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Juan Lama
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Early in 2017, a team of medical personnel, including doctors, nurses and volunteers, returned home to Florida after volunteering at a clinic in Haiti. Soon after their return, 20 members of the team began to feel a bit under the weather. "They had a slight fever and didn't feel 100% right," says virologist John Lednicky at the University of Florida. "But they weren't very sick." At the time, Zika virus was circulating in Haiti, and health officials were worried the travelers might have been infected, potentially importing the mosquito-borne illness to Florida. So officials took urine samples from each traveler and asked Lednicky to test for Zika. Lednicky ran the standard PCR tests for the virus, and they all came back negative. But he wasn't satisfied. He had a hunch that the urine samples did contain a virus — not Zika but something else. So he took a little bit of the urine from six of the travelers and added it to a special solution of monkey cells. The goal was deceptively simple: to see if any viruses in the urine would infect the monkey cells, start replicating and grow to detectable levels. Then Lednicky could collect the virus's genes and identify it. "This is what we do in our lab," Lednicky says. "We cast a wide net. We try to isolate viruses. And oftentimes, when we do that, the unexpected happens." Indeed, the unexpected occurred. "We found a coronavirus," he says. And not just any coronavirus, but one that many scientists believe may be a new human pathogen — likely the 8th coronavirus known to cause disease in people. Turns out, this coronavirus in the Haiti travelers has cropped up previously, on the other side of the globe. Coronavirus From Dogs Likely Causes Pneumonia In Kids Back in May, scientists at Duke University, reported they had detected a nearly identical virus coronavirus in children at a Malaysian hospital. The researchers found the virus in the upper respiratory tract of 3% of the 301 patients they tested in 2017 and 2018. The genetic sequence of the Malaysian virus suggested it likely originated in dogs and then jumped into people. "The majority of the genome was canine coronavirus," virologist Anastasia Vlasova told NPR in May. Although the findings sounded alarming, the researchers had no evidence that the virus could spread between people or that it was widespread around the world. "These human infections with ... canine coronaviruses appear to be isolated incidents which did not lead to extensive human transmission," virologist Vincent Racaniello wrote on the Virology Blog. Now Lednicky and his colleagues have found an almost identical virus infecting people 11,000 miles away-- at the same time. The genetic sequence of the virus in Haiti is 99.4% identical to the one in Malaysia. Lednicky and his colleagues reported this past Sunday in the journal Clinical Infectious Diseases. And the big question is: How does a dog virus in Malaysia wind up in doctors and nurses in Haiti? A Widespread Virus, But How It Spreads Is A Mystery "The virus probably circulates widely, but no one has paid attention to it," Lednicky says. He suspects it's all over the world. And if you've been around dogs frequently you might have been infected with this virus — or developed an immunity to it by exposure to similar virus. "We'll know when scientists start looking for antibodies inside older blood samples taken from patients with respiratory disease. How many of them were misdiagnosed all along?" Some scientists also think doctors and researchers should start actively looking for this virus in patients. "I think that's important for several reasons," says virologist Linda Saif at Ohio State University, who has studied coronaviruses for about 40 years. "No. 1, this virus has been associated with a number of pneumonia cases in children, and no. 2, we really don't know if it can transmit from human to human," she adds. The fact that scientists detected the almost-identical viruses in both Haiti and Malaysia, at the same time, suggests the virus does spread between people, Saif says. "There's a temporal sequence here. These two viruses — which are very, very similar — have been detected in a similar time frame but in widely separated regions of the world," she explains. That could happen if a nearly-identical virus was circulating in dogs in both Haiti and Malaysia and then jumped over to people in both countries during the same year. "I would be very surprised if that happened," Saif says. The second hypothesis is that the virus is circulating in people, at low levels, in many parts of the world, under the radar. "That hypothesis is more likely," Saif says. If that hypothesis turns out to be true, this canine coronavirus will be the eighth coronavirus known to spread among humans. Why This Finding Is Good News On the surface, these new findings sound like horrible news. The last thing the world needs right now is another coronavirus that may trigger pneumonia in children. But Jonna Mazet says it's actually good news because it means scientists have caught this virus before it has caused a big problem. "The very exciting part is that people are starting to do virus discovery and characterization, even when large groups of people aren't dying and or getting severely ill, which is how most virus discovery has happened in the past," says Mazet, who's an epidemiologist at the University of California, Davis and the founding executive director of the One Health Institute there. By finding this virus early, scientists now have time to study it, create tools to diagnose it and understand what it might take to stop it. Although it's not a cause for deep concern at this time, there's always the risk the virus could evolve over time and become a bigger problem, Mazet says, as was likely the case with SARS-CoV-2. "Almost certainly, SARS-CoV-2 was circulating for quite some time and making people either a tiny bit sick or not sick enough to be noticed," she says. If scientists had detected it at this stage, perhaps the world would have had time to develop a test for it, some promising treatments and even a preliminary vaccine. Perhaps the pandemic would have taken a much different — perhaps less deadly course. "We need to find these novel viruses well before they fully adapt to humans and become a pandemic problem," writes epidemiologist Gregory Gray, from the University of Texas Medical Branch, in an email to NPR. "Fortunately, today we have the tools to both detect and evaluate the risk of such novel viruses. We just need the political will and financial support to do so."
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Juan Lama
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Starting Wednesday, Finland launches a coronavirus-sniffing-dog pilot program at Helsinki Airport. The voluntary tests will reportedly deliver results in seconds, will require no contact with the dogs and take less than a minute of travelers' time. The voluntary canine tests will deliver results within 10 seconds, and require less than a minute of travelers’ time, said Anna Hielm-Björkman, a researcher at the University of Helsinki who is using the trial to gather data. Researchers in other countries, including the United States and the United Arab Emirates, are studying canine coronavirus tests. But the Finnish trial is among the largest in scale and furthest along. In Dubai, health officials this summer began using dogs to analyze sweat samples from randomly selected air travelers, with more than 90% accuracy, according to initial results. Changes in health can affect the way people smell, researchers say. Dogs long have been valued for their ability to sniff for drugs and bombs, and have proved able to detect cancers, infections and other health problems. Researchers at the University of Helsinki this year found indications that dogs can detect the virus. Scientists say only large-scale trials, such as the one to begin Wednesday, can demonstrate how effective the method will be in practice. As in Dubai, the dogs to be deployed in Helsinki will sniff sweat samples and will not come into contact with travelers. People who agree to the test will swab their necks to produce a sample, to submit through an opening in a wall, said Hielm-Björkman. Regardless of whether they test positive, they will be urged to take a standard polymerase chain reaction (PCR) COVID-19 test so researchers can monitor the dogs’ accuracy. All tests are free for travelers arriving at the airport. Hielm-Björkman said the dogs, according to preliminary research, may be better at detecting coronavirus infections, which can cause the illness COVID-19, than PCR and antibody tests. They “can also find [people] that are not yet PCR positive, but will become PCR positive within a week,” she said. Virpi Perälä, a representative for Evidensia Elainlaakaripalvelut, a network of veterinary clinics that funded the first stage of the trial, during which the initial cohort of dogs were trained, said more funding would be needed to grow the project, depending on initial results. Out of the 16 dogs trained, four are ready to work. Six others are still in training, with another six found to be unsuitable for a noisy airport environment. Experts have warned that canine tests, however effective, can be difficult to scale. Training is time-consuming and expensive. Even so, researchers are optimistic that it will come to play a roll, even if it cannot alleviate the demands on the world’s strained testing systems. One of the aims of the upcoming trial, said Hielm-Björkman, is to gather observations on how long the dogs can work in shifts. “You see very easily on a dog when it starts to get tired,” she said.
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Juan Lama
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In a Finnish study, dogs learned to recognize the distinctive odor of a coronavirus infection. In the future, dogs might be able to detect infected people in nursing homes or at airports. In a pilot study at the University of Helsinki, dogs trained as medical diagnostic assistants were taught to recognize the previously unknown odor signature of the COVID-19 disease caused by the novel coronavirus. And they learned with astonishing success: After only a few weeks, the first dogs were able to accurately distinguish urine samples from COVID-19 patients from urine samples of healthy individuals. "We have solid experience in training disease-related scent detection dogs. It was fantastic to see how fast the dogs took to the new smell," says DogRisk group leader Anna Hielm-Björkman. After only a short time, the animals identified the urine of people infected by the novel coronavirus, known as SARS-CoV-2, almost as reliably as a standard PCR test. The Finnish scientists are now preparing a randomized, double-blind study in which the dogs will sniff a larger number of patient samples. Only then will the scent tests be used in clinical practice. The very rapid and promising findings from Finland are also important for other research teams, such as those in Great Britain and France, who are training sniffer dogs to detect COVID-19. Fellow researchers from the German Assistance Dog Center (TARSQ) have also benefited from the Finnish results. "No one could tell us with certainty whether training with the aggressive virus is dangerous or not for humans and dogs. We wanted to gather more information first before we started training because the German virologists advised us against it — after all, so little is known about the virus so far," explains Luca Barrett from TARSQ. It is still unclear which substances in urine produce the apparently characteristic COVID-19 odor. Since SARS-CoV-2 not only attacks the lungs, but also causes damage to blood vessels, kidneys and other organs, it is assumed that the patients' urine odor also changes. This is something which the dogs, with their highly sensitive olfactory organs, notice immediately. Certain diseases appear to have a specific olfactory signature that trained dogs can sniff out with amazing accuracy, Barrett says. "According to one study, dogs can detect breast cancer with a 93% probability, for example. And lung cancer with a 97% probability," she says. See also study in BMC Inf. Dis. (July 23, 2020): https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-020-05281-3
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The dogs are already trained to detect odours of cancers, malaria and Parkinson's disease. The first phase of the trial will be led by the London School of Hygiene & Tropical Medicine, along with the charity and Durham University. It has been backed with £500,000 of government funding. Innovation minister Lord Bethell said he hoped the dogs could provide "speedy results" as part of the government's wider testing strategy. The trial will explore whether the "Covid dogs" - made up of Labradors and cocker spaniels - can spot the virus in humans from odour samples before symptoms appear. It will establish whether so-called bio-detection dogs, which could each screen up to 250 people per hour, could be used as a new early warning measure to detect Covid-19 in the future. The first phase will involve NHS staff in London hospitals collecting odour samples from those infected with coronavirus and those who are uninfected. Samples of breath and body odour could come from a number of sources, including used face masks....
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Juan Lama
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Just as gene therapy finally seems to be living up to its promise, a study has revived a lingering worry about the viral vessel that many efforts rely on to ferry therapeutic genes into patients. This “vector,” a stripped-down version of adeno-associated virus (AAV), was thought to be safe because it rarely knits the human DNA it carries into a cell’s chromosomes, where it might activate cancer-causing genes. But a study of dogs with hemophilia, treated with AAV up to 10 years earlier, has shown that the vector can readily insert its payload into the host’s DNA near genes that control cell growth. The new data, described in a conference talk last month by a Philadelphia-based research team, are “good news and bad news,” says gene therapy researcher Charles Venditti of the National Human Genome Research Institute. By slipping into the chromosomes rather than floating free, the therapeutic DNA might have longer lasting benefits. Integration “happens and it may actually be essential for long-term expression” of a needed protein, says physician-scientist David Lillicrap of Queen’s University, who attended the 9 December 2019 talk at the annual meeting of the American Society of Hematology (ASH) in Orlando, Florida. But the findings also fuel a debate about whether AAV vectors could pose an unacceptable cancer risk. “We don’t know enough yet” to say, according to Lillicrap. Another viral vector, used in some early gene therapy trials, caused cancer in a few children after it integrated its cargo into the chromosomes. AAV seemed to be a safer alternative because genes introduced by the modified virus generally become a free-floating loop, known as an episome, in the cell’s nucleus. AAV vectors have helped drive the recent surge of successful gene therapies. These include one approved by the U.S. Food and Drug Administration last year for spinal muscular atrophy, a fatal childhood neurological disease, and a treatment for the blood-clotting disorder hemophilia B that’s expected to receive FDA approval this year. In the hemophilia treatment, AAV infects liver cells and turns the organ into a factory for making the clotting protein that patients depend on. Yet doubts about AAV’s safety have simmered for nearly 20 years, since a study found that in newborn mice given high doses of the virus, it could integrate its genetic cargo into the animals’ DNA and cause liver cancer. Many gene therapists argued that findings in newborn mice are not relevant to human adults. But the new warning comes from larger, older animals: adult dogs with hemophilia A, in which a clotting protein called factor VIII is missing. In seven of nine such dogs, AAV vectors successfully supplied a replacement copy of the gene for factor VIII and restored stable production of the molecule. In two of those dogs, however, blood levels rose further after about 3 years, reaching about four times the original level by 7 to 8 years, gene therapy researcher Denise Sabatino of the Children’s Hospital of Philadelphia reported at the ASH meeting. After ending the experiment and studying the livers of six dogs, her team found that in every one of them, AAV-ferried DNA—the factor VIII gene or, more often, fragments of regulatory sequences—had integrated in many spots across the genome in the dogs’ liver cells, sometimes near genes affecting cell growth. Some of those cells had divided more than other cells, forming pockets of multiple cells or “clones” in some animals. Sabatino’s team suspects—although it can’t prove—that the insertions activated growth genes, explaining both the clones and the rise in blood levels of factor VIII in the two dogs...... Published in Science (Jan 6, 2019): https://doi.org/10.1126/science.aba7696
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Juan Lama
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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
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Cats and dogs are just as likely to be infected with SARS-CoV-2 as people are, according to a survey in northern Italy that is the largest study of pets so far. Nicola Decaro at the University of Bari and his colleagues took nose, throat or rectal swabs of 540 dogs and 277 cats in northern Italy between March and May (E. I. Patterson et al. Preprint at bioRxiv http://doi.org/d4r7; 2020). The animals lived in homes with infected people, or in regions severely affected by COVID-19. Nicola Decaro at the University of Bari and his colleagues took nose, throat or rectal swabs of 540 dogs and 277 cats in northern Italy between March and May (E. I. Patterson et al. Preprint at bioRxiv http://doi.org/d4r7; 2020). The animals lived in homes with infected people, or in regions severely affected by COVID-19. Infection rates among cats and dogs were comparable with those among people in Europe at the time of testing, suggesting that it is not unusual for pets to be infected. The findings have not yet been peer reviewed. Preprint available at bioRxiv (July 23, 2020): https://doi.org/10.1101/2020.07.21.214346
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Juan Lama
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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
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SARS-CoV-2 emerged in Wuhan in December 2019 and caused the pandemic respiratory disease, COVID-191,2. In 2003, the closely related SARS-CoV had been detected in domestic cats and a dog3. However, little is known about the susceptibility of domestic pet mammals to SARS-CoV-2. Two out of fifteen dogs from households with confirmed human cases of COVID-19 in Hong Kong SAR were found to be infected using quantitative RT–PCR, serology, sequencing the viral genome, and in one dog, virus isolation. SARS-CoV-2 RNA was detected in a 17-year-old neutered male Pomeranian from five nasal swabs collected over a 13-day period. A 2.5-year-old male German Shepherd dog had SARS CoV-2 RNA on two occasions and virus was isolated from nasal and oral swabs. Both dogs had antibody responses detected using plaque reduction neutralization assays. Viral genetic sequences of viruses from the two dogs were identical to the virus detected in the respective human cases. The animals remained asymptomatic during quarantine. The evidence suggests that these are instances of human-to-animal transmission of SARS-CoV-2. It is unclear whether infected dogs can transmit the virus to other animals or back to humans. Published in Nature (May 14, 2020): https://doi.org/10.1038/s41586-020-2334-5
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A gene therapy being developed at Penn Medicine to treat Duchenne muscular dystrophy (DMD) successfully and safely stopped the severe muscle deterioration associated with the rare, genetic disease in both small and large animal models, according to a first-of-its-kind study from Penn Medicine researchers. The findings, published online today in Nature Medicine, puts the field within closer reach of a safe and effective gene therapy that uses a "substitute" protein without triggering immune responses known to hinder other therapeutic approaches. Found mostly in boys, DMD is caused by mutations in a sex-linked gene that stop production of a muscle-building protein known as dystrophin. Without it, muscles progressively deteriorate and weaken starting at a very young age and only worsen from there. Most patients aren't able to walk by age 12 and die of heart or respiratory failure by the time they reach their 30s, though respirators have helped some live longer. With their modified gene therapy approach, a multidisciplinary team from the Perelman School of Medicine at the University of Pennsylvania engineered adeno-associated virus (AAV) vectors to deliver a "substitute" protein for dystrophin in small and large animal DMD models to keep the muscles intact. The synthetic substitute, based on a naturally occurring protein called utrophin, proved to be an effective and safe alternative, as it protected muscle in mice and dogs with naturally occurring DMD-like mutations, including a large deletion that closely mirrors the large dystrophin deletions found in humans. "For the first time, we've shown how a carefully constructed version of a dystrophin-related protein can safely prevent the breakdown of muscle and maintain its function over time in the most informative animal models. This discovery has important implications for gene therapy and how we work toward safe and effective treatments for muscular dystrophy," said senior author Hansell H. Stedman, MD, an associate professor of Surgery. "With these results, we have a strong rationale to move this forward into human clinical trials." Restoring levels of dystrophin with gene therapy and other techniques have been under scrutiny due to the immune system's adverse reaction to additions it deems foreign. DMD patients have little to none of this protein, so their bodies can attack well-intentioned direct replacement proteins because they are seen as foreign. However, because dystrophin's distant cousin utrophin is expressed in other places in the body, it was thought that the immune system wouldn't view it as a threat. The Penn team showed this to be true in rigorous, randomized mouse and dog studies. Delivering a single-dose treatment of synthetic utrophin with the AAV vector to newborn mice showed distribution of the protein throughout the body, no signs of toxicity, and complete suppression of all signs of DMD, compared to untreated mice. The mice also sustained expression of utrophin in skeletal and cardiac muscles throughout that time, and physical tests in the mice supported the sustained muscle function..... Published in Nature Medicine on October 7, 2019: https://doi.org/10.1038/s41591-019-0594-0
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