The Nose Knows: Dogs Are Being Trained to Detect the Coronavirus
Asher is eccentric and inquisitive. He loves an audience, likes keeping busy, and howls to be let through doors. He is a six-year-old working Cocker Spaniel, who, with five other furry colleagues, has now been trained to sniff body odor samples from humans to detect COVID-19 infections.
As the Delta variant and other new versions of the SARS-CoV-2 virus emerge, public health agencies are once again recommending masking while employers contemplate mandatory vaccination. While PCR tests remain the "gold standard" of COVID-19 tests, they can take hours to flag infections. To accelerate the process, scientists are turning to a new testing tool: sniffer dogs.
At the London School of Hygiene and Tropical Medicine (LSHTM), researchers deployed Asher and five other trained dogs to test sock samples from 200 asymptomatic, infected individuals and 200 healthy individuals. In May, they published the findings of the yearlong study in a preprint, concluding that dogs could identify COVID-19 infections with a high degree of accuracy – they could correctly identify a COVID-positive sample up to 94% of the time and a negative sample up to 92% of the time. The paper has yet to be peer-reviewed.
"Dogs can screen lots of people very quickly – 300 people per dog per hour. This means they could be used in places like airports or public venues like stadiums and maybe even workplaces," says James Logan, who heads the Department of Disease Control at LSHTM, adding that canines can also detect variants of SARS-CoV-2. "We included samples from two variants and the dogs could still detect them."
Detection dogs have been one of the most reliable biosensors for identifying the odor of human disease. According to Gemma Butlin, a spokesperson of Medical Detection Dogs, the UK-based charity that trained canines for the LSHTM study, the olfactory capabilities of dogs have been deployed to detect malaria, Parkinson's disease, different types of cancers, as well as pseudomonas, a type of bacteria known to cause infections in blood, lungs, eyes, and other parts of the human body.
COVID-19 has a distinctive smell — a result of chemicals known as volatile organic compounds released by infected body cells, which give off an odor "fingerprint."
"It's estimated that the percentage of a dog's brain devoted to analyzing odors is 40 times larger than that of a human," says Butlin. "Humans have around 5 million scent receptors dedicated to smell. Dogs have 350 million and can detect odors at parts per trillion. To put this into context, a dog can detect a teaspoon of sugar in a million gallons of water: two Olympic-sized pools full."
According to LSHTM scientists, COVID-19 has a distinctive smell — a result of chemicals known as volatile organic compounds released by infected body cells, which give off an odor "fingerprint." Other studies, too, have revealed that the SARS-CoV-2 virus has a distinct olfactory signature, detectable in the urine, saliva, and sweat of infected individuals. Humans can't smell the disease in these fluids, but dogs can.
"Our research shows that the smell associated with COVID-19 is at least partly due to small and volatile chemicals that are produced by the virus growing in the body or the immune response to the virus or both," said Steve Lindsay, a public health entomologist at Durham University, whose team collaborated with LSHTM for the study. He added, "There is also a further possibility that dogs can actually smell the virus, which is incredible given how small viruses are."
In April this year, researchers from the University of Pennsylvania and collaborators published a similar study in the scientific journal PLOS One, revealing that detection dogs could successfully discriminate between urine samples of infected and uninfected individuals. The accuracy rate of canines in this study was 96%. Similarly, last December, French scientists found that dogs were 76-100% effective at identifying individuals with COVID-19 when presented with sweat samples.
Grandjean Dominique, a professor at France's National Veterinary School of Alfort, who led the French study, said that the researchers used two types of dogs — search and rescue dogs, as they can sniff sweat, and explosive detection dogs, because they're often used at airports to find bomb ingredients. Dogs may very well be as good as PCR tests, said Dominique, but the goal, he added, is not to replace these tests with canines.
In France, the government gave the green light to train hundreds of disease detection dogs and deploy them in airports. "They will act as mass pre-test, and only people who are positive will undergo a PCR test to check their level of infection and the kind of variant," says Dominique. He thinks the dogs will be able to decrease the amount of PCR testing and potentially save money.
Since the accuracy rate for bio-detection dogs is fairly high, scientists think they could prove to be a quick diagnosis and mass screening tool, especially at ports, airports, train stations, stadiums, and public gatherings. Countries like Finland, Thailand, UAE, Italy, Chile, India, Australia, Pakistan, Saudi Arabia, Switzerland, and Mexico are already training and deploying canines for COVID-19 detection. The dogs are trained to sniff the area around a person, and if they find the odor of COVID-19 they will sit or stand back from an individual as a signal that they've identified an infection.
While bio-detection dogs seem promising for cheap, large-volume screening, many of the studies that have been performed to date have been small and in controlled environments. The big question is whether this approach work on people in crowded airports, not just samples of shirts and socks in a lab.
"The next step is 'real world' testing where they [canines] are placed in airports to screen people and see how they perform," says Anna Durbin, professor of international health at the John Hopkins Bloomberg School of Public Health. "Testing in real airports with lots of passengers and competing scents will need to be done."
According to Butlin of Medical Detection Dogs, scalability could be a challenge. However, scientists don't intend to have a dog in every waiting room, detecting COVID-19 or other diseases, she said.
"Dogs are the most reliable bio sensors on the planet and they have proven time and time again that they can detect diseases as accurately, if not more so, than current technological diagnostics," said Butlin. "We are learning from them all the time and what their noses know will one day enable the creation an 'E-nose' that does the same job – imagine a day when your mobile phone can tell you that you are unwell."
This episode is about a health metric you may not have heard of before: heart rate variability, or HRV. This refers to the small changes in the length of time between each of your heart beats.
Scientists have known about and studied HRV for a long time. In recent years, though, new monitors have come to market that can measure HRV accurately whenever you want.
Five months ago, I got interested in HRV as a more scientific approach to finding the lifestyle changes that work best for me as an individual. It's at the convergence of some important trends in health right now, such as health tech, precision health and the holistic approach in systems biology, which recognizes how interactions among different parts of the body are key to health.
But HRV is just one of many numbers worth paying attention to. For this episode of Making Sense of Science, I spoke with psychologist Dr. Leah Lagos; Dr. Jessilyn Dunn, assistant professor in biomedical engineering at Duke; and Jason Moore, the CEO of Spren and an app called Elite HRV. We talked about what HRV is, research on its benefits, how to measure it, whether it can be used to make improvements in health, and what researchers still need to learn about HRV.
*Talk to your doctor before trying anything discussed in this episode related to HRV and lifestyle changes to raise it.
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Show notes
Spren - https://www.spren.com/
Elite HRV - https://elitehrv.com/
Jason Moore's Twitter - https://twitter.com/jasonmooreme?lang=en
Dr. Jessilyn Dunn's Twitter - https://twitter.com/drjessilyn?lang=en
Dr. Dunn's study on HRV, flu and common cold - https://jamanetwork.com/journals/jamanetworkopen/f...
Dr. Leah Lagos - https://drleahlagos.com/
Dr. Lagos on Star Talk - https://www.youtube.com/watch?v=jC2Q10SonV8
Research on HRV and intermittent fasting - https://pubmed.ncbi.nlm.nih.gov/33859841/
Research on HRV and Mediterranean diet - https://medicalxpress.com/news/2010-06-twin-medite...:~:text=Using%20data%20from%20the%20Emory,eating%20a%20Western%2Dtype%20diet
Devices for HRV biofeedback - https://elitehrv.com/heart-variability-monitors-an...
Benefits of HRV biofeedback - https://pubmed.ncbi.nlm.nih.gov/32385728/
HRV and cognitive performance - https://www.frontiersin.org/articles/10.3389/fnins...
HRV and emotional regulation - https://pubmed.ncbi.nlm.nih.gov/36030986/
Fortune article on HRV - https://fortune.com/well/2022/12/26/heart-rate-var...
Ever since he was a baby, Sharon Wong’s son Brandon suffered from rashes, prolonged respiratory issues and vomiting. In 2006, as a young child, he was diagnosed with a severe peanut allergy.
"My son had a history of reacting to traces of peanuts in the air or in food,” says Wong, a food allergy advocate who runs a blog focusing on nut free recipes, cooking techniques and food allergy awareness. “Any participation in school activities, social events, or travel with his peanut allergy required a lot of preparation.”
Peanut allergies affect around a million children in the U.S. Most never outgrow the condition. The problem occurs when the immune system mistakenly views the proteins in peanuts as a threat and releases chemicals to counteract it. This can lead to digestive problems, hives and shortness of breath. For some, like Wong’s son, even exposure to trace amounts of peanuts could be life threatening. They go into anaphylactic shock and need to take a shot of adrenaline as soon as possible.
Typically, people with peanut allergies try to completely avoid them and carry an adrenaline autoinjector like an EpiPen in case of emergencies. This constant vigilance is very stressful, particularly for parents with young children.
“The search for a peanut allergy ‘cure’ has been a vigorous one,” says Claudia Gray, a pediatrician and allergist at Vincent Pallotti Hospital in Cape Town, South Africa. The closest thing to a solution so far, she says, is the process of desensitization, which exposes the patient to gradually increasing doses of peanut allergen to build up a tolerance. The most common type of desensitization is oral immunotherapy, where patients ingest small quantities of peanut powder. It has been effective but there is a risk of anaphylaxis since it involves swallowing the allergen.
"By the end of the trial, my son tolerated approximately 1.5 peanuts," Sharon Wong says.
DBV Technologies, a company based in Montrouge, France has created a skin patch to address this problem. The Viaskin Patch contains a much lower amount of peanut allergen than oral immunotherapy and delivers it through the skin to slowly increase tolerance. This decreases the risk of anaphylaxis.
Wong heard about the peanut patch and wanted her son to take part in an early phase 2 trial for 4-to-11-year-olds.
“We felt that participating in DBV’s peanut patch trial would give him the best chance at desensitization or at least increase his tolerance from a speck of peanut to a peanut,” Wong says. “The daily routine was quite simple, remove the old patch and then apply a new one. By the end of the trial, he tolerated approximately 1.5 peanuts.”
How it works
For DBV Technologies, it all began when pediatric gastroenterologist Pierre-Henri Benhamou teamed up with fellow professor of gastroenterology Christopher Dupont and his brother, engineer Bertrand Dupont. Together they created a more effective skin patch to detect when babies have allergies to cow's milk. Then they realized that the patch could actually be used to treat allergies by promoting tolerance. They decided to focus on peanut allergies first as the more dangerous.
The Viaskin patch utilizes the fact that the skin can promote tolerance to external stimuli. The skin is the body’s first defense. Controlling the extent of the immune response is crucial for the skin. So it has defense mechanisms against external stimuli and can promote tolerance.
The patch consists of an adhesive foam ring with a plastic film on top. A small amount of peanut protein is placed in the center. The adhesive ring is attached to the back of the patient's body. The peanut protein sits above the skin but does not directly touch it. As the patient sweats, water droplets on the inside of the film dissolve the peanut protein, which is then absorbed into the skin.
The peanut protein is then captured by skin cells called Langerhans cells. They play an important role in getting the immune system to tolerate certain external stimuli. Langerhans cells take the peanut protein to lymph nodes which activate T regulatory cells. T regulatory cells suppress the allergic response.
A different patch is applied to the skin every day to increase tolerance. It’s both easy to use and convenient.
“The DBV approach uses much smaller amounts than oral immunotherapy and works through the skin significantly reducing the risk of allergic reactions,” says Edwin H. Kim, the division chief of Pediatric Allergy and Immunology at the University of North Carolina, U.S., and one of the principal investigators of Viaskin’s clinical trials. “By not going through the mouth, the patch also avoids the taste and texture issues. Finally, the ability to apply a patch and immediately go about your day may be very attractive to very busy patients and families.”
Brandon Wong displaying origami figures he folded at an Origami Convention in 2022
Sharon Wong
Clinical trials
Results from DBV's phase 3 trial in children ages 1 to 3 show its potential. For a positive result, patients who could not tolerate 10 milligrams or less of peanut protein had to be able to manage 300 mg or more after 12 months. Toddlers who could already tolerate more than 10 mg needed to be able to manage 1000 mg or more. In the end, 67 percent of subjects using the Viaskin patch met the target as compared to 33 percent of patients taking the placebo dose.
“The Viaskin peanut patch has been studied in several clinical trials to date with promising results,” says Suzanne M. Barshow, assistant professor of medicine in allergy and asthma research at Stanford University School of Medicine in the U.S. “The data shows that it is safe and well-tolerated. Compared to oral immunotherapy, treatment with the patch results in fewer side effects but appears to be less effective in achieving desensitization.”
The primary reason the patch is less potent is that oral immunotherapy uses a larger amount of the allergen. Additionally, absorption of the peanut protein into the skin could be erratic.
Gray also highlights that there is some tradeoff between risk and efficacy.
“The peanut patch is an exciting advance but not as effective as the oral route,” Gray says. “For those patients who are very sensitive to orally ingested peanut in oral immunotherapy or have an aversion to oral peanut, it has a use. So, essentially, the form of immunotherapy will have to be tailored to each patient.” Having different forms such as the Viaskin patch which is applied to the skin or pills that patients can swallow or dissolve under the tongue is helpful.
The hope is that the patch’s efficacy will increase over time. The team is currently running a follow-up trial, where the same patients continue using the patch.
“It is a very important study to show whether the benefit achieved after 12 months on the patch stays stable or hopefully continues to grow with longer duration,” says Kim, who is an investigator in this follow-up trial.
"My son now attends university in Massachusetts, lives on-campus, and eats dorm food. He has so much more freedom," Wong says.
The team is further ahead in the phase 3 follow-up trial for 4-to-11-year-olds. The initial phase 3 trial was not as successful as the trial for kids between one and three. The patch enabled patients to tolerate more peanuts but there was not a significant enough difference compared to the placebo group to be definitive. The follow-up trial showed greater potency. It suggests that the longer patients are on the patch, the stronger its effects.
They’re also testing if making the patch bigger, changing the shape and extending the minimum time it’s worn can improve its benefits in a trial for a new group of 4-to-11 year-olds.
The future
DBV Technologies is using the skin patch to treat cow’s milk allergies in children ages 1 to 17. They’re currently in phase 2 trials.
As for the peanut allergy trials in toddlers, the hope is to see more efficacy soon.
For Wong’s son who took part in the earlier phase 2 trial for 4-to-11-year-olds, the patch has transformed his life.
“My son continues to maintain his peanut tolerance and is not affected by peanut dust in the air or cross-contact,” Wong says. ”He attends university in Massachusetts, lives on-campus, and eats dorm food. He still carries an EpiPen but has so much more freedom than before his clinical trial. We will always be grateful.”