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."
Could a tiny fern change the world — again?
More than 50 million years ago, the Arctic Ocean was the opposite of a frigid wasteland. It was a gigantic lake surrounded by lush greenery brimming with flora and fauna, thanks to the humidity and warm temperatures. Giant tortoises, alligators, rhinoceros-like animals, primates, and tapirs roamed through nearby forests in the Arctic.
This greenhouse utopia abruptly changed in the early Eocene period, when the Arctic Ocean became landlocked. A channel that connected the Arctic to the greater oceans got blocked. This provided a tiny fern called Azolla the perfect opportunity to colonize the layer of freshwater that formed on the surface of the Arctic Ocean. The floating plants rapidly covered the water body in thick layers that resembled green blankets.
Gradually, Azolla colonies migrated to every continent with the help of repeated flooding events. For around a million years, they captured more than 80 percent of atmospheric carbon dioxide that got buried at the bottom of the Arctic Ocean as billions of Azolla plants perished.
This “Arctic Azolla event” had devastating impacts on marine life. To date, scientists are trying to figure out how it ended. But they documented that the extraordinary event cooled down the Arctic by at least 40 degrees Fahrenheit — effectively freezing the poles and triggering several cycles of ice ages. “This carbon dioxide sequestration changed the climate from greenhouse to white house,” says Jonathan Bujak, a paleontologist who has researched the Arctic through expeditions since 1973.
Some farmers and scientists, such as Bujak, are looking to this ancient fern, which manipulated the Earth’s climate around 49 million years ago with its insatiable appetite for carbon dioxide, as a potential solution to our modern-day agricultural and environmental challenges. “There is no other plant like Azolla in the world,” says Bujak.
Decoding the Azolla plant
Azolla lives in symbiosis with a cyanobacterium called Anabaena that made the plant’s leaf cavities its permanent home at an early stage in Earth's history. This close relationship with Anabaena enables Azolla to accomplish a feat that is impossible for most plants: directly splitting dinitrogen molecules that make up 78 percent of the Earth’s atmosphere.
A dinitrogen molecule consists of two nitrogen atoms tightly locked together in one of the strongest bonds in nature. The semi-aquatic fern’s ability to split nitrogen, called nitrogen-fixing, made it a highly revered plant in East Asia. Rice farmers used Azolla as a biofertilizer since the 11th century in Vietnam and China.
For decades, scientists have attempted to decode Azolla’s evolution. Cell biologist Francisco Carrapico, who worked at the University of Lisbon, has analyzed this distinctive symbiosis since the 1980s. To his amazement, in 1991, he found that bacteria are the third partner of the Azolla-Anabaena symbiosis.
“Azolla and Anabaena cannot survive without each other. They have co-evolved for 80 million years, continuously exchanging their genetic material with each other,” says Bujak, co-author of The Azolla Story, which he published with his daughter, Alexandra Bujak, an environmental scientist. Three different levels of nitrogen fixation take place within the plant, as Anabaena draws down as much as 2,200 pounds of atmospheric nitrogen per acre annually.
“Using Azolla to mitigate climate change might sound a bit too simple. But that is not the case,” Bujak says. “At a microscopic level, extremely complicated biochemical reactions are constantly occurring inside the plant’s cells that machines or technology cannot replicate yet.”
In 2018, researchers based in the U.S. managed to sequence Azolla’s complete genome — which is four times larger than the human genome — through a crowdfunded study, further increasing our understanding of this plant. “Azolla is a superorganism that works efficiently as a natural biotechnology system that makes it capable of doubling in size within three to five days,” says Carrapico.
Making Azolla mainstream again in agriculture
While scientific groups in the Global North have been working towards unraveling the tiny fern’s inner workings, communities in the Global South are busy devising creative ways to return to their traditional agricultural roots by tapping into Azolla’s full potential.
Pham Gia Minh, an entrepreneur living in Hanoi, Vietnam, is one such citizen scientist who believes that Azolla could be a climate savior. More than two decades after working in finance and business development, Minh is now focusing on continuing his grandfather’s legacy, an agricultural scientist who conducted Azolla research until the 1950s. “Azolla is our family’s heritage,” says Minh.
Pham Gia Minh, an entrepreneur and citizen scientist in Hanoi, Vietnam, believes that Azolla could be a climate savior
Pham Gia Minh
Since the advent of chemical fertilizers in the early 1900s, farmers in Asia abandoned Azolla to save on time and labor costs. But rice farmers in the country went back to cultivating Azolla during the Vietnam War after chemical trade embargoes made chemical fertilizers far too expensive and inaccessible.
By 1973, Azolla cultivation in rice paddy fields was established on half a million hectares in Vietnam. By injecting nitrogen into the soil, Azolla improves soil fertility and also increases rice yields by at least 27 percent compared to urea. The plants can also reduce a farm’s methane emissions by 40 percent.
“Unfortunately, after 1985, chemical fertilizers became cheap and widely available in Vietnam again. So, farmers stopped growing Azolla because of the time-consuming and labor-intensive cultivation process,” says Minh.
Minh has invested in a rural farm where he is proving that modern technology can make the process less burdensome. He uses a pump and drying equipment for harvesting Azolla in a small pond, and he deploys a drone for spraying insecticides and fertilizers on the pond at regular intervals.
As Azolla lacks phosphorus, farmers in developing countries still find it challenging to let go of chemical fertilizers completely. Still, Minh and Bujak say that farmers can use Azolla instead of chemical fertilizers after mixing it with dung.
In the last few years, the fern’s popularity has been growing in other developing countries like India, Palestine, Indonesia, the Philippines, and Bangladesh, where local governments and citizens are trying to re-introduce Azolla integrated farming by growing the ferns in small ponds.
Replacing soybeans with Azolla
In Ecuador, Mariano Montano Armijos, a former chemical engineer, has worked with Azolla for more than 20 years. Since 2008, he has shared resources and information for growing Azolla with 3,000 farmers in Ecuador. The farmers use the harvested plants as a bio-fertilizer and feed for livestock.
“The farmers do not use urea anymore,” says Armijos. “This goes against the conventional agricultural practices of using huge amounts of synthetic nitrogen on a hectare of rice or corn fields.”
He insists that Azolla’s greatest strength is that it is a rich source of proteins, making it highly nutritious for human beings as well. After growing Azolla on a small scale in ponds, Armijos and his business partner, Ivan Noboa, are now building a facility for cultivating the ferns as a superfood on an industrial scale.
According to Armijos, one hectare of Azolla in Ecuador can produce seven tons of proteins. Whereas soybeans produce only one ton of protein per hectare. “If we switch to Azolla, it could help in reducing deforestation in the Amazon. But taming Azolla and turning it into a crop is not easy,” he adds.
Henriette Schluepmann, a molecular plant biologist at Utrecht University in the Netherlands, believes that Azolla could replace soybeans and chemical fertilizers someday — only if researchers can achieve yield stability in controlled environments over long durations.
“In a country like the Netherlands that is surrounded by water with high levels of phosphates, it makes sense to grow Azolla as a substitute for soybeans,” says Schluepmann. “For that to happen, we need massive investments to understand these ferns’ reproductive system and how to replicate that within aquaculture systems on a large scale.”
Pollution control and carbon sequestration
Currently, Schluepmann and her team are growing Azolla in a plant nursery or closed system before transferring the ferns to flooded fields. So far, they have been able to continuously grow Azolla without any major setbacks for a total of 155 days. Taking care of these plants’ well-being is an uphill struggle.
Unlike most plants, Azolla does not grow from seeds because it contains female and male spores that tend to split instead of reproducing. To add to that, growing Azolla on a large scale in controlled environments makes the floating plants extremely vulnerable to insect infestations and fungi attacks.
“Even though it is easier to grow Azolla on a non-industrial scale, the long and tedious cultivation process is often in conflict with human rights,” she says. Farms in developing countries such as Indonesia sometimes use child labor for cultivating Azolla.”
History has taught us that the uncontrolled growth of Azolla plants deprives marine ecosystems of sunlight and chokes life underneath them. But researchers like Schluepmann and Bujak are optimistic that even on a much smaller scale, Azolla can put up a fight against human-driven climate change.
Schluepmann discovered an insecticide that can control Azolla blooms. But in the wild, this aquatic fern grows relentlessly in polluted rivers and lakes and has gained a notorious reputation as an invasive weed. Countries like Portugal and the UK banned Azolla after experiencing severe blooms in rivers that snuffed out local marine life.
“Azolla has been misunderstood as a nuisance. But in reality, it is highly beneficial for purifying water,” says Bujak. Through a process called phytoremediation, Azolla locks up pollutants like excess nitrogen and phosphorus and stops toxic algal blooms from occurring in rivers and lakes.
A 2018 study found that Azolla can decrease nitrogen and phosphorus levels in wastewater by 33 percent and 40.5 percent, respectively. While harmful algae like phytoplankton produce toxins and release noxious gases, Azolla automatically blocks any toxins that its cyanobacteria, Anabaena, might produce.
“In our labs, we observed that Azolla works effectively in treating wastewater,” explains Schluepmann. “Once we gain a better understanding of Azolla aquaculture, we can also use it for carbon capture and storage. But in Europe, we would have to use the entire Baltic Sea to make a difference.”
Planting massive amounts of these prehistoric ferns in any of the Northern great water bodies is out of the question. After all, history has taught us that the uncontrolled growth of Azolla plants deprives marine ecosystems of sunlight and chokes life underneath them. But researchers like Schluepmann and Bujak are optimistic that even on a much smaller scale, Azolla can put up a fight against human-driven climate change.
Traditional carbon capture and storage methods are not only expensive but also inefficient and could increase air pollution. According to Bujak’s estimates, Azolla can sequester 10 metric tonnes of carbon dioxide per hectare annually, which is 10 times the average capacity of grasslands.
“Anyone can set up their own DIY carbon capture and storage system by growing Azolla in shallow water. After harvesting and compressing the plants, carbon dioxide gets stored permanently,” says Bujak.
He envisions scaling up this process by setting up “Azolla hubs” in mega-cities where the plants are grown in shallow trays stacked on top of each other with vertical farming systems built within multi-story buildings. The compressed Azolla plants can then be converted into a biofuel, fertilizer, livestock feed, or biochar for sequestering carbon dioxide.
“Using Azolla to mitigate climate change might sound a bit too simple. But that is not the case,” Bujak adds. “At a microscopic level, extremely complicated biochemical reactions are constantly occurring inside the plant’s cells that machines or technology cannot replicate yet.”
Through Azolla, scientists hope to work with nature by tapping into four billion years of evolution.
A new virus has emerged and stoked fears of another pandemic: monkeypox. Since May 2022, it has been detected in 29 U.S. states, the District of Columbia, and Puerto Rico among international travelers and their close contacts. On a worldwide scale, as of June 30, there have been 5,323 cases in 52 countries.
The good news: An existing vaccine can go a long way toward preventing a catastrophic outbreak. Because monkeypox is a close relative of smallpox, the same vaccine can be used—and it is about 85 percent effective against the virus, according to the World Health Organization (WHO).
Also on the plus side, monkeypox is less contagious with milder illness than smallpox and, compared to COVID-19, produces more telltale signs. Scientists think that a “ring” vaccination strategy can be used when these signs appear to help with squelching this alarming outbreak.
How it’s transmitted
Monkeypox spreads between people primarily through direct contact with infectious sores, scabs, or bodily fluids. People also can catch it through respiratory secretions during prolonged, face-to-face contact, according to the Centers for Disease Control and Prevention (CDC).
As of June 30, there have been 396 documented monkeypox cases in the U.S., and the CDC has activated its Emergency Operations Center to mobilize additional personnel and resources. The U.S. Department of Health and Human Services is aiming to boost testing capacity and accessibility. No Americans have died from monkeypox during this outbreak but, during the COVID-19 pandemic (February 2020 to date), Africa has documented 12,141 cases and 363 deaths from monkeypox.
Ring vaccination proved effective in curbing the smallpox and Ebola outbreaks. As the monkeypox threat continues to loom, scientists view this as the best vaccine approach.
A person infected with monkeypox typically has symptoms—for instance, fever and chills—in a contagious state, so knowing when to avoid close contact with others makes it easier to curtail than COVID-19.
Advantages of ring vaccination
For this reason, it’s feasible to vaccinate a “ring” of people around the infected individual rather than inoculating large swaths of the population. Ring vaccination proved effective in curbing the smallpox and Ebola outbreaks. As the monkeypox threat continues to loom, scientists view this as the best vaccine approach.
With many infections, “it normally would make sense to everyone to vaccinate more widely,” says Wesley C. Van Voorhis, a professor and director of the Center for Emerging and Re-emerging Infectious Diseases at the University of Washington School of Medicine in Seattle. However, “in this case, ring vaccination may be sufficient to contain the outbreak and also minimize the rare, but potentially serious side effects of the smallpox/monkeypox vaccine.”
There are two licensed smallpox vaccines in the United States: ACAM2000 (live Vaccina virus) and JYNNEOS (live virus non-replicating). The ACAM 2000, Van Voorhis says, is the old smallpox vaccine that, in rare instances, could spread diffusely within the body and cause heart problems, as well as severe rash in people with eczema or serious infection in immunocompromised patients.
To prevent organ damage, the current recommendation would be to use the JYNNEOS vaccine, says Phyllis Kanki, a professor of health sciences in the division of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health. However, according to a report on the CDC’s website, people with immunocompromising conditions could have a higher risk of getting a severe case of monkeypox, despite being vaccinated, and “might be less likely to mount an effective response after any vaccination, including after JYNNEOS.”
In the late 1960s, the ring vaccination strategy became part of the WHO’s mission to globally eradicate smallpox, with the last known natural case described in Somalia in 1977. Ring vaccination can also refer to how a clinical trial is designed, as was the case in 2015, when this approach was used for researching the benefits of an investigational Ebola vaccine in Guinea, Kanki says.
“Since Monkeypox spreads by close contact and we have an effective vaccine, vaccinating high-risk individuals and their contacts may be a good strategy to limit transmission,” she says, adding that privacy is an important ethical principle that comes into play, as people with monkeypox would need to disclose their close contacts so that they could benefit from ring vaccination.
Rapid identification of cases and contacts—along with their cooperation—is essential for ring vaccination to be effective. Although mass vaccination also may work, the risk of infection to most of the population remains low while supply of the JYNNEOS vaccine is limited, says Stanley Deresinski, a clinical professor of medicine in the Infectious Disease Clinic at Stanford University School of Medicine.
Other strategies for preventing transmission
Ideally, the vaccine should be administered within four days of an exposure, but it’s recommended for up to 14 days. The WHO also advocates more widespread vaccination campaigns in the population segment with the most cases so far: men who engage in sex with other men.
The virus appears to be spreading in sexual networks, which differs from what was seen in previously reported outbreaks of monkeypox (outside of Africa), where risk was associated with travel to central or west Africa or various types of contact with individuals or animals from those locales. There is no evidence of transmission by food, but contaminated articles in the environment such as bedding are potential sources of the virus, Deresinski says.
Severe cases of monkeypox can occur, but “transmission of the virus requires close contact,” he says. “There is no evidence of aerosol transmission, as occurs with SARS-CoV-2, although it must be remembered that the smallpox virus, a close relative of monkeypox, was transmitted by aerosol.”
Deresinski points to the fact that in 2003, monkeypox was introduced into the U.S. through imports from Ghana of infected small mammals, such as Gambian giant rats, as pets. They infected prairie dogs, which also were sold as pets and, ultimately, this resulted in 37 confirmed transmissions to humans and 10 probable cases. A CDC investigation identified no cases of human-to-human transmission. Then, in 2021, a traveler flew from Nigeria to Dallas through Atlanta, developing skin lesions several days after arrival. Another CDC investigation yielded 223 contacts, although 85 percent were deemed to be at only minimal risk and the remainder at intermediate risk. No new cases were identified.
How much should we be worried
But how serious of a threat is monkeypox this time around? “Right now, the risk to the general public is very low,” says Scott Roberts, an assistant professor and associate medical director of infection prevention at Yale School of Medicine. “Monkeypox is spread through direct contact with infected skin lesions or through close contact for a prolonged period of time with an infected person. It is much less transmissible than COVID-19.”
The monkeypox incubation period—the time from infection until the onset of symptoms—is typically seven to 14 days but can range from five to 21 days, compared with only three days for the Omicron variant of COVID-19. With such a long incubation, there is a larger window to conduct contact tracing and vaccinate people before symptoms appear, which can prevent infection or lessen the severity.
But symptoms may present atypically or recognition may be delayed. “Ring vaccination works best with 100 percent adherence, and in the absence of a mandate, this is not achievable,” Roberts says.
At the outset of infection, symptoms include fever, chills, and fatigue. Several days later, a rash becomes noticeable, usually beginning on the face and spreading to other parts of the body, he says. The rash starts as flat lesions that raise and develop fluid, similar to manifestations of chickenpox. Once the rash scabs and falls off, a person is no longer contagious.
“It's an uncomfortable infection,” says Van Voorhis, the University of Washington School of Medicine professor. There may be swollen lymph nodes. Sores and rash are often limited to the genitals and areas around the mouth or rectum, suggesting intimate contact as the source of spread.
Symptoms of monkeypox usually last from two to four weeks. The WHO estimated that fatalities range from 3 to 6 percent. Although it’s believed to infect various animal species, including rodents and monkeys in west and central Africa, “the animal reservoir for the virus is unknown,” says Kanki, the Harvard T.H. Chan School of Public Health professor.
Too often, viruses originate in parts of the world that are too poor to grapple with them and may lack the resources to invest in vaccines and treatments. “This disease is endemic in central and west Africa, and it has basically been ignored until it jumped to the north and infected Europeans, Americans, and Canadians,” Van Voorhis says. “We have to do a better job in health care and prevention all over the world. This is the kind of thing that comes back to bite us.”