” said Carol Edwards, an author of the study and executive director of the nonprofit Early Alert Canines, which trains medical alert service dogs, including Rizzo and Scarlett. “We collected some socks from people willing to donate socks, and we taught the dogs, by smelling the socks, which ones were the Covid socks and they picked it up very quickly,” Edwards said. “Then we moved into the schools and started sniffing the kids at the ankles.” Last year, from April to May, the dogs visited 27 schools across California to screen for Covid-19 in the real world. They completed more than 3,500 screenings. Rizzo acted as an energized worker, performing tasks with eagerness, Edwards said, while Scarlett tended to have more of a mellow and easygoing personality. The screening process involves people – who voluntarily opted in to participate – standing 6 feet apart while the dogs, led by handlers, sniff each person’s ankles and feet. The dogs are trained to sit as a way of alerting their handlers that they detect a potential Covid-19 infection. To protect each person’s privacy, sometimes the people face away from the dogs and toward a wall or behind a curtain, so that they can’t see the dogs or when a dog sits. If the dog sits in between two people, the handler will verbally ask the dog, “Show me?” And the dog will move its snout to point toward the correct person. “Our dogs can come in, they can screen 100 kids in a half hour, and then only the ones the dog alerts on have to actually do a test,” Edwards said. “There’s no invasive nasal swab unless the dog happens to indicate on you.”

The researchers found that the dogs accurately alerted their handlers to 85 infections and ruled out 3,411 infections, resulting in an overall accuracy of 90%. However, the dogs inaccurately alerted their handlers to infections in 383 instances and missed 18 infections, which means the dogs demonstrated 83% sensitivity and 90% specificity when it came to detecting Covid-19 infections in the study. “Once we stepped into the schools, we saw a drop in their specificity and sensitivity due to the change,” Edwards said, referring to the distractions that children in a school setting can bring. However, Edward said, accuracy improved as the dogs spent more times in schools. In comparison, Covid-19 BinaxNOW antigen tests have been shown in one real-world study to demonstrate 93.3% sensitivity and 99.9% specificity. That study was conducted in San Francisco and published in 2021 in The Journal of Infectious Diseases. “We never said the dogs will replace the antigen. This was a time for us to learn how they compared,” Glaser said. “We will always plan on doing some amount of backup testing, but the idea would be that the actual antigen testing would be a fraction of what it would currently be because of the dogs.” “To run these antigen testing programs at school, it’s taking a lot of school personnel resources, test cards as well as biohazard waste. So, I have no doubt in the long-run once it can be perfected, dogs will be cheaper, but I don’t have a great cost comparison,” she said. This isn’t the first time that dogs’ abilities to detect traces of Covid-19 infections in real-time have been studied in the scientific literature. “What we have learned in this work is that the dogs in general are capable of discriminating samples from individuals testing,” said Dr. Cindy Otto, professor and director of the Penn Vet Working Dog Center at the University of Pennsylvania, who was not involved in the new study. Regarding the new research, Otto said, “On the surface their results are encouraging and with the appropriate selection of dogs, rigorous training and impeccable quality control, there is the potential for dogs to be incorporated in threat monitoring.”

Nursing homes could be next

Now that Glaser and her colleagues have published research about their Covid-19 dog screening pilot program, she is eager to implement the approach in nursing home settings. “Honestly, schools aren’t that interested in testing anymore. The outbreaks just aren’t what they used to be, but what we have done is we’ve transitioned to nursing homes, because there is a tremendous need in nursing homes,” Glaser said, adding that many residents may prefer to undergo screening with a dog than with uncomfortable nasal swabs. “What would you rather have: A swab in your nose or something that just maybe tickles your ankle at most for testing?” In skilled nursing homes, the dogs visit each resident’s room to sniff their feet, calmly smelling for Covid-19 volatile organic compounds as the resident lies in bed or sits in a chair. “Thinking about where dogs would be deployed, I do really think nursing homes and residential care facilities and even schools – if they were ever to have a big outbreak – would be the natural next fit for this,” Glaser said. “We think we’ll probably end up primarily using them in nursing homes,” she said. “But we’re still doing a little bit of both – there was a school that asked us to come back last week.” The pilot program within California public schools also has left Edwards with hope for future opportunities in which canines can help detect disease in humans. “I really do think it’s the tip of the iceberg. This is the door swinging wide open, and now we need to collaborate with those in the science world and figure out where we can take this,” Edwards said. “There’s been a lot of chatter, even in the very beginning of this project, talking about what other diseases they could do. We’ve talked about TB, we’ve talked about flu A and B, possibly for this next flu season, seeing if we can get the dogs to alert on that,” she said, as volatile organic compounds are also produced by people with influenza. “It’s just a matter of being able to figure out how to collect samples, how to train the dogs, and then to be safe and effective around those diseases too.”

Research published in JAMA Pediatrics (April 24, 2023):

https://doi.org/10.1001/jamapediatrics.2023.0489

Rapid Antigen Tests (RAT) have become an invaluable tool for combating the COVID-19 pandemic. However, concerns have been raised regarding the ability of existing RATs to effectively detect emerging SARS-CoV-2 variants. We compared the performance of eight commercially available, emergency use authorized RATs against the Delta and Omicron SARS-CoV-2 variants using individual patient and serially diluted pooled clinical samples. The RATs exhibited lower sensitivity for Omicron samples when using PCR Cycle threshold (CT) value (a proxy for RNA concentration) as the comparator. Interestingly, however, they exhibited similar sensitivity for Omicron and Delta samples when using quantitative antigen concentration as the comparator. We further found that the Omicron samples had lower ratios of antigen to RNA, which offers a potential explanation for the apparent lower sensitivity of RATs for that variant when using CT value as a reference. Our findings underscore the complexity in assessing RAT performance against emerging variants and highlight the need for ongoing evaluation in the face of changing population immunity and virus evolution.

Preprint available in medRxiv (Feb. 10, 2023):

https://doi.org/10.1101/2023.02.09.23285583 

Unlike similar at-home tests, Ellume’s does not require a prescription.  The Food and Drug Administration on Tuesday issued an emergency authorization for the country’s first coronavirus test that can run from start to finish at home without the need for a prescription. People as young as 2 years old are cleared to use the test, which takes just 15 to 20 minutes to deliver a result. Unlike many similar products, which are only supposed to be used by people with symptoms of Covid-19, this test is authorized for people with or without symptoms. The test, developed by the Australian company Ellume, detects bits of coronavirus proteins called antigens. It’s slightly less accurate than gold standard laboratory tests designed to look for coronavirus genetic material with a technique called polymerase chain reaction, or P.C.R. But in a clinical study of nearly 200 people, Ellume’s product was able to detect 95 percent of the coronavirus infections found by P.C.R., regardless of whether the infected people felt sick. It also correctly identified 97 percent of the people who received negative laboratory test results.

Viral levels in people infected with SARS-CoV-2 in a specific town or city could be used to assess whether the epidemic there has passed its peak. A common test for SARS-CoV-2 allows doctors to measure an infected person’s ‘viral load’, an indicator of the amount of virus in their body. James Hay at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, and his colleagues, used modelling to show that the viral loads of a population correlate with the rate of viral spread in that population (J. A. Hay et al. Preprint at medRxiv https://doi.org/ghfm73; 2020).

Early in an epidemic, the average infected person has been recently exposed to the virus and therefore has a high viral load. Later in the epidemic, the average infected person has had the virus for longer and has a low viral load. As a result, a snapshot of the viral-load distribution in a random sample of a population can reveal whether cases in that population are on the rise or are declining, the researchers say. They add that their method is less susceptible to biases from changing COVID-testing practices than simply counting daily cases. The findings have not yet been peer reviewed.

CRISPR-based approach is much faster than current diagnostics, but does have some limitation. CRISPR diagnostics are just one way researchers are trying to speed coronavirus testing. The new test is the fastest CRISPR-based diagnostic yet. In May, for example, two teams reported creating CRISPR-based coronavirus tests that could detect the virus in about an hour, much faster than the 24 hours needed for conventional coronavirus diagnostic tests.  CRISPR tests work by identifying a sequence of RNA—about 20 RNA bases long—that is unique to SARS-CoV-2. They do so by creating a “guide” RNA that is complementary to the target RNA sequence and, thus, will bind to it in solution. When the guide binds to its target, the CRISPR tool’s Cas13 “scissors” enzyme turns on and cuts apart any nearby single-stranded RNA. These cuts release a separately introduced fluorescent particle in the test solution. When the sample is then hit with a burst of laser light, the released fluorescent particles light up, signaling the presence of the virus. These initial CRISPR tests, however, required researchers to first amplify any potential viral RNA before running it through the diagnostic to increase their odds of spotting a signal. That added complexity, cost, and time, and put a strain on scarce chemical reagents.

Now, researchers led by Jennifer Doudna, who won a share of this year’s Nobel Prize in Chemistry yesterday for her co-discovery of CRISPR, report creating a novel CRISPR diagnostic that doesn’t amplify coronavirus RNA. Instead, Doudna and her colleagues spent months testing hundreds of guide RNAs to find multiple guides that work in tandem to increase the sensitivity of the test. 

In a new preprint, the researchers report that with a single guide RNA, they could detect as few as 100,000 viruses per microliter of solution. And if they add a second guide RNA, they can detect as few as 100 viruses per microliter.  That’s still not as good as the conventional coronavirus diagnostic setup, which uses expensive lab-based machines to track the virus down to one virus per microliter, says Melanie Ott, a virologist at UC San Francisco who helped lead the project with Doudna. However, she says, the new setup was able to accurately identify a batch of five positive clinical samples with perfect accuracy in just 5 minutes per test, whereas the standard test can take 1 day or more to return results.

Illumina has secured an emergency use authorisation (EUA) from the US Food and Drug Administration (FDA) for its sequencing-based Covid-19 diagnostic test. Illumina COVIDSeq test is a high-throughput, sequencing-based and in vitro diagnostic (IVD) workflow test that facilitates the detection of SARS-CoV-2. The sequencing-based diagnostic test, which uses upper respiratory specimens such as nasopharyngeal or oropharyngeal swab, offers sample receipt to result in 24 hours using the NovaSeq 6000 sequencing system. The differentiated diagnostic design is comprised of 98 amplicons, which target the full SARS-CoV-2 genome, enabling to create precise detection and high sensitivity.

Illumina is currently offering COVIDSeq test to a limited number of early access sites, and plans to increase the supply by summer. The workflow holds the capacity to accommodate up to 3,072 samples per NovaSeq run through leveraging the S4 flow cell. It is comprised of steps for viral RNA extraction, RNA-to-CDNA conversion, PCR, library preparation, sequencing and report generation. 

FDA Letter of Approval:

https://www.fda.gov/media/79226/download