Taxi drivers and health workers are among 

the most exposed to the coronavirus

Bartenders, waiters, drivers, nurses and dentists.

 People with occupations that require contact with customers and patients are more exposed to the coronavirus.

Healthcare personnel are among the employees with higher infection rates for COVID-19 compared to the general population of working age. 

(Photo: Gorm Kallestad/NTB)

Ida Irene Bergstrøm

JOURNALIST
NTB NORWEGIAN NEWS AGENCY
Saturday 14. november 2020 - 

Those who work in the healthcare services, in bars and restaurants, and in public transport are among the workers who have been the most exposed to the coronavirus, according to a new study by the Norwegian Institute of Public Health, NIPH.

Healthcare personnel had the most confirmed cases per 1000 employees before this summer, while workers in bars and restaurants have had the most confirmed cases per 1000 employees after the summer.

Taxi drivers, bus drivers and tram drivers have also been more infected than in the rest of the population of working age.
1,5-three times more infections

Between February and July, there were 2,3 registered cases of COVID-19 per 1000 people aged between 20-70 in Norway.

For healthcare personnel the corresponding number was 3,5-6,5 cases per 1000, and for taxi drivers it was 3,4-5,5 cases.

This equals 1,5 to three times more infections than the general population.

Between July and November, the spread of the virus increased somewhat in Norway, to 2,6 cases per 1000 people aged between 20-70 years.

In this period, workers in bars and restaurants, as well as flight and boat attendants, were the most exposed to COVID-19. In these groups, registered cases were between 6,2-8,9 per 1000 employees.

During this period the rates of infection among health workers were the same as for the general population.

Teachers had the same level of infection as the general population both before and after the summer.

Schools were closed in Norway during the lockdown that started on March 12th, and only opened up just before summer holidays started. Schools have been open during the fall and are still open, despite the stricter measures that have been implemented in Norway during recent weeks.
Testing criteria and better protection

"The difference between the first and second wave may be due to changes in the test criteria," says Karin Magnusson in a press release from NIPH. She is a researcher at the NIPH and the first author of the study.

During the first period of the pandemic in Norway and elsewhere in the world, there was a shortage of test equipment, and patients, risk groups and healthcare personnel were prioritized for testing. But this fall there has been no lack of testing equipment or facilities in Norway, and close contacts and people with mild symptoms can get tested.

Another explanation, according to Magnusson, could be that fewer people have travelled abroad.

“The high proportion of doctors who were infected in the first period may, for example, have been infected on holiday in Italy, and not in Norway at the doctor's office”, Magnusson says in the press release.

“One explanation could also be better protection of healthcare personnel”, she says.

More hospitalisations among dentists


There were no differences between occupational groups for severe COVID-19 disease and admissions to hospital. One exception was dentists who had more hospital admissions than other occupational groups.

“This raises the question of whether being infected with a large dose of virus from an individual increases the risk of developing a more serious disease”, Magnusson says in the press release, adding that “but the numbers are low and therefore uncertain”.

Infections on the rise

Norway has experienced a severe increase in infections, as the rest of Europe, during the past few weeks. Strict measures are in place, both nationally and locally, for instance in the largest cities Oslo and Bergen.

Border controls have become stricter, with demands of ten days at a quarantine hotel as well as testing. Home office when possible is mandatory, and there are limits as to how many people are allowed to meet in private homes - five in Bergen, and ten in Oslo. Authorities have also warned that people will be fined if they violate the rules.

At home and at the office

Norwegians are now most often infected in private homes – this represents 41 per cent of cases. Then comes work and universities, with 17 per cent of the cases, followed by private events with 10 per cent of cases.

4 per cent of the cases have been traced to bars and restaurants and 3 per cent to kindergartens and schools.

The source of infection is unknown in 15 per cent of the cases.

SARS-CoV-2 transmission model offers decision-making pathways for safe school opening

Shanghai-based mathematical model predicts when schools can be open/reopen

LARNER COLLEGE OF MEDICINE AT THE UNIVERSITY OF VERMONT

Research News

 

Can schools safely remain open or reopen during periods of significant community spread of COVID-19? According to predictions from a model of SARS-CoV-2 transmission in the school setting, yes - if appropriate precautions are followed both in school and in the community.

The study results are published in BMC Public Health.

School closures during the COVID-19 pandemic have been based predominantly on models of pandemic influenza transmission. However, say the study's authors, recent evidence suggests that "children under the age of 10, are less susceptible to SARS-CoV-2 infection and rarely transmit the infection to adults or schoolmates."

For their study, University of Vermont researchers adapted a previously-published model using contact data from Shanghai, China to investigate the impact of open schools on community spread of SARS-CoV-2 infection.

A critical feature of the model is the measurement of contact structure across all age groups, with a focus on the rate of daily contacts in the community and social contacts in school - and how a reduction in contact frequency affects transmission risk.

The team combined contact patterns observed between different age groups during pre- and post-pandemic "lockdown" periods to simulate various levels of school reopening and also tested these effects across a range of estimates of lower susceptibility rates to infection in younger children.

According to first author Benjamin Lee, M.D., associate professor of pediatrics and a pediatric infectious diseases specialist, the model helped identify conditions that would support keeping schools open. Ideally, he said, the average number of daily social contacts in the community needs to be reduced to about 40 percent of pre-pandemic baseline, and total contacts for children aged 10 to 19 needs to be reduced to 33 percent of pre-pandemic baseline. If this can be achieved, having open schools would be feasible even starting from a point of significant community transmission.

"In other words, necessary restrictions in the community with careful mitigation for older kids is the trade-off that will enable schools to remain open," said Lee. "Schools should be the last to close and first to re-open."

The study demonstrates how considering a combination of different measures is beneficial in creating a path to having schools be open to the extent possible, within a broader set of restrictions.

"It's not just about the scale of restrictions, but also about how targeted these restrictions are, because the structure of contacts matters," said senior author Laurent Hébert-Dufresne, Ph.D., assistant professor of computer science.

"This study provides a basic proof-of-principle that we believe can be applicable to many settings that have similar contact structures," said Lee.

###

SFU researchers examine which approaches are most effective at reducing COVID-19 spread

Social bubbles and masks more situation-dependent in terms of effectiveness

SIMON FRASER UNIVERSITY

Research News

 

Simon Fraser University professors Paul Tupper and Caroline Colijn have found that physical distancing is universally effective at reducing the spread of COVID-19, while social bubbles and masks are more situation-dependent.

The researchers developed a model to test the effectiveness of measures such as physical distancing, masks or social bubbles when used in various settings.

Their paper was published Nov. 19 in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

They introduce the concept of "event R," which is the expected number of people who become infected with COVID-19 from one individual at an event.

Tupper and Colijn look at factors such as transmission intensity, duration of exposure, the proximity of individuals and degree of mixing - then examine what methods are most effective at preventing transmission in each circumstance.

The researchers incorporated data from reports of outbreaks at a range of events, such as parties, meals, nightclubs, public transit and restaurants. The researchers say that an individual's chances of becoming infected with COVID-19 depend heavily on the transmission rate and the duration - the amount of time spent in a particular setting.

Events were categorized as saturating (high transmission probability) or linear (low transmission probability). Examples of high transmission settings include bars, nightclubs and overcrowded workplaces while low transmission settings include public transit with masks, distancing in restaurants and outdoor activities.

The model suggests that physical distancing was effective at reducing COVID-19 transmission in all settings but the effectiveness of social bubbles depends on whether chances of transmission are high or low.

In settings where there is mixing and the probability of transmission is high, such as crowded indoor workplaces, bars and nightclubs and high schools, having strict social bubbles can help reduce the spread of COVID-19.

The researchers found that social bubbles are less effective in low transmission settings or activities where there is mixing, such as engaging in outdoor activities, working in spaced offices or travelling on public transportation wearing masks.

They note that masks and other physical barriers may be less effective in saturating, high transmission settings (parties, choirs, restaurant kitchens, crowded offices, nightclubs and bars) because even if masks halve the transmission rates that may not have much impact on the transmission probability (and so on the number of infections).

The novel coronavirus is relatively new but the science continues to evolve and increase our knowledge of how to effectively treat and prevent this highly contagious virus. There is still much that we do not know and many areas requiring further study.

"It would be great to start collecting information from exposures and outbreaks: the number of attendees, the amount of mixing, the levels of crowding, the noise level and the duration of the event," says Colijn, who holds a Canada Research Chair in Mathematics for Evolution, Infection and Public Health.

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Frequent, rapid testing could cripple COVID within weeks, study shows

Research shows test turnaround-time, frequency far more important than sensitivity in curbing spread

UNIVERSITY OF COLORADO AT BOULDER

Research News

 

Testing half the population weekly with inexpensive, rapid-turnaround COVID-19 tests would drive the virus toward elimination within weeks-- even if those tests are significantly less sensitive than gold-standard clinical tests, according to a new study published today by University of Colorado Boulder and Harvard University researchers.

Such a strategy could lead to "personalized stay-at-home orders" without shutting down restaurants, bars, retail stores and schools, the authors said.

"Our big picture finding is that, when it comes to public health, it's better to have a less sensitive test with results today than a more sensitive one with results tomorrow," said lead author Daniel Larremore, an assistant professor of computer science at CU Boulder. "Rather than telling everyone to stay home so you can be sure that one person who is sick doesn't spread it, we could give only the contagious people stay-at-home orders so everyone else can go about their lives."

For the study, published in the journal Science Advances, Larremore teamed up with collaborators at CU's BioFrontiers Institute and the Harvard T.H. Chan School of Public Health to explore whether test sensitivity, frequency, or turnaround time is most important to curb the spread of COVID-19.

The researchers scoured available literature on how viral load climbs and falls inside the body during infection, when people tend to experience symptoms, and when they become contagious.

They then used mathematical modeling to forecast the impact of screening with different kinds of tests on three hypothetical scenarios: in 10,000 individuals; in a university-type setting of 20,000 people; and in a city of 8.4 million.

When it came to curbing spread, they found that frequency and turnaround time are much more important than test sensitivity.

For instance, in one scenario in a large city, widespread twice-weekly testing with a rapid but less sensitive test reduced the degree of infectiousness, or R0 ("R naught"), of the virus by 80%. But twice-weekly testing with a more sensitive PCR (polymerase chain reaction) test, which takes up to 48 hours to return results, reduced infectiousness by only 58%. When the amount of testing was the same, the rapid test always reduced infectiousness better than the slower, more sensitive PCR test.

That's because about two-thirds of infected people have no symptoms and as they await their results, they continue to spread the virus.

"This paper is one of the first to show we should worry less about test sensitivity and, when it comes to public health, prioritize frequency and turnaround," said senior co-author Roy Parker, director of the BioFrontiers Institute and a Howard Hughes Medical Institute investigator.

The study also demonstrates the power of frequent testing in shortening the pandemic and saving lives.

In one scenario, in which 4% of individuals in a city were already infected, rapid testing three out of four people every three days reduced the number ultimately infected by 88% and was "sufficient to drive the epidemic toward extinction within six weeks."

The study comes as companies and academic research centers are developing low-cost, rapid turnaround tests that could be deployed in large public settings or commercialized for do-it-yourself use.

Sensitivity levels vary widely. Antigen tests require a relatively high viral load - about 1,000 times as much virus compared to the PCR test -- to detect an infection. Another test, known as RT-lamp (reverse transcription loop-mediated isothermal amplification), can detect the virus at around 100 times as much virus compared to the PCR. The benchmark PCR test requires as little as 5,000 to 10,000 viral RNA copies per milliliter of sample, meaning it can catch the virus very early or very late.

In the past, federal regulators and the public have been reluctant to embrace rapid tests out of concern that they may miss cases early in infection. But, in reality, an infected person can go from 5,000 particles to 1 million viral RNA copies in 18 to 24 hours, said Parker.

"There is a very short window, early in infection, in which the PCR will detect the virus but something like an antigen or LAMP test won't," Parker said.

And during that time, the person often isn't contagious, he said.

"These rapid tests are contagiousness tests," said senior co-author Dr. Michael Mina, an assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health. "They are extremely effective in detecting COVID-19 when people are contagious."

They are also affordable, he added. The rapid tests can cost as little as $1 each and return results in 15 minutes. Some PCR tests can take several days.

Mina envisions a day when the government sends simple, cheap DIY tests to every home. Even if half of Americans tested themselves weekly and self-isolated if positive, the result would be profound, he said.

"Within a few weeks we could see this outbreak going from huge numbers of cases to very manageable levels," Mina said.

Rapid testing could also be the key to breathing life back into former super spreader threats like football stadiums, concert venues and airports, with patrons testing themselves on the way in and still wearing masks as a precautionary measure, Larremore said.

"Less than .1% of the current cost of this virus would enable frequent testing for the whole of the U.S. population for a year," said Mina, referencing a recent Harvard economic analysis.

The authors say they are heartened to see that several countries have already begun testing all of their citizens, and hopeful that the new U.S. administration has named rapid testing as a priority.

"It's time to shift the mentality around testing from thinking of a COVID test as something you get when you think you are sick to thinking of it as a vital tool to break transmission chains and keep the economy open," Larremore said.

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For COVID-19 surveillance, test frequency and turnaround time are paramount, modeling suggests

Test sensitivity is secondary to frequency and turnaround time for COVID-19 screening

AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE

Research News

 

For COVID-19 Surveillance, Test Frequency and Turnaround Time Are Paramount, Modeling Suggests Speed of test results and frequency of testing are paramount for effective COVID-19 surveillance, suggests a new study that modeled trade-offs in test sensitivity, test frequency, and sample-to-answer reporting time, in select scenarios. Test sensitivity is secondary to these factors in the scenarios studied, the authors say. "If the availability of point-of-care or self-administered screening tests leads to faster turnaround time or more frequent testing, our results suggest that they would have high epidemiological value," Daniel Larremore and colleagues write. Because SARS-CoV-2 can spread from individuals with pre-symptomatic, symptomatic, and asymptomatic infections, diagnosis and isolation based on symptoms alone won't prevent spread. Rather, robust population screening, for which virus testing is often central, will be critical. However, related surveillance testing programs must make concrete choices, including: What are the tradeoffs between cost, frequency, test sensitivity, and the speed with which diagnoses can be returned? To evaluate this, Larremore and colleagues modeled how changing viral load (different levels of infectiousness) impacted the ability of an assay, or test, to diagnose infection. They calculated what percentage of these people's total infectiousness would be removed by screening and isolation, using different testing approaches. They also evaluated the impact of surveillance at the population level using two epidemiological models that incorporated viral load dynamics, one of which mimicked aspects of the contact structure of New York City. Across their analyses of individuals and populations, the inclusion of viral load in surveillance modeling revealed that the limits in detection abilities of tests mattered less than previously thought, the authors say. But delays in returning diagnoses were highly impactful, with even one-day delays between sample and answer undercutting otherwise impactful surveillance plans. As well, the frequency of surveillance testing plays a crucial role, the authors say. They note that communities vary in their transmission dynamics, so specific strategies for successful population screening will depend on the current community infection prevalence and transmission rate in a given location. They also identify other limitations in their study. Still, they say their findings could aid some groups planning societal reopening, refocusing their efforts on rapid turnaround times instead of highly sensitive tests. They may also inform regulatory agencies and test manufacturers about the importance of developing and approving such tests, optimized for surveillance (as opposed to clinical diagnosis).

As COVID toll among Kenyan doctors jumps, one widow shares her grief

Baz Ratner and Maggie Fick
Thu, 19 November 2020, 

A Funeral for Doctor Alushula who died of COVID-19 in Khumusalaba village

By Baz Ratner and Maggie Fick

KHUMUSALABA, Kenya (Reuters) - When Daniel Alushula began gasping for air after contracting COVID-19 last month, all the intensive care beds in his home town hospital were taken and he had to travel around 50 km (30 miles) to secure one.

The 60-year-old orthopedic surgeon died a week later on Oct. 30, his family said, one of nine Kenyan doctors to have succumbed to the virus in the past four weeks, according to the Kenya Medical Practitioners, Pharmacists and Dentists Union.

He was active in the union's campaign to better protect doctors and their families from the risk of catching while at work, fellow medic Anthony Akoto said.

Four of the nine doctors who have fallen victim to the pandemic died over the past weekend, and the Union has threatened a national strike from Dec. 6 if the government fails to provide protective equipment and medical insurance for its members, and compensation for health workers who die from COVID-19.

"We are not going to be sacrificial lambs," its secretary-general, Chibanzi Mwachonda, told Reuters.

The Health Ministry did not respond to requests for comment.

Up to mid-October, COVID-19 had killed just one Kenyan doctor, as travel restrictions and mandatory mask wearing spared the country the worst of its first wave.

However, the disease has spread faster in the general population too since the government eased the curbs in late September, with compliance with mask wearing and social distancing also dropping.

As of Wednesday, the country had reported 1,313 deaths, about a quarter of which have occurred in November, and hospital beds are filling up across the country.

Before he died, Alushula tried to keep his colleagues' spirits up.

"No need to panic, daktari", Alushula wrote in a text message from his ICU bed to Akoto, a younger doctor he mentored at the hospital in the western district of Busia where they both worked. "You take care of the others, but I will pull through."

Akoto said Alushula's health insurance as a public doctor did not cover his COVID treatment, which his family had to pay for his treatment themselves. His wife and two children were also infected but recovered.

Alushula had not been treating COVID patients, his colleagues said, and it was unclear how he was infected.

At his funeral on Saturday, his wife Carolyne Alushula recalled his dedication. If he was called to an emergency while they were out in the car, she would often take a bus home so that he could drive a sick person to hospital.

"He treasured his calling more than anything else," she said.

(Reporting by Baz Ratner in Khumasalaba, Kenya and Maggie Fick; Editing by Katharine Houreld and John Stonestreet)

Covid-19 mink variants discovered in humans in seven countries

Denmark has already launched a nationwide cull of its farmed mink herd after concerns for vaccine efficacy

Danish farmers have until midnight on Thursday 19 November to cull all mink in the country. Photograph: Mads Claus Rasmussen/Ritzau Scanpix/AFP/Getty

Animals farmed is supported by
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Sophie Kevany and Tom Carstensen
Wed 18 Nov 2020 

Seven countries are now reporting mink-related Sars-CoV-2 mutations in humans, according to new scientific analysis.

The mutations are identified as Covid-19 mink variants as they have repeatedly been found in mink and now in humans as well.

Uncertainty around the implications of the discovery of a Covid-19 mink variant in humans led Denmark, the world’s largest mink fur producer, to launch a nationwide cull earlier this month.

The cull was sparked by research from Denmark’s public health body, the Statens Serum Institut (SSI), which showed that a mink variant called C5 was harder for antibodies to neutralise and posed a potential threat to vaccine efficacy.

Denmark, the Netherlands, South Africa, Switzerland, the Faroe Islands, Russia and the US have all reported cases of mink-related mutations.

Despite a political backlash the cull has continued, and farmers have until midnight on Thursday to cull all mink in the country. However, the row over the cull has forced the resignation of the Danish agriculture minister, Mogens Jensen.

SSI director Kåre Mølbak has also said he would resign. It was the SSI’s findings on reduced antibody efficacy that led to the cull order. Mølbak told local media he is retiring because he is 65 and denied it was related to the mink cull.

Until now there had been no widespread reports of mink variants in humans outside Denmark. But scientists uploading virus sequencing and variant information to Gisaid, a global database initiative, said there have been signs of the mink variants around the world.

“We knew there were these mink variants in seven countries, but we only had about 20 genomes of each, which is very few. Then last week the Danes uploaded 6,000 genome sequences and with those we were able to identify 300 or more of the mink variant Y453F in viruses having infected humans in Denmark,” said University College London (UCL) Genetics Institute director Francois Balloux.

Asked about the implications of the findings, Balloux said it was an indication of the need to cull farmed mink. “A bigger host reservoir means more infections in humans. The main point here, I think, is that although the mutation might not be scary, there is still very good reason to get rid of the mink reservoir. We just don’t need it.” In Denmark, he added, they have a lot of mink, “over three times more than humans”.


Denmark's mass mink cull illegal, PM admits as opposition mounts
Read more

The prevalence of Danish mink-related mutations is evident in the Gisaid database. “Denmark has 329 F-variant sequences, which roughly maps to as many individuals, although there may be some duplicates,” said Prof Seshadri Vasan, who leads the dangerous pathogens team at Australia’s Commonwealth Scientific and Industrial Research Organisation (CSIRO) and analysed the database for the mink variants. “The Netherlands has six. South Africa and Switzerland have two each, while the Faroe Islands, Russia and Utah [US] have one each.”

Asked how the spread might have happened, Vasan said that given some of the human and mink F-variants were from samples collected in Denmark in June, it might be that “movement of people, animals or goods could have spread the F-variant to other countries”.

But, because the Gisaid database includes only patchy patient information and no travel history – and as some of the samples lack collection dates – he said it is impossible to say exactly how and when the spread took place, although local scientists might be better placed to understand.

Last month, Vasan and his team published a global template aimed at improving the collection and sharing of de-identified patient information in a bid to improve data quality.

Viruses are known to mutate, but variants alone are not necessarily a problem. Most importantly, said Prof Joanne Santini, a microbiologist at UCL, we still don’t know whether this mutation happened in mink or humans first.

In a joint email this week to the Guardian, Santini and UCL colleague Prof Sarah Edwards, a bioethicist, said the Sars-CoV-2 Y453F variant in the spike protein is “unlikely to pose any serious risk to the expected efficacy of current candidate vaccines, or itself pose a new public health threat” on its own.

If, however, the variant originated in mink and spread to humans, “then we would have to doubt our ability to manage outbreaks in otherwise seemingly contained farm animals once detected”.

Constant mutations could be a source of concern too. The email added that “multiple additional variants in the spike protein could indeed have concerning implications for how infectious the virus is to humans and also to animals”, potentially posing “new threats to the expected efficacy of our candidate vaccines”.

“The early observations by CSIRO scientists demonstrate the possible implications for the wider spread of Sars-CoV-2 variants between humans and animals,” she said.

Although Denmark is the only country to order a nationwide mink cull, others, including the Netherlands, Spain and, most recently, Greece, are killing mink with Covid-19. On Tuesday, Reuters reported mandatory mink testing had started in Poland, despite industry fears that tests could lead to a nationwide cull.

On the business side, the Danish cull has had immediate effects. Last week, Denmark’s breeder association and world’s largest fur auction house, Kopenhagen Fur, announced a “controlled shutdown” over the next three years, while Danish thinktank estimates put the cost of mink farm closures at about DKK3bn (£360m).

Two K-State studies focus on SARS-CoV-2 transmission in domestic cats, pigs

KANSAS STATE UNIVERSITY

Research News

 

IMAGE: JÜRGEN A. RICHT, THE REGENTS DISTINGUISHED PROFESSOR AT KANSAS STATE UNIVERSITY IN THE COLLEGE OF VETERINARY MEDICINE, IS THE SENIOR AUTHOR ON TWO RECENTLY PUBLISHED STUDIES THAT FOCUS ON SARS-COV-2... view more 

CREDIT: KANSAS STATE UNIVERSITY

MANHATTAN, KANSAS -- Two recently published studies from Kansas State University researchers and collaborators have led to two important findings related to the COVID-19 pandemic: Domestic cats can be asymptomatic carriers of SARS-CoV-2, but pigs are unlikely to be significant carriers of the virus. SARS-CoV-2 is the coronavirus responsible for COVID-19.

"Other research has shown that COVID-19-infected human patients are transmitting SARS-CoV-2 to cats; this includes domestic cats and even large cats, such as lions and tigers," said Jürgen A. Richt, the Regents distinguished professor at Kansas State University in the College of Veterinary Medicine. "Our findings are important because of the close association between humans and companion animals."

There are about 95 million house cats in the U.S. and about 60 million to 100 million feral cats, Richt said.

Richt is the senior author on the two recent collaborative publications in the journal Emerging Microbes & Infections: "SARS-CoV-2 infection, disease and transmission in domestic cats" and "Susceptibility of swine cells and domestic pigs to SARS-CoV-2."

Through their in-depth study at the K-State Biosecurity Research Institute, or BRI, at Pat Roberts Hall, the researchers studied susceptibility to infection, disease and transmission in domestic cats. They found that domestic cats may not have obvious clinical signs of SARS-CoV-2, but they still shed the virus through their nasal, oral and rectal cavities and can spread it efficiently to other cats within two days. Further research is needed to study whether domestic cats can spread the virus to other animals and humans.

"This efficient transmission between domestic cats indicates a significant animal and public health need to investigate a potential human-cat-human transmission chain," said Richt, who is also the director of the university's Center of Excellence for Emerging and Zoonotic Animal Diseases, known as CEEZAD, and the Center on Emerging and Zoonotic Infectious Diseases, known as CEZID.

For the study involving pigs, the researchers found that SARS-CoV-2-infected pigs are not susceptible to SARS-CoV-2 infection and do not appear to transmit the virus to contact animals.

"Pigs play an important role in U.S. agriculture, which made it important to determine the potential SARS-CoV-2 susceptibility in pigs," Richt said. "Our results show that pigs are unlikely to be significant carriers of SARS-CoV-2."

The BRI has provided the high-security laboratories for Richt and collaborators to study SARS-CoV-2. It is a biosafety level-3 and biosafety level-3 agriculture facility that houses important multidisciplinary research, training and educational programs on pathogens that affect animals, plants and insects, as well as food safety and security.

Richt and his collaborators plan further studies to understand SARS-CoV-2 transmission in cats and pigs. They also plan to study whether cats are immune to SARS-CoV-2 reinfection after they have recovered from a primary SARS-CoV-2 infection.

"This research is important for risk assessment, implementing mitigation strategies, addressing animal welfare issues, and to develop preclinical animal models for evaluating drug and vaccine candidates for COVID-19," Richt said.

###

The research has involved other K-State researchers from the department of diagnostic medicine and pathobiology in the College of Veterinary Medicine: Natasha N. Gaudreault, Jessie D. Trujillo, David A. Meekins, Igor Morozov, Daniel W. Madden, Sabarish V. Indran, Dashzeveg Bold, Velmurugan Balaraman, Taeyong Kwon, Bianca L. Artiaga, Konner Cool, Wenjun Ma and Jamie Henningson, also director of the Kansas State Veterinary Diagnostic Laboratory.

Other researchers involved include Mariano Carossino and Udeni B. R. Balasuriya from Louisiana State University; William C. Wilson with the U.S, Department of Agriculture's Arthropod-Borne Animal Disease Research Unit; Adolfo García-Sastre with Icahn School of Medicine at Mount Sinai; and Heinz Feldmann with the National Institutes of Health's National Institute of Allergy and Infectious Diseases.

Getting it just right - the Goldilocks model of cancer

DUKE-NUS MEDICAL SCHOOL

Research News

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IMAGE: WNT SIGNALLING DAMPENS RAS-MAPK SIGNALLING, ENABLING CANCER CELLS TO GROW STEADILY INSTEAD OF HEADING TOWARDS THE PREMATURE AGEING THAT CAN BE CAUSED BY EXCESSIVE RAS-MAPK SIGNALLING. WHEN RESEARCHERS INHIBITED WNT... view more 

CREDIT: DUKE-NUS MEDICAL SCHOOL

SINGAPORE, 20 November 2020 - Sometimes, too much of a good thing can turn out to be bad. This is certainly the case for the excessive cell growth found in cancer. But when cancers try to grow too fast, this excessive speed can cause a type of cellular ageing that actually results in arrested growth. Scientists at Duke-NUS Medical School have now discovered that a well-known signalling pathway helps cancers grow by blocking the pro-growth signals from a second major cancer pathway.

Inhibiting Wnt signalling with ETC-159 reactivates the hyperactive RAS-MAPK pathway, causing cells to led undergo senescence.Many cancers are driven by activating mutations in the RAS-MAPK signalling pathway which triggers a cascade of proteins that directs cells to grow, divide and migrate. Mutations in proteins involved in this cascade can turn on genes that make this process go into overdrive, causing cells to grow out of control and aggressively invade other parts of the body. However, too much RAS-MAPK signalling causes cancer cells to prematurely age, and eventually stop growing -- a process called cellular senescence.

Publishing in Cancer Research, the Duke-NUS research team found that another important and well-known biochemical pathway, the 'Wnt' (pronounced 'wint') signalling pathway, allows some cancers to grow by dampening RAS-MAPK signalling.

The team made the discovery while investigating how Wnt proteins regulate pancreatic cancers. Scientists have long observed that genetic mutations causing Wnt proteins to be hyperactive drive many common cancers. The long-held thinking had been that this is because Wnt signalling causes cells to grow too fast. The new findings suggest this idea needs re-evaluation.

By making RAS-MAPK signalling "not too hot and not too cold", Wnt signalling enables cancers to grow steadily instead of heading towards the premature ageing that can be caused by excessive RAS-MAPK signalling. These findings support a growing awareness that cancers need a "just-right" level of RAS-MAPK signalling. Disrupting modulating signals like Wnt can cause cancers to stop growing by forcing them to undergo cellular senescence, similar to just getting old.

Assistant Professor Babita Madan, from Duke-NUS Cancer and Stem Cell Biology (CSCB) Programme, a senior co-author of the study, explained, "Using an experimental drug, ETC-159 , to stop Wnts in multiple models of human pancreatic and colorectal cancer, we found that, unexpectedly, Wnt signalling turns off as many genes as it turns on."

Digging deeper, the team made the connection between Wnt signalling and the diminished activity of the RAS-MAPK pathway. Inhibiting Wnt signalling with ETC-159 and other anti-cancer drugs actually activated RAS-MAPK signalling, while inhibiting cancer growth at the same time.

"This makes sense; while activating mutations in the RAS-MAPK pathway are common in cancer, in isolation, they cause cells to stop growing by causing senescence, a form of ageing-induced arrested cell growth," said Professor David Virshup, Director of the CSCB Programme, and also a senior co-author of the study. (Prof Virshup's seminal research on Wnts led to the development of ETC-159.) "By reining in RAS-MAPK signalling, Wnt signalling achieves Goldilocks' goal of getting it not too hot, not too cold, but just right."

One implication of this research is that it opens up additional ways to attack cancers. The traditional way is to kill cancer cells, however this new study shows that stopping cancer cell growth can be achieved by inducing senescence.

"Cancer is the second leading cause of death globally, responsible for an estimated one in six deaths. In Singapore, cancer cases have been rising over the years, and the number of people living with cancer will continue to increase ," noted Professor Patrick Casey, Senior Vice Dean for Research at Duke-NUS. "Studies like these exemplify the importance of robust fundamental science research to guide new approaches and strategies that have the potential to make a major impact on disease."

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Breast cancer discovery could help stop disease's deadly spread

UNIVERSITY OF VIRGINIA HEALTH SYSTEM

Research News

 

IMAGE: UVA'S SANCHITA BHATNAGAR, PHD, FOUND THAT THE BREAST CANCER ONCOGENE TRIM37 NOT ONLY CAUSES TRIPLE NEGATIVE BREAST CANCER TO SPREAD BUT ALSO MAKES IT RESISTANT TO CHEMOTHERAPY. view more 

CREDIT: DAN ADDISON | UVA COMMUNICATIONS

University of Virginia Cancer Center researchers have identified a gene responsible for the spread of triple-negative breast cancer to other parts of the body - a process called metastasis - and developed a potential way to stop it.

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that accounts for 40,000 deaths in the United States annually. The majority of these deaths result from resistance to chemotherapy and subsequent aggressive metastases. So UVA researchers asked: What causes a primary tumor to become metastatic? This is an important question in cancer biology because patients with metastatic tumors have the highest death rate.

UVA's Sanchita Bhatnagar, PhD, and her team found that the breast cancer oncogene TRIM37 not only causes the cancer to spread but also makes it resistant to chemotherapy. A new approach she and her colleagues have developed could possibly address both, the researchers hope.

"Despite metastasis being the key reason for failure of cancer therapies, it remains poorly understood. We do not clearly understand what drives the metastatic growth in patients," said Bhatnagar, who was the first to identify TRIM37 as a breast cancer oncogene. "In general, several genes are altered during tumorigenesis. However, whether targeting the same genes will prevent metastatic transition remains to be addressed."

Promising research from Bhatnagar's team shows that targeting TRIM37 prevents metastatic lesions in mouse models. Those findings form the foundation of her lab's current work exploring the role of TRIM37 in racial disparities in triple negative breast cancer. Incidence of the disease is disproportionately higher in African-American women compared with other races, with a 5-year survival rate in African-American patients of only 14% compared with 36% in non-African-American women.

Targeting Triple-Negative Breast Cancer

Bhatnagar and UVA's Jogender Tushir-Singh, PhD, have developed a new approach to stop the effects of TRIM37 and, hopefully, prevent or significantly delay the spread of triple-negative breast cancer. This could also lower the disease's defenses against chemotherapy.

Blocking the gene could benefit approximately 80% of triple negative breast cancer patients, the researchers estimate.

Bhatnagar and Tushir-Singh's approach uses nanoparticles - microscopic balls of fat - to deliver treatment to block TRIM37. These nanoparticles are paired with specially engineered antibodies that bind to the cancerous cells but not to healthy cells. "As soon as the antibody finds the triple negative breast cancer cell, it binds to the receptor and is taken up by the cell," explained Tushir-Singh, of UVA's Department of Biochemistry and Molecular Genetics.

"It is a kiss of death," Bhatnagar said, "that selectively reduces the expression of TRIM37 in cancer cells and prevents the spread."

The approach could be used to deliver targeted treatments for many other cancers as well, the researchers report. "That would not only get the treatment where it needs to be but, hopefully, help prevent unwanted side effects. Besides preventing metastases, it adds selectivity," Bhatnagar said.

"A problem in the field is, how will you give [a nanoparticle treatment] to the patients? Most of these nanoparticles are cleared by the liver, so they never have a chance to really do their job," she said. "In this study, researchers bypassed this issue by delivering nanoparticles by nasal route, increasing the rate of uptake in the lungs - one of the most common metastatic target sites in TNBC patients."

The development of the new approach is in its early stages, but tests with lab mice have offered encouraging indications. "The lungs showed dramatic reduction in metastatic lesions after the treatment in comparison to the mice that received no treatment," Bhatnagar said.

Next Steps

To verify that TRIM37 targeting might offer a potential treatment approach, Bhatnagar teamed up with Tushir-Singh, her husband, to test it in the lab. "And we find that our targeted nanoparticles significantly reduce metastatic lesions in the lungs of spontaneous metastatic murine [mouse] models - both immune compromised and immune sufficient," she said. "This is an important proof-of-concept much needed for the bench-to-clinic transition of these important findings."

Clinically, most women in the early stages of breast cancer are treated with surgery, followed by radiation or chemotherapy. However, metastasis remains a challenging medical problem. Bhatnagar's research offers a potential way to target a driver of metastasis that she hopes will prevent or slow metastatic progression and improve overall survival.

Much more work needs to be done, but Bhatnagar's research is being noticed by pharmaceutical companies interested in exploring the approach's potential. "This is a delivery platform, not only for targeting our protein of interest but for many other chemotherapeutic drugs that can be packaged into the nanoparticles and selectively delivered," Bhatnagar said.

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Findings Published

The researchers have published their findings in the scientific journal Cancer Research. The research team consisted of Piotr Przanowski, Song Lou, Rachisan Djiake Tihagam, Tanmoy Mondal, Caroline Conlan, Gururaj Shivange, Ilyas Saltani, Chandrajeet Singh, Kun Xing, Benjamin B. Morris, Marty W. Mayo, Luis Teixeira, Jacqueline Lehmann-Che, Jogender Tushir-Singh and Sanchita Bhatnagar.

Bhatnagar, a Hartwell Investigator, is supported by the Department of Defense Breast Cancer Research Breakthrough Award (BC170197P1, BC190343P1) and Metavivor Translational Research Award. A provisional patent has been filed for the molecularly targeted nanoparticle design engineered by the Bhatnagar and Tushir-Singh laboratories.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at http://makingofmedicine.virginia.edu.

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Glyphosate may affect human gut microbiota

UNIVERSITY OF TURKU

Research News

 

IMAGE: IN GLYPHOSATE-SENSITIVE BACTERIA, THE EPSPS ENZYME IN THE SHIKIMATE PATHWAY IS BLOCKED BY GLYPHOSATE AND THE ESSENTIAL AROMATIC AMINO ACIDS ARE NOT PRODUCED. GLYPHOSATE-RESISTANT BACTERIA ARE NOT AFFECTED BY THE... view more 

CREDIT: PERE PUIGBÒ

Glyphosate is the most commonly used broad-spectrum herbicide. Researchers from the University of Turku in Finland have developed a new bioinformatics tool to predict if a microbe, e.g. a human gut bacterium, is sensitive to glyphosate.

"Glyphosate targets an enzyme called EPSPS in the shikimate pathway. This enzyme is crucial to synthesizing three essential amino acids. Based on the structure of the EPSPS enzyme, we are able to classify 80-90% of microbial species into sensitive or resistant to glyphosate," says Docent Pere Puigbò, developer of the new bioinformatics tool.

Based on the analyses using the new bioinformatics tool, 54% of the human core gut bacterial species are potentially sensitive to glyphosate.

"This groundbreaking study provides tools for further studies to determine the actual impact of glyphosate on human and animal gut microbiota and thus to their health," explains Docent Marjo Helander.

Glyphosate is thought to be safe to use because shikimate pathway is found only in plants, fungi and bacteria. However, glyphosate may have a strong impact on bacterial species in the human microbiome, and several recent studies have shown that perturbations in the human gut microbiome are connected to many diseases. Therefore, the widespread use of glyphosate may have a strong effect on gut microbiomes as well as on human health.

The dominance of this herbicide in the pesticide market is mainly attributed to the use of transgenic crops, such as soy, corn and canola, which are often grown as glyphosate-resistant varieties outside Europe. In Europe, glyphosate is commonly used to desiccate cereal, bean and seed crops before harvest. It is also used to eradicate weeds prior to sowing in no-till cropping systems.

The risk to come across glyphosate residue in food that has been grown in Finland is small, because desiccation of the cereal fields by glyphosate is not allowed in Finland.

A rich and diverse microbial community is living in soil, on plant surfaces, and in animal guts. It is possible that even low glyphosate residue may indirectly affect pest and pathogen occurrence in these communities.

"In addition to bioinformatics, we need experimental research to study the effects of glyphosate on microbial communities in variable environments," Helander adds.

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Gut immune cells may help send MS into remission

UNIVERSITY OF CALIFORNIA - SAN FRANCISCO

Research News

 

An international research team led by UCSF scientists has shown, for the first time, that gut immune cells travel to the brain during multiple sclerosis (MS) flare-ups in patients. These gut cells seem to be playing a protective role, helping drive MS symptoms back into remission.

Scientists know that in MS, other types of immune cells go haywire and attack myelin, crucial insulation material that helps nerve cells communicate with one another quickly and reliably. The resulting damage leads to periodic MS attacks that can leave patients struggling with vision loss, memory problems, pain and other symptoms. These "relapse" symptoms often subside on their own after days or weeks, but medical experts still don't have a good understanding of what flips the switch from flare-up to remission and back again.

The new findings, published November 20, 2020 in Science Immunology, suggest that an unexpected new player might help bring flare-ups under control: immune cells from the gut that express a type of antibody called IgA. In the gut, these cells serve as a critical first line of defense against foreign invaders and, scientists think, help keep the teeming bacteria of our gut microbiome from growing out of control. Recently, a UCSF-led international research team made the surprising discovery that, in animal models of MS, these gut immune cells leave the digestive system and travel to the brain where they appear to help cut inflammation.

"It was a very new idea," said Sergio Baranzini, PhD, a professor of neurology and member of the UCSF Weill Institute for Neurosciences, lead author on the new study. "Nobody thought to look for this type of immune cell."

Now the team, including scientists in Canada, Germany, Sweden and Switzerland, has gone a step further, finding traces of the IgA antibody in the cerebrospinal fluid of MS patients during flare-ups, but not when episodes are in remission. They also found signs of IgA-producing immune cells in donated postmortem brain tissue that had been damaged during MS attacks. The findings confirm for the first time that gut immune cells are involved in MS relapses in humans.

"Only at the time of an attack was there an increase in these cells and the antibodies they produce," Baranzini said. "That really caught our attention."

In the hopes of determining what these gut immune cells were doing in the brain, the team then looked to see what kinds of molecules the IgA antibody reacted to. Recent research has provided evidence that an unhealthy gut microbiome plays a role in MS, when certain potentially damaging species of bacteria proliferate. While the team found that IgA did not bind to myelin protein, it did bind to some of these harmful bacteria species, suggesting that, unlike other immune cells, which are known to cause damage in MS, IgA-expressing immune cells play a protective role, possibly chasing these harmful bacteria to the brain and mounting a defense against them there.

"This opens up a whole new line of research," said Anne-Katrin Pröbstel, MD, a former UCSF postdoctoral researcher, now at the University of Basel in Switzerland and first author on the paper. "I think it has huge potential for therapeutics."

Collaborations within the UCSF Benioff Center for Microbiome Medicine allowed researchers to work with the various bacteria thought to be hallmarks of the MS microbiome, and the work relied heavily on data and biological samples collected through the multidisciplinary UCSF EPIC Study, which has followed hundreds of MS patients over 16 years.

"I think UCSF is one of the only places where we could have done this, because of the access to patient samples that allow us to look at bacteria in the gut, immune cells from the blood, immune cells from the spinal fluid and brain tissue," said Pröbstel. "It's really a unique resource."

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See study online for a full list of authors, funding information, and relevant disclosures.

About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes UCSF Health, which comprises three top-ranked hospitals, as well as affiliations throughout the Bay Area. Learn more at ucsf.edu, or see our Fact Sheet.

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Gut-brain axis influences multiple sclerosis

UNIVERSITY OF BASEL

Research News

 

A Basel-led international research team has discovered a connection between the intestinal flora and sites of inflammation in the central nervous system in multiple sclerosis. A specific class of immune cell plays a central role in this newly identified gut-brain axis. The discovery could pave the way for new treatments for MS that target the intestinal flora.

What do you do when your own immune system attacks your nervous system? Newer treatments for the autoimmune disease multiple sclerosis (MS) rely on removing specific immune cells (B cells) from the blood of patients. However, researchers at both the University of Basel and the University Hospital Basel discovered several years ago that it's better not to remove too broad a range of B cells, as this can aggravate the disease.

A new study in the journal Science Immunology sheds more light on this observation: an international team of researchers, led by Dr. Anne-Katrin Pröbstel at the University of Basel and University Hospital Basel, has discovered that specific B cells form a kind of bridge between the intestinal flora and the sites of inflammation in the central nervous system, exerting an anti-inflammatory effect.

"We knew from earlier studies that the composition of intestinal flora plays a role in MS. But how exactly intestinal bacteria and immune cells influence one another was previously unknown," explains Pröbstel, the study's lead author.

Immune cells for gut and brain

At the heart of the new study are IgA-producing B cells, or IgA B cells in short. Immunoglobulin A (IgA) is a class of antibodies that specializes in immune defense of mucous membranes; the IgA B cells are key to intestinal health.

By analyzing stool samples from MS patients and healthy people, the researchers discovered that MS patients have IgA B cells in their intestines that target in particular bacteria typical of MS - i.e. bacteria that are more common in MS sufferers.

In a next step, the researchers analyzed the role of these immune cells during acute flares of the illness in a total of 56 MS patients. They found that IgA B cells accumulated in the cerebrospinal fluid and brain tissue of MS patients with acute sites of inflammation. "Apparently, these immune cells migrate from the intestine to the inflammation sites in the central nervous system, where they release an anti-inflammatory messenger substance," says Pröbstel. "That could explain why the illness worsens if these immune cells are removed from the blood with medication."

Trigger still unknown

What exactly activates the IgA B cells as helpers against MS and triggers their migration from the intestine to the central nervous system is still being investigated. "If we find the trigger for that, we could use it to treat MS," says Pröbstel. For example, it may be conceivable to change the composition of the intestinal flora of MS sufferers in a targeted way in order to mobilize IgA B cells as helpers against inflammation in the nervous system.

In addition to the University of Basel, other participants in the study included the University of California San Francisco, the Technical University of Munich, the universities of Heidelberg, Umeå (Sweden) and Toronto (Canada), and the Max Planck Institute of Colloids and Interfaces in Potsdam. The study was funded among others by the National Multiple Sclerosis Society and the Swiss National Science Foundation.

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