The Nose Knows: Dogs Are Being Trained to Detect the Coronavirus
Security workers walk with detection dogs in an airport terminal.
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."
Researchers Are Discovering How to Predict – and Maybe Treat — Pregnancy Complications Early On.
Katie Love cradles her newborn daughter, born after a bout with preeclampsia.
Katie Love wishes there was some way she could have been prepared. But there was no way to know, early in 2020, that her pregnancy would lead to terrifyingly high blood pressure and multiple hospital visits, ending in induced labor and a 56-hour-long, “nightmare” delivery at 37 weeks. Love, a social media strategist in Pittsburgh, had preeclampsia, a poorly understood and potentially deadly pregnancy complication that affects 1 in 25 pregnant women in the United States. But there was no blood test, no easy diagnostic marker to warn Love that this might happen. Even on her first visit to the emergency room, with sky-high blood pressure, doctors could not be certain preeclampsia was the cause.
In fact, the primary but imperfect indicators for preeclampsia — high blood pressure and protein in the urine — haven’t changed in decades. The Preeclampsia Foundation calls a simple, rapid test to predict or diagnose the condition “a key component needed in the fight.”
Another common pregnancy complication is preterm birth, which affects 1 in 10 U.S. pregnancies, but there are few options to predict that might happen, either.
“The best tool that obstetricians have at the moment is still a tape measure and a blood pressure cuff to diagnose whatever’s happening in your pregnancy,” says Fiona Kaper, a vice president at the DNA-sequencing company Illumina in San Diego.
The hunt for such specific biomarkers is now taking off, at Illumina and elsewhere, as scientists probe maternal blood for signs that could herald pregnancy problems. These same molecules offer clues that might lead to more specific treatments. So far, it’s clear that many complications start with the placenta, the temporary organ that transfers nutrients, oxygen and waste between mother and fetus, and that these problems often start well before symptoms arise. Researchers are using the latest stem-cell technology to better understand the causes of complications and test treatments.
Pressing Need
Obstetricians aren’t flying completely blind; medical history can point to high or low risk for pregnancy complications. But ultimately, “everybody who’s pregnant is at risk for preeclampsia,” says Sarosh Rana, chief of maternal-fetal medicine at University of Chicago Medicine and an advisor to the Preeclampsia Foundation. And the symptoms of the condition include problems like headache and swollen feet that overlap with those of pregnancy in general, complicating diagnoses.
The “holy grail" would be early, first-trimester biomarkers. If obstetricians and expecting parents could know, in the first few months of pregnancy, that preeclampsia is a risk, a pregnant woman could monitor her blood pressure at home and take-low dose aspirin that might stave it off.
There are a couple more direct tests physicians can turn to, but these are imperfect. For preterm labor, fetal fibronectin makes up a sort of glue that keeps the amniotic sac, which cushions the unborn baby, attached to the uterus. If it’s not present near a woman’s cervix, that’s a good indicator that she’s not in labor, and can be safely sent home, says Lauren Demosthenes, an obstetrician and senior medical director of the digital health company Babyscripts in Washington, D.C. But if fibronectin appears, it might or might not indicate preterm labor.
“What we want is a test that gives us a positive predictive [signal],” says Demosthenes. “I want to know, if I get it, is it really going to predict preterm birth, or is it just going to make us worry more and order more tests?” In fact, the fetal fibronectin test hasn’t been shown to improve pregnancy outcomes, and Demosthenes says it’s fallen out of favor in many clinics.
Similarly, there’s a blood test, based on the ratio of the amounts of two different proteins, that can rule out preeclampsia but not confirm it’s happening. It’s approved in many countries, though not the U.S.; studies are still ongoing. A positive test, which means “maybe preeclampsia,” still leaves doctors and parents-to-be facing excruciating decisions: If the mother’s life is in danger, delivering the baby can save her, but even a few more days in the uterus can promote the baby’s health. In Ireland, where the test is available, it’s not getting much use, says Patricia Maguire, director of the University College Dublin Institute for Discovery.
Maguire has identified proteins released by platelets that indicate pregnancy — the “most expensive pregnancy test in the world,” she jokes. She is now testing those markers in women with suspected preeclampsia.
The “holy grail,” says Maguire, would be early, first-trimester biomarkers. If obstetricians and expecting parents could know, in the first few months of pregnancy, that preeclampsia is a risk, a pregnant woman could monitor her blood pressure at home and take-low dose aspirin that might stave it off. Similarly, if a quick blood test indicated that preterm labor could happen, doctors could take further steps such as measuring the cervix and prescribing progesterone if it’s on the short side.
Biomarkers in Blood
It was fatherhood that drew Stephen Quake, a biophysicist at Stanford University in California, to the study of pregnancy biomarkers. His wife, pregnant with their first child in 2001, had a test called amniocentesis. That involves extracting a sample from within the uterus, using a 3–8-inch-long needle, for genetic testing. The test can identify genetic differences, such as Down syndrome, but also carries risks including miscarriage or infection. In this case, mom and baby were fine (Quake’s daughter is now a college student), but he found the diagnostic danger unacceptable.
Seeking a less invasive test, Quake in 2008 reported that there’s enough fetal DNA in the maternal bloodstream to diagnose Down syndrome and other genetic conditions. “Use of amniocentesis has plunged,” he says.
Then, recalling that his daughter was born three and a half weeks before her due date — and that Quake’s own mom claims he was a month late, which makes him think the due date must have been off — he started researching markers that could accurately assess a fetus’ age and predict the timing of labor. In this case, Quake was interested in RNA, not DNA, because it’s a signal of which genes the fetus’, placenta’s, and mother’s tissues are using to create proteins. Specifically, these are RNAs that have exited the cells that made them. Tissues can use such free RNAs as messages, wrapping them in membranous envelopes to travel the bloodstream to other body parts. Dying cells also release fragments containing RNAs. “A lot of information is in there,” says Kaper.
In a small study of 31 healthy pregnant women, published in 2018, Quake and collaborators discovered nine RNAs that could predict gestational age, which indicates due date, just as well as ultrasound. With another set of 38 women, including 13 who delivered early, the researchers discovered seven RNAs that predicted preterm labor up to two months in advance.
Quake notes that an RNA-based blood test is cheaper and more portable than ultrasound, so it might be useful in the developing world. A company he cofounded, Mirvie, Inc., is now analyzing RNA’s predictive value further, in thousands of diverse women. CEO and cofounder Maneesh Jain says that since preterm labor is so poorly understood, they’re sequencing RNAs that represent about 20,000 genes — essentially all the genes humans have — to find the very best biomarkers. “We don’t know enough about this field to guess what it might be,” he says. “We feel we’ve got to cast the net wide.”
Quake, and Mirvie, are now working on biomarkers for preeclampsia. In a recent preprint study, not yet reviewed by other experts, Quake’s Stanford team reported 18 RNAs that, measured before 16 weeks, correctly predicted preeclampsia 56–100% of the time.
Other researchers are taking a similar tack. Kaper’s team at Illumina was able to classify preeclampsia from bloodstream RNAs with 85 to 89% accuracy, though they didn’t attempt to predict it. And Louise Laurent, a maternal-fetal medicine specialist and researcher at the University of California, San Diego (UCSD), has defined several pairs of microRNAs — pint-sized RNAs that regulate other ones — in second-trimester blood samples that predict preeclampsia later on.
Placentas in a Dish
The RNAs that show up in these studies often come from genes used by the placenta. But they’re only signals that something’s wrong, not necessarily the root cause. “There still is not much known about what really causes major complications of pregnancy,” says Laurent.
The challenge is that placental problems likely occur early on, as the organ forms in the first trimester. For example, if the placenta did a poor job of building blood vessels through the uterine lining, it might cause preeclampsia later as the growing fetus tries to access more and more blood through insufficient vessels, leading to high blood pressure in the mother. “Everyone has kind of suspected that that is probably what goes wrong,” says Mana Parast, a pathologist and researcher at UCSD.
To see how a placenta first faltered, “you want to go back in time,” says Parast. It’s only recently become possible to do something akin to that: She and Laurent take cells from the umbilical cord (which is a genetic match for the placenta) at the end of pregnancy, and turn them into stem cells, which can become any kind of cell. They then nudge those stem cells to make new placenta cells in lab dishes. But when the researchers start with cells from an umbilical cord after preeclampsia, they find the stem cells struggle to even form proper placenta cells, or they develop abnormally. So yes, something seems to go wrong right at the beginning. Now, the team plans to use these cell cultures to study the microRNAs that indicate preeclampsia risk, and to look for medications that might reverse the problems, Parast says.
Biomarkers could lead to treatments. For example, one of the proteins that commercial preeclampsia diagnostic kits test for is called soluble Flt-1. It’s a sort of anti-growth factor, explains Rana, that can cause problems with blood vessels and thus high blood pressure. Getting rid of the extra Flt-1, then, might alleviate symptoms and keep the mother safe, giving the baby more time to develop. Indeed, a small trial that filtered this protein from the blood did lower blood pressure, allowing participants to keep their babies inside for a couple of weeks longer, researchers reported in 2011.
For pregnant women like Love, even advance warning would have been beneficial. Laurent and others envision a first-trimester blood test that would use different kinds of biomolecules — RNAs, proteins, whatever works best — to indicate whether a pregnancy is at low, medium, or high risk for common complications.
“I prefer to be prepared,” says Love, now the mother of a healthy little girl. “I just wouldn’t have been so thrown off by the whole thing.”
Dec. 17th Event: The Latest on Omicron, Boosters, and Immunity
The Omicron variant poses new uncertainty for the vaccines, which four leading experts will address during our virtual event on December 17th, 2021.
This virtual event will convene leading scientific and medical experts to discuss the most pressing questions around the new Omicron variant, including what we know so far about its ability to evade COVID-19 vaccines, the role of boosters in eliciting heightened immunity, and the science behind variants and vaccines. A public Q&A will follow the expert discussion.
EVENT INFORMATION:
Date: Friday Dec 17, 2021
2:00pm - 3:30pm EST
Dr. Céline Gounder, MD, ScM, is the CEO/President/Founder of Just Human Productions, a non-profit multimedia organization. She is also the host and producer of American Diagnosis, a podcast on health and social justice, and Epidemic, a podcast about infectious disease epidemics and pandemics. She served on the Biden-Harris Transition COVID-19 Advisory Board.
Dr. Theodora Hatziioannou, Ph.D., is a Research Associate Professor in the Laboratory of Retrovirology at The Rockefeller University. Her research includes identifying plasma samples from recovered COVID-19 patients that contain antibodies capable of neutralizing the SARS-CoV-2 coronavirus.
Dr. Onyema Ogbuagu, MBBCh, is an Associate Professor at Yale School of Medicine and an infectious disease specialist who treats COVID-19 patients and leads Yale’s clinical studies around COVID-19. He ran Yale’s trial of the Pfizer/BioNTech vaccine.
Dr. Eric Topol, M.D., is a cardiologist, scientist, professor of molecular medicine, and the director and founder of Scripps Research Translational Institute. He has led clinical trials in over 40 countries with over 200,000 patients and pioneered the development of many routinely used medications.
This event is the fourth of a four-part series co-hosted by Leaps.org, the Aspen Institute Science & Society Program, and the Sabin–Aspen Vaccine Science & Policy Group, with generous support from the Gordon and Betty Moore Foundation and the Howard Hughes Medical Institute.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.