Tag Archives: Pandemic

Low-cost, universal oral COVID-19 vaccine prevents severe respiratory illness in hamsters

A UCLA-led team has developed an inexpensive, universal oral COVID-19 vaccine that prevented severe respiratory illness and weight loss when tested in hamsters, which are naturally susceptible to SARS-CoV-2. It proved as effective as vaccines administered by injection or intranasally in the research.

If ultimately approved for human use, it could be a weapon against all COVID-19 variants and boost uptake, particularly in low- and middle-income countries, and among those with an aversion to needles.

The study is published in the peer-reviewed journal Microbiology Spectrum.

The oral vaccine is based primarily on the nucleocapsid protein, which is the most abundantly expressed of the virus’s four major structural proteins and evolves at a much slower rate than the frequently mutating spike protein. The vaccine utilizes a highly weakened bacterium to produce the nucleocapsid protein in infected cells as well as the membrane protein, which is another highly abundant viral structural protein.

Being a universal vaccine based primarily upon the nucleocapsid protein, the vaccine is resistant to the incessant mutations of the SARS-CoV-2 spike protein upon which virtually all current vaccines are based. As a result, current vaccines rapidly become obsolete, requiring that they repeatedly be re-engineered. Hence, our vaccine should protect against new and emerging variants of SARS-CoV-2.”

Dr. Marcus Horwitz, senior author, distinguished professor of medicine in the Division of Infectious Diseases and of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA

Oral delivery also makes it easier to distribute the vaccine in resource poor areas of the world by eliminating the need for needles, syringes, and trained personnel to deliver injectable vaccines, he added. “An oral vaccine may also be attractive to many people with vaccine hesitancy on account of fear of needles.”

The researchers noted that while it worked exceptionally well in preventing severe respiratory illness, it did not provide full protection against high viral loads in the hamsters. Also, they did not test it against the Omicron strain, which contains a nearly identical nucleocapsid protein, because of this strain’s low virulence in the golden Syrian hamsters they used.

But the vaccine, they write, “is efficacious when administered via the oral route against COVID-19-like disease in a highly demanding animal model. This conveniently administered, easily manufactured, inexpensive, and readily stored and transported vaccine could play a major role in ending the COVID-19 pandemic by protecting immunized individuals from serious disease from current and future strains of SARS-CoV-2.”

The next step in the process will be to manufacture the vaccine for oral administration via an acid-resistant enteric capsule that will allow the vaccine to be safely released in the small intestine, Horwitz said. It will then be tested for safety, immunogenicity, and efficacy in humans.

“We also plan to expand the vaccine to protect against infections caused by other types of potentially pandemic coronaviruses such as the virus that causes Middle Eastern Respiratory Syndrome (MERS),” he added.

Additional authors are Qingmei Jia and Saša Masleša-Galić of UCLA; Helle Bielefeldt-Ohmann of the University of Queensland, Australia; and Rachel Maison, Airn Hartwig, and Richard Bowen of Colorado State University.

This study was supported by a Corona Virus Seed grant from the UCLA AIDS Institute and Charity Treks and by the National Institutes of Health (AI141390).

Journal reference:

Jia, Q., et al. (2023). Oral Administration of Universal Bacterium-Vectored Nucleocapsid-Expressing COVID-19 Vaccine is Efficacious in Hamsters. Microbiology Spectrum. doi.org/10.1128/spectrum.05035-22.

Co-infection with MRSA ‘superbug’ could make COVID-19 outcomes even more deadly

Global data shows nearly 10 per cent of severe COVID-19 cases involve a secondary bacterial co-infection – with Staphylococcus aureus, also known as Staph A., being the most common organism responsible for co-existing infections with SARS-CoV-2. Researchers at Western have found if you add a ‘superbug’ – methicillin-resistant Staphylococcus aureus (MRSA) – into the mix, the COVID-19 outcome could be even more deadly.

The mystery of how and why these two pathogens, when combined, contribute to the severity of the disease remains unsolved. However, a team of Western researchers has made significant progress toward solving this “whodunit”.

New research by Mariya Goncheva, Richard M. Gibson, Ainslie C. Shouldice, Jimmy D. Dikeakos and David E. Heinrichs, has revealed that IsdA, a protein found in all strains of Staph A., enhanced SARS-CoV-2 replication by 10- to 15-fold. The findings of this study are significant and could help inform the development of new therapeutic approaches for COVID-19 patients with bacterial co-infections.

Interestingly, the study, which was recently published in iScience, also showed that SARS-CoV-2 did not affect the bacteria’s growth. This was contrary to what the researchers had initially expected.

We started with an assumption that SARS-CoV-2 and hospitalization due to COVID-19 possibly caused patients to be more susceptible to bacterial infections which eventually resulted in worse outcomes.”

Mariya Goncheva

Goncheva is a former postdoctoral associate, previously with the department of microbiology and immunology at Schulich School of Medicine & Dentistry.

Goncheva said bacterial infections are most commonly acquired in hospital settings and hospitalization increases the risk of co-infection. “Bacterial infections are one of the most significant complications of respiratory viral infections such as COVID-19 and Influenza A. Despite the use of antibiotics, 25 per cent of patients co-infected with SARS-CoV-2 and bacteria, die as a result. This is especially true for patients who are hospitalized, and even more so for those in intensive care units. We were interested in finding why this happens,” said Goncheva, lead investigator of the study.

Goncheva, currently Canada Research Chair in virology and professor of biochemistry and microbiology at the University of Victoria, studied the pathogenesis of multi-drug resistant bacteria (such as MRSA) supervised by Heinrichs, professor of microbiology and immunology at Schulich Medicine & Dentistry.

When the COVID-19 pandemic hit, she pivoted to study interactions between MRSA and SARS-CoV-2.

For this study, conducted at Western’s level 3 biocontainment lab, Imaging Pathogens for Knowledge Translation (ImPaKT), Goncheva’s work created an out-of-organism laboratory model to study the interactions between SARS-CoV-2 and MRSA, a difficult-to-treat multi-drug resistant bacteria.

“At the beginning of the pandemic, the then newly opened ImPaKT facility made it possible for us to study the interactions between live SARS-CoV-2 virus and MRSA. We were able to get these insights into molecular-level interactions due to the technology at ImPaKT,” said Heinrichs, whose lab focuses on MRSA and finding drugs to treat MRSA infections. “The next step would be to replicate this study in relevant animal models.”

Journal reference:

Goncheva, M. I., et al. (2023). The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling. IScience. doi.org/10.1016/j.isci.2023.105975.

Emergence of extensively drug-resistant Shigella sonnei strain in France

Shigellosis, a highly contagious diarrheal disease, is caused by Shigella bacteria circulating in industrializing countries but also in industrialized countries. Scientists from the French National Reference Center for Escherichia coli, Shigella and Salmonella at the Institut Pasteur who have been monitoring Shigella in France for several years have detected the emergence of extensively drug-resistant (XDR) strains of Shigella sonnei. Bacterial genome sequencing and case characteristics (with most cases being reported in male adults) suggest that these strains, which originated in South Asia, mainly spread among men who have sex with men (MSM). This observation needs to be taken into account by clinicians and laboratories when testing for sexually transmitted infections (STIs) in MSM, and systematic antibiograms should be performed if a Shigella strain is isolated to improve treatment for patients infected with XDR strains. The results were published in the journal Nature Communications on January 26, 2023.

Shigellosis is a highly contagious diarrheal disease that spreads through fecal-oral transmission. Among the different types of Shigella, Shigella sonnei is the species that mainly circulates in industrialized countries. Shigella sonnei infections can cause short-term diarrhea (3-4 days) that resolves on its own. Antibiotic treatment is, however, necessary for moderate to severe cases (bloody diarrhea, risk of complications) or to prevent person-to-person transmission in epidemic situations. The acquisition of antibiotic resistance mechanisms by Shigella bacteria therefore restricts therapeutic options.

In this study, scientists from the National Reference Center for Escherichia coli, Shigella and Salmonella (CNR-ESS) at the Institut Pasteur demonstrate an increase in antibiotic resistance in S. sonnei isolates collected in France over the past 17 years. The study is based on an analysis of more than 7,000 S. sonnei isolates and epidemiological information gathered in connection with national shigellosis surveillance conducted by the CNR-ESS between 2005 and 2021. The CNR-ESS analyzes all the bacterial isolates sent by its network of private and public partner laboratories throughout France. Over this period, isolates described as “extensively drug resistant” (XDR) were identified for the first time in 2015. The scientists then observed that the proportion of XDR isolates, which are resistant to virtually all the antibiotics recommended for treating shigellosis, increased significantly and reached a peak in 2021, when 22.3% of all S. sonnei isolates (99 cases) were XDR.

Genome sequencing revealed that all these French XDR strains belonged to the same evolutionary lineage, which became resistant to a key antibiotic (ciprofloxacin) in around 2007 in South Asia. In several geographical regions of the world, including France, the strains then acquired different plasmids coding for resistance to other first-line antibiotics (especially third-generation cephalosporins and azithromycin). For severe cases, the only antibiotics that are still effective are carbapenems or colistin, which must be administered intravenously, resulting in more aggressive treatment that requires more complex monitoring in a hospital environment.

XDR isolates were observed in France in various contexts: in travelers returning from South Asia or South-East Asia, during an outbreak at a school in 2017 (more than 90 cases, leading to school closure; the index case had returned from South-East Asia) and in men who have sex with men (MSM). The latter were infected by an epidemic clone that has been spreading throughout Europe since 2020 but has also been found in North America and Australia. This subgroup of XDR strains circulating in MSM was the most widespread, accounting for 97% of XDR strains in France in 2021.

Frequent use of antibiotics in South and South-East Asia, together with repeat treatment for STIs in some people potentially exposed to this risk, increase the likelihood of selection of XDR Shigella strains. Further research is needed to understand the different clinical forms of infection, and especially whether there are asymptomatic forms that might cause the bacteria to spread more widely. Therapeutic trials are also crucial to identify effective oral antibiotics for treating these XDR Shigella strains.

  • Sophie Lefèvre, Elisabeth Njamkepo, Sarah Feldman, Corinne Ruckly, Isabelle Carle, Monique Lejay-Collin, Laëtitia Fabre, Iman Yassine, Lise Frézal, Maria Pardos de la Gandara, Arnaud Fontanet, François-Xavier Weill. Rapid emergence of extensively drug-resistant Shigella sonnei in France. Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-36222-8
  • Institut Pasteur

    Bald eagles aren’t fledging as many chicks due to avian influenza

    Bald eagles are often touted as a massive conservation success story due to their rebound from near extinction in the 1960s.

    But now a highly infectious virus may put that hard-fought comeback in jeopardy.

    Published in Nature’s Scientific Reports, new research from the University of Georgia showed highly pathogenic avian influenza, also known as H5N1, is killing off unprecedented numbers of mating pairs of bald eagles.

    “Even just one year of losses of productivity like we’ve documented regionally is very concerning and could have effects for decades to come if representative of broader regions,” said Nicole Nemeth, lead author of the study and an associate professor in the College of Veterinary Medicine. “There were nights where I couldn’t sleep based on what we were hearing and seeing. We have already lost unprecedented numbers of wild birds due to this virus in the U.S. and it appears here to stay.”

    Less than half of Georgia bald eagle nests fledged one chick in 2022

    The researchers found that just under half of bald eagle nests along coastal Georgia successfully fledged at least one eaglet in 2022. That’s 30% below average for the region.

    The study also showed the success rate for nests was halved in one Florida county, dropping to 41% from an average of 86.5%. Another Florida county experienced a less dramatic but still concerning decrease from an average of approximately 78% to 66.7%.

    “We had reports from people who faithfully monitor eagle nests year after year with these heartbreaking stories of an adult eagle found dead below their nest. Within a few days, often its mate and the chicks were also found dead below the nest. It is clear the virus is causing nest failures,” said Nemeth, who is part of the UGA-based Southeastern Cooperative Wildlife Disease Study (SCWDS).

    The collaboration is the first diagnostic and research service established specifically to investigate wildlife diseases.

    Number of infected wild birds likely an undercount

    In April 2022, SCWDS researchers confirmed highly pathogenic avian influenza had hit Georgia’s eagle populations for the first time.

    The three dead eagles were found in Chatham, Glynn and Liberty counties in March.

    At the time, the U.S. Department of Agriculture (USDA) had confirmed around 660 cases of the H5N1 virus in wild birds, only 11 of which were from Georgia.

    That number has since skyrocketed to more than 6,200 reported cases across the country, according to the USDA’s Animal and Plant Health Inspection Service.

    Those cases include a variety of vultures and other raptors, waterfowl like geese and ducks, as well as other aquatic birds like pelicans and herons, and even some songbirds, though they are less common victims of the virus. (Tens of millions of commercially farmed poultry have died or been culled due to risk of infection.)

    “I think the number of wild bird cases is drastically underreported,” Nemeth said. “People will submit one snow goose, for example, and it will test positive for the virus. And then they’ll tell you, ‘Well, there are thousands of geese dying at the same site.’ But it only goes down as one infected bird.”

    H5N1 doesn’t pose massive threat to humans but may to other species

    The birds at biggest risk of infection are those that live in coastal or other aquatic areas inland or prey on other birds that do.

    The virus can persist in water for over a year, given the proper conditions. While not a risk to people, birds can pick up the virus from spending time in the water and carry it to new locations through migration.

    Raptors like eagles and vultures then catch the virus when they consume the infected birds.

    “Worst case scenario, we get into a scary place with some of these bird species,” Nemeth said. “We could see a lot more decline in the numbers of eagles, raptors, waterfowl and other birds than what we’ve already seen. It could be devastating.”

    Bears, red foxes and coyotes among animals infected with virus

    Avian influenza has hopped species as well.

    H5N1 has infected wild mammals such as red foxes, coyotes, racoons, seals, opossums and even some bears in North America. However, very few people have been infected with the virus in the U.S. and have recovered with minimal symptoms, according to the Centers for Disease Control and Prevention.

    “A virus that can spread and be maintained as this virus can, it’s everywhere now,” Nemeth said. “We can’t contain the virus, and we can’t vaccinate wild birds. But we can document the losses and try to help conserve affected species and populations the best we can.”

    The study was co-authored by the University of Georgia’s Mark Ruder, Rebecca Poulson and David Stallknecht. Additional co-authors include Robert Sargent of the Georgia Department of Natural Resources, Shawnlei Breeding of Audubon’s EagleWatch, Meaghan Evans, Jared Zimmerman, Rebecca Hardman, Mark Cunningham of Florida Fish and Wildlife Conservation Commission and Samantha Gibbs of U.S. Fish & Wildlife.

  • Nicole M. Nemeth, Mark G. Ruder, Rebecca L. Poulson, Robert Sargent, Shawnlei Breeding, Meaghan N. Evans, Jared Zimmerman, Rebecca Hardman, Mark Cunningham, Samantha Gibbs, David E. Stallknecht. Bald eagle mortality and nest failure due to clade highly pathogenic H5N1 influenza a virus. Scientific Reports, 2023; 13 (1) DOI: 10.1038/s41598-023-27446-1
  • University of Georgia

    The achilles heel of the influenza virus: Ubiquitin protein may be an approach for future medicines

    Influenza viruses are becoming increasingly resilient to medicines. For this reason, new active ingredients are needed. Important findings in this regard have been provided by researchers at the University of Münster: for the virus to proliferate, the polymerase of the influenza A virus has to be modified many times through enzymes in the host cells. The team of researchers was able to produce a comprehensive map of types of modification. Medicines directed against the enzymes woud be resilient to rapid mutations in the virus, thus offering great potential for the future.

    Every year, the influenza season presents a challenge to hospitals. Despite having been vaccinated, older people and patients with health problems in particular run a heightened risk of falling prey to a severe bout of influenza. What is especially insidious about influenza viruses is their ability to mutate rapidly, which makes them increasingly resilient to medicines. For this reason, there is an urgent need for new active ingredients in order to be able to continue providing effective treatment for the illness in future. Researchers at the University of Münster have taken an important step in this direction which is described in a study published in the latest issue of the journal “Nature Communications.” The team was able to provide evidence of 59 specific modifications to the polymerase of the influenza A virus, in other words the decisive enzyme responsible for the production of copies of the virus genome. What is special about the modifications described in the study is that they are transmitted by proteins in the host cells — and, in contrast to virus proteins, they cannot mutate rapidly. They therefore represent a promising approach for the production of new medicines.

    The influenza A virus polymerase (IAV polymerase) is a highly complex protein which has more than just one function. One of these is that after a structural change it can also make copies of the virus genome (cRNA and vRNA). Without this “switch” of functions, the virus is not able to proliferate. As Dr. Linda Brunotte and Dr. Franziska Günl and a team of colleagues now discovered, the IAV polymerase needs proteins from the host cell to act as “molecular switches” and carry out its diverse functions. These proteins are enzymes which dock so-called ubiquitin proteins onto specific places in the polymerase and, as a result, trigger the signal for the switch of functions. “We were able to produce a map showing 59 positions on the viral polymerase to which ubiquitin was attached through the host cell. These are completely new findings which reveal the Achilles’ heel of the influenza A virus,” explains Dr. Brunotte, who heads a team of researchers at the Institute of Molecular Virology and also initiated the study.

    This ubquitination had a definite influence on the activity of the polymerase at 17 spots. Moreover, one specific position was discovered whose modification represents the signal for the conversion and the associated switch of functions in the polymerase. As a result, Dr. Günl, the lead author of the study, is now looking ahead: “On the basis of our mapping of the ubiquitination, further studies can now research into which enzymes are specifically responsible for the modification of the IAV polymerase. Medicines which are directed against these enzymes would be resistent to mutations in influenza viruses, thus displaying great potential for future treatments.

    The study produced by Dr. Brunotte and Dr. Günl received 266,000 euros in funding from the German Research Foundation. Appropriately, the date on which the two successful researchers published their results was the International Day of Women in Science.

  • Franziska Günl, Tim Krischuns, Julian A. Schreiber, Lea Henschel, Marius Wahrenburg, Hannes C. A. Drexler, Sebastian A. Leidel, Vlad Cojocaru, Guiscard Seebohm, Alexander Mellmann, Martin Schwemmle, Stephan Ludwig, Linda Brunotte. The ubiquitination landscape of the influenza A virus polymerase. Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-36389-0
  • University of Münster

    500,000 People Miss Out on Life-Saving Drugs, Sparking a Potential Surge of Heart Attacks and Strokes

    According to a study recently published in Nature Medicine and supported by the British Heart Foundation (BHF) Data Science Centre at Health Data Research UK, approximately 500,000 individuals were unable to initiate treatment with blood pressure-lowering medications during the Covid-19 pandemic.

    The researchers warn that the delay in starting vital blood pressure-lowering medications could result in thousands of preventable heart attacks or strokes, as these medications play a crucial role in preventing deadly heart and circulatory diseases.

    Using data on routinely dispensed prescriptions in England, Scotland, and Wales, scientists found that 491,306 fewer people than expected started taking blood pressure-lowering medication between March 2020 and the end of July 2021.

    If these individuals’ high blood pressure remains untreated over their lifetime, the team estimate that this could lead to more than 13,500 additional cardiovascular events, including over 2,000 heart attacks and 3,000 strokes.

    These findings highlight an important opportunity for the NHS to identify and treat people who should have started taking medicines to reduce their risk of conditions including heart attack and stroke.

    Lead author Professor Reecha Sofat, Associate Director at the BHF Data Science Centre, Breckenridge Chair of Clinical Pharmacology at the University of Liverpool, warned:

    “Measures to prevent infection spread were necessary and undoubtedly saved lives. The NHS has already taken important and positive steps toward identifying people with high blood pressure as early as possible. However, we need this focus to be sustained in the long-term to prevent any increase in heart attacks and strokes which will add to a healthcare system already under extreme pressure.”

    To understand more about the impact of the Covid-19 pandemic on the management of risk factors for heart and circulatory diseases, the researchers analyzed 1.32 billion records of medications dispensed to 15.8 million people in England, Scotland, and Wales between 1st April 2018 and 31st July 2021.

    This showed that, by the first half of 2021, on average, 27,070 fewer people started taking blood pressure-lowering medication each month between compared with 2019. In the same period, they found that 16,744 fewer people started taking medication to reduce levels of fat or cholesterol in their blood each month.

    Identifying the individuals who missed starting medication as soon as possible will be critical to reducing their cardiovascular risk. The team believes that identifying those who missed out on blood pressure treatment within five years would reduce the total number of cardiovascular events to just over 2,700.

    This is the first time that medicines data has been used to follow changes in the day-to-day management of chronic conditions. The researchers say that being able to routinely track this in the future, particularly during healthcare crises, would allow the NHS and policymakers to step in earlier to avoid a repeat of the impact of the Covid-19 pandemic.

    Professor Sofat added: “Despite the incredible work done by NHS staff, our data show that we’re still not identifying people with cardiovascular risk factors at the same rate as we were before the pandemic. Detecting these risk factors early and beginning medication where appropriate is crucial to managing them, helping more people to avoid a preventable heart attack or stroke so they can live in good health for longer.”

    Dr. Sonya Babu-Narayan, Associate Medical Director at the British Heart Foundation and consultant cardiologist, said: “Yet again we’re seeing clear evidence of the major disruption to healthcare people in the UK experienced during the Covid-19 pandemic. But it’s not too late to limit the damage. These findings demonstrate how getting heart healthcare back on track can curb the additional strain that untreated risk factors such as high blood pressure would otherwise place on the NHS.

    She concludes, “We need to make it easier and more accessible for everyone to know their numbers – particularly their blood pressure and cholesterol. This means empowering people to access the help they need when they need it so they can be supported to manage their own health.”

    Reference: “The impact of the COVID-19 pandemic on cardiovascular disease prevention and management” by Caroline E. Dale, Rohan Takhar, Raymond Carragher, Michail Katsoulis, Fatemeh Torabi, Stephen Duffield, Seamus Kent, Tanja Mueller, Amanj Kurdi, Thu Nguyen Le Anh, Stuart McTaggart, Hoda Abbasizanjani, Sam Hollings, Andrew Scourfield, Ronan A. Lyons, Rowena Griffiths, Jane Lyons, Gareth Davies, Daniel Harris, Alex Handy, Mehrdad A. Mizani, Christopher Tomlinson, Johan H. Thygesen, Mark Ashworth, Spiros Denaxas, Amitava Banerjee, Jonathan A. C. Sterne, Paul Brown, Ian Bullard, Rouven Priedon, Mamas A. Mamas, Ann Slee, Paula Lorgelly, Munir Pirmohamed, Kamlesh Khunti, Andrew D. Morris, Cathie Sudlow, Ashley Akbari, Marion Bennie, Naveed Sattar, Reecha Sofat and CVD-COVID-UK Consortium, 19 January 2023, Nature Medicine.
    DOI: 10.1038/s41591-022-02158-7

    The British Heart Foundation Data Science Centre is part of Health Data Research UK and is funded by the British Heart Foundation.

    What is spillover? Bird flu outbreak underscores need for early detection to prevent the next big pandemic

    The current epidemic of avian influenza has killed over 58 million birds in the U.S. as of February 2023. Following on the heels of the COVID-19 pandemic, large outbreaks of viruses like bird flu raise the specter of another disease jumping from animals into humans. This process is called spillover.

    I’m a veterinarian and a researcher who studies how diseases spread between animals and people. I was on the Colorado State University veterinary diagnostic team that helped detect some of the earliest cases of H5N1 avian influenza in U.S. birds in 2022. As this year’s outbreak of bird flu grows, people are understandably worried about spillover.

    Given that the next potential pandemic will likely originate from animals, it’s important to understand how and why spillover occurs – and what can be done to stop it.

    Spillover involves any type of disease-causing pathogen, be it a virus, parasite or bacteria, jumping into humans. The pathogen can be something never before seen in people, such as a new Ebola virus carried by bats, or it could be something well known and recurring, like Salmonella from farm animals.

    The term spillover evokes images of a container of liquid overflowing, and this image is a great metaphor for how the process works.

    Imagine water being poured into a cup. If the water level keeps increasing, the water will flow over the rim, and anything nearby could get splashed. In viral spillover, the cup is an animal population, the water is a zoonotic disease capable of spreading from an animal to a person, and humans are the ones standing in the splash zone.

    The probability that a spillover will occur depends on many biological and social factors, including the rate and severity of animal infections, environmental pressure on the disease to evolve and the amount of close contact between infected animals and people.

    While not all animal viruses or other pathogens are capable of spilling over into people, up to three-quarters of all new human infectious diseases have originated from animals. There’s a good chance the next big pandemic risk will arise from spillover, and the more that’s known about how spillovers occur, the better chance there is at preventing it.

    Most spillover research today is focused on learning about and preventing viruses – including coronaviruses, like the one that causes COVID-19 and certain viral lineages of avian influenza – from jumping into humans. These viruses mutate very quickly, and random changes in their genetic code could eventually allow them to infect humans.

    Spillover events can be hard to detect, flying under the radar without leading to bigger outbreaks. Sometimes a virus that transfers from animals to humans poses no risk to people if the virus is not well adapted to human biology. But the more often this jump occurs, the higher the chances a dangerous pathogen will adapt and take off.

    Epidemiologists are projecting that the risk of spillover from wildlife into humans will increase in coming years, in large part because of the destruction of nature and encroachment of humans into previously wild places.

    Because of habitat loss, climate change and changes in land use, humanity is collectively jostling the table that is holding up that cup of water. With less stability, spillover becomes more likely as animals are stressed, crowded and on the move.

    As development expands into new habitats, wild animals come into closer contact with people – and, importantly, the food supply. The mixing of wildlife and farm animals greatly amplifies the risk that a disease will jump species and spread like wildfire among farm animals. Poultry across the U.S. are experiencing this now, thanks to a new form of avian flu that experts think spread to chicken farms mostly through migrating ducks.

    The new avian influenza virus is a distant descendant of the original H5N1 strain that has caused human epidemics of bird flu in the past. Health officials are detecting cases of this new flu virus jumping from birds to other mammals – like foxes, skunks and bears.

    On Feb. 23, 2023, news outlets began reporting a few confirmed infections of people in Cambodia, including one infection leading to the death of an 11-year-old girl. While this new strain of bird flu can infect people in rare situations, it isn’t very good at doing so, because it is not able to bind to cells in human respiratory tracts very effectively. For now, the Centers for Disease Control and Prevention thinks there is low risk to the general public.

    Active monitoring of wild animals, farm animals and humans will allow health officials to detect the first sign of spillover and help prevent a small viral splash from turning into a large outbreak. Moving forward, researchers and policymakers can take steps to prevent spillover events by preserving nature, keeping wildlife wild and separate from livestock and improving early detection of novel infections in people and animals.

    Treana Mayer

    The Conversation

    New analysis shows how convalescent plasma can be used as effective, low-cost COVID-19 treatment

    Three years into the COVID-19 pandemic, new variant outbreaks continue to fuel economic disruptions and hospitalizations across the globe. Effective therapies remain unavailable in much of the world, and circulating variants have rendered monoclonal antibody treatments ineffective. But a new analysis shows how convalescent plasma can be used as an effective and low-cost treatment both during the COVID-19 pandemic and in the inevitable pandemics of the future.

    In astudy published in Clinical Infectious Diseases, an international team of researchers analyzed clinical data and concluded that among outpatients with COVID-19, antibodies to SARS-CoV-2 given early and in high dose reduced the risk of hospitalization.

    If the results of this meta-analysis had somehow been available in March of 2020, then I am certain that millions of lives would have been saved around the world.”

    Dr. Adam C. Levine, study author, professor of emergency medicine at Brown University’s Warren Alpert Medical School

    While several other early treatments for COVID-19 have had similar results, including antivirals like Paxlovid and monoclonal antibodies, only convalescent plasma, the researchers concluded, is likely to be both available and affordable for the majority of the world’s population both now and early in the next viral pandemic.

    “These findings will be helpful for this pandemic, especially in places like China, India and other parts of the world that lack access to antiviral medications like Paxlovid,” Levine said. “And because it provides information on how to more effectively use convalescent plasma as a therapy, this will be even more helpful in the next pandemic. This study is essentially a roadmap for how to do this right the next time.”

    Blood plasma from people who have recovered from COVID-19 and contains antibodies against SARS-CoV-2 was used as a treatment early in the pandemic, Levine said -; months before monoclonal antibody treatment or vaccines became available, and more than a year before an effective oral drug therapy was clinically available.

    Although convalescent plasma seemed promising, outpatient research was limited, and studies that did exist showed mixed results. One problem was that most studies were conducted in patients already hospitalized with COVID-19, Levine said, largely due to the convenience of conducting research with this population. The objective in the new study was to review all available randomized controlled trials of convalescent plasma in non-hospitalized adults with COVID-19 to determine whether early treatment can reduce the risk of hospitalization.

    The analysis included data from five studies conducted in four countries, including Argentina, the Netherlands, Spain, and two in the United States. Levine previously supervised enrollment at Rhode Island Hospital in a clinical trial led by Johns Hopkins Medicine and Johns Hopkins Bloomberg School of Public Health. Across the five studies, a total of 2,620 adult patients had received transfusions of convalescent plasma from January 2020 to September 2022. The researchers conducted an individual participant data meta-analysis to assess how the transfusion timing and dose impacted the patient’s risk of hospitalization during the 28 days after infection.

    In their analysis, the researchers found that 160 (12.2%) of 1,315 control patients were hospitalized compared with 111 (8.5%) of 1,305 patients treated with COVID-19 convalescent plasma -; 30% fewer hospitalizations.

    Notably, the strongest effects were seen in patients treated both early in the illness and with plasma with high levels of antibodies. In these patients, the reduction in hospitalization was over 50%.

    For future pandemics, the goal is to use plasma from donors who have high levels of antibodies, said corresponding study author Dr. David J. Sullivan, a professor of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health and School of Medicine. “This research suggests that we have been underdosing convalescent plasma for many previous pathogens, which impacts effectiveness,” Sullivan said. “It bears repeating: Early and high levels of antibodies increased the beneficial efficacy.”

    Levine explained that because convalescent plasma was the only treatment available at the beginning of the pandemic, it was used widely -; and often incorrectly, on hospitalized patients who were already experiencing severe symptoms late in the course of COVID-19. Those symptoms were due to a ramped-up immune response to the virus, not the virus itself, Levine explained.

    “By the time the patient was at the point where they’d reached the inflammatory phase that caused severe symptoms, it was too late for treatments like convalescent plasma or even monoclonal antibodies to work,” he said.

    What is now known is that convalescent plasma works best when given early in the course of illness. That’s when it can neutralize the virus and get ahead of the body mounting an intense immune response, thereby preventing hospitalization and death, Levine said.

    The five drug treatment trials in the analysis took place at a variety of global health care sites, he noted, including nursing homes, outpatient clinics and emergency departments. The diversity across the studies is a sign that the data is likely generalizable to many other types of populations and settings around the world, said Levine, who also directs the Center for Human Rights and Humanitarian Studies at the Watson Institute for International and Public Affairs at Brown.

    Levine cited another recently published study in JAMA Network Open that showed that convalescent plasma is effective in reducing mortality in immunocompromised patients. This new meta-analysis provides evidence that convalescent plasma can also be effective in the larger population of adults who are not immunocompromised.

    The U.S. Food and Drug Administration allowed early convalescent plasma use in December 2021 for those patients with COVID-19 who were also immunocompromised, but not yet for patients with COVID-19 who are not immunocompromised. The authors said they hope the new study will push the FDA, and other countries around the world, to make early treatment with COVID-19 convalescent plasma available to a much larger group of patients at risk for hospitalization.

    A treatment that evolves with the pandemic

    The findings come at a time when monoclonal antibodies, the most commonly used treatment for COVID-19, have been shown to be ineffective against new variants of the virus. In November, the FDA revoked emergency authorization of the last monoclonal antibody treatment because it wasn’t expected to have much of an effect against Omicron sub-variants.

    In contrast to monoclonal antibody therapies, Levine said, convalescent plasma donated by patients who have recovered from the virus is a treatment that evolves with the pandemic. Because it has antibodies that attach to multiple different parts of the virus, there are still opportunities to attach to a receptor even after the virus mutates and morphs some of its receptors. It’s also less expensive to produce than pharmaceutical antivirals.

    In the first year of the pandemic, Levine said, before the development of vaccines and effective treatments, researchers tried many treatment strategies in order to quickly find something that worked to save lives.

    “When the next big pandemic hits, we’re going to be in a very similar situation,” Levine said. “Yet at least next time, we’ll have research like this to inform our strategy.”

    Journal reference:

    Levine, A.C., et al. (2023) COVID-19 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-analysis of Individual Participant Data From Five Randomized Trials. Clinical Infectious Diseases. doi.org/10.1093/cid/ciad088.

    Canine distemper now threatens big cats in Nepal

    Researchers with the College of Veterinary Medicine have confirmed the first cases of canine distemper virus (CDV), which can cause fatal neurological disease, in tigers and leopards in Nepal.

    “Canine distemper virus has been repeatedly identified as a threat to wild carnivores and their conservation,” said Martin Gilbert, Cornell Wildlife Health Center wild carnivore health specialist and associate professor of practice in the Department of Population Medicine and Diagnostic Sciences. “This study is a first step to understanding the potential impact for Nepalese tiger and leopard populations.”

    Although researchers have suspected distemper was infecting these species, the study, published Jan. 28 in the journal Pathogens, is the first definitive proof of infection in Nepal’s big cats. The survey found 11% of tigers (three out of 28) and 30% of the leopards (six out of 20) had antibodies to CDV, indicating prior infection with the virus.

    Relatively little is known about the status of Nepal’s leopards, but scientists believe the population is in decline due to a combination of poaching, habitat loss and human-wildlife conflict. Leopards also face increasing competition for space due to the expansion of the country’s tiger population. Could CDV push them even further into decline?

    Unlike leopards, “tigers are enjoying a resurgence in Nepal,” Gilbert said. “Their national population has almost tripled in size over the past 12 years — however, globally the species remains endangered.” As the larger and stronger of the two species, tigers have been displacing leopards from national parks and forcing them into areas with more people, where they often prey on street dogs.

    Based on the findings of this paper, these dogs may be the source of infection. “We already know CDV is circulating in the Nepali dog population” said Dr. Jessica Bodgener, a veterinarian with Wildlife Vets International, who co-authored the paper, “and that leopards frequently eat dogs, while tigers do not. When we found a greater exposure in leopards it seemed like a good fit, but we need more evidence to be sure. And we can’t forget three tigers also tested positive. If tigers aren’t eating dogs, it raises the question, how did these animals get infected? The situation may not be straightforward.” Other species that could be acting as reservoirs include wild carnivores such as jackals and civets.

    The team examined blood samples collected from tigers and leopards between 2011 and 2021 by veterinarians working for Nepal’s Department of National Parks and Wildlife Conservation and the National Trust for Nature Conservation (NTNC). These were opportunistic samples, with most of the captures occurring as part of routine wildlife management. Routine collection and archiving of samples like these are important for investigating disease.

    In many places, CDV surveillance is hampered by a lack of local laboratories set up to run the appropriate tests. Access to specialist international labs can be blocked by export bans or slowed by permit application processes. To sidestep these issues, Gilbert’s team chose not to export the samples, but to partner with the Agricultural and Forestry University in Chitwan to establish testing in Nepal, something they hope to see replicated elsewhere.

    “Establishing national testing facilities that can support coordinated CDV research and surveillance efforts is both highly desirable and achievable, and should lead to increased sampling and collaboration,” Gilbert said.

    With the presence of the virus confirmed in these populations, the research team recommends several immediate actions:

    “Since 2014, we have seen 10 leopards showing neurological disease that could be consistent with CDV infection,” says Dr. Amir Sadaula, NTNC veterinarian, who led the Nepali research team. “With increased awareness, we plan to confirm future cases and obtain genetic sequences to help determine the source of infections.”

    Gilbert and his team plan to continue their work in Nepal, particularly on the under-studied leopard. Research is already underway to introduce more comprehensive big cat health assessments in a bid to understand the potential roles of injury and disease in increasing the likelihood of conflicts with people. Meanwhile, ongoing ecological fieldwork is investigating how the predation of domestic dogs may be influencing the behavior and distribution of leopards outside of national parks.

    The study was funded by the Cornell Feline Health Center, Cornell Wildlife Health Center, Wildlife Vets International and two anonymous donors.

  • Jessica Bodgener, Amir Sadaula, Parbat Jung Thapa, Bhijay Kumar Shrestha, Kamal Prasad Gairhe, Suraj Subedi, Kiran Raj Rijal, Purushotam Pandey, Janardan Dev Joshi, Prakriti Kandel, Babu Ram Lamichane, Chiranjibi Prasad Pokheral, Naresh Subedi, Ram Chandra Kandel, Himal Luitel, Navapon Techakriengkrai, Martin Gilbert. Canine Distemper Virus in Tigers (Panthera tigris) and Leopards (P. pardus) in Nepal. Pathogens, 2023; 12 (2): 203 DOI: 10.3390/pathogens12020203
  • Cornell University

    Loneliness is making us physically sick, but social prescribing can treat it – podcast

    Social isolation and loneliness are increasingly becoming societal problems, as they contribute to polarization and affect our physical health. Mental health professionals, community advocates and health-care providers have been raising the alarm about this impending crisis.

    The pandemic may have exacerbated social isolation and the subsequent feelings of loneliness, but it did not invent it. In 2018, two years before the pandemic, the United Kingdom created a ministerial portfolio for loneliness. Japan, where nearly 40 per cent of the population report experiencing loneliness, began a similar position in 2021.

    In this episode of The Conversation Weekly podcast, we speak to three researchers who invite us to more deeply consider loneliness and social isolation, and their impacts on our health and society.

    Ananya Chakravarti is an associate professor of history at Georgetown University in Washington in the U.S. As a historian of emotions, Chakravarti has studied expressions of loneliness in Indian devotional poetry.

    “If you read the poetry, it’s often expressing a deep and acute pain. Of course, it’s within that sense of being separated from the beloved that the world opens up spiritually for the devotee. So it’s an interesting kind of experience, in that sense of torment caused through separation.”

    In studying the history of loneliness, Chakravarti has found as opposed to the loneliness of choosing solitude for religious or creative purposes, today’s loneliness is a product of our modern lives.

    “We seem to live in this highly globalized world,” she points out, and “there’s so many more ways to be connected. Travel is so much easier. You have social media. And yet, actual experiences of loneliness are probably very much on the rise if you look at the cultural production around loneliness as a very modern phenomenon.”

    It’s this modern loneliness that is having a significant impact on our health.

    Julianne Holt-Lunstad, a professor of psychology and neuroscience at Brigham Young University in the U.S., has studied the impacts of loneliness on people’s health.

    “Being alone can activate these kinds of responses in our brain — and ultimately our bodies — that are associated with the threat response. And so we’re more hyper-vigilant to threats in our environment, as well as having to, in essence, handle every challenge in our life on our own. Our brains have to be more active, and this requires more metabolic resources.”

    This stress response triggers an inflammatory response which, over time, can contribute to conditions including cardiovascular disease and cognitive health.

    Read more:
    Social isolation linked to higher levels of inflammation – new study

    Social isolation is the absence of meaningful social connections, and so addressing its effects is not as simple as being around others. It requires building relationships of trust, belonging and support.

    The World Health Organization has identified social isolation as a social determinant of health, finding its impact to be “comparable to that of other well-established risk factors such as smoking, obesity, and physical inactivity,” especially for the elderly.

    Kate Mulligan, an assistant professor at the Dalla Lana School of Public Health in Canada, advocates for a health-care approach called social prescribing to address the health effects of loneliness.

    “Social prescribing is a way to use health care visits to reconnect people with nonclinical supports, community supports, that improve their health and well-being,” she explains.

    While it is a new approach, it’s firmly rooted in evidence that connecting people to others can help address some of their health-care needs.

    “Harm reduction communities have led by example and shown that peer workers create that welcoming environment in a way that is meaningful for people who use drugs.”

    But the impacts of loneliness are not just physical. Loneliness can create a feedback loop that increases polarization within society.

    Holt-Lunstad points out that “there’s vulnerability in terms of others that are not trusted. And so it may be considered very natural to want to have alliances and allegiances to your own group and to distrust other groups. And this unfortunately has led to a very common us-versus-them mentality, where people are isolating themselves within their groups of like-minded people.”

    And while loneliness is experienced on an individual level, it is caused by much larger structural problems. As Chakravarti points out, “if we don’t address it or think about this as a social problem, as a social challenge as opposed to an individual affliction, we’re going to not be able to address it.”

    Listen to the full episode of The Conversation Weekly to find out more.

    This episode of The Conversation Weekly was produced and written by Nehal El-Hadi and Mend Mariwany, who is also the show’s executive producer. Sound design is by Eloise Stevens, and our theme music is by Neeta Sarl. Music used in this episodes includes Duduk Music by Buddha’s Lounge.

    You can find us on Twitter @TC_Audio, on Instagram at @theconversationdotcom or via email. You can also sign up to The Conversation’s free emails here. A transcript of this episode will be available soon.

    Listen to The Conversation Weekly via any of the apps listed above, download it directly via our RSS feed, or find out how else to listen here.

    Nehal El-Hadi

    Daniel Merino

    Ananya Chakravarti

    Julianne Holt-Lunstad

    Kate Mulligan

    The Conversation