Rheumatoid arthritis (RA) is a chronic autoimmune disease that is associated with aberrant immune responses. In a recent analysis published in Arthritis & Rheumatology, people with RA and those at risk for the disease had higher blood levels of antibodies against a protein expressed by Prevotella copri, a common gut bacteria.
The study compared 98 participants with established RA who were compared with 98 controls without the condition, as well as 67 participants at high risk for RA who were compared with 67 controls. The researchers measured levels of antibodies against Pc-p27, a protein expressed by P. copri.
Participants with RA had significantly higher levels of IgA anti-Pc-p27 antibodies and trends towards higher levels of IgG anti-Pc-p27 antibodies when compared to their matched controls. When stratified by early versus established RA, early RA participants had median values of IgG anti-Pc-p27 antibodies that were overall higher, whereas median values of IgA anti-Pc-p27 were statistically significantly higher in participants with established RA, compared with their matched controls.
The authors noted that additional research into the roles of this and other microorganisms in rheumatoid arthritis is warranted.
“Our hope is that these findings can help to further elucidate the complex etiologic role of bacterial commensals in people who are at-risk of developing RA and in those with RA so that targeted therapies can be developed with the goals of providing better treatment and ultimately, prevention of the disease,” said corresponding author Jennifer A. Seifert, MPH, of the University of Colorado Denver.
A study published in PLOS ONE suggests that interacting with moderately active people is an important factor that could influence sedentary people into becoming more active. The researchers developed a mathematical model that takes into account the influence of social interactions on community exercise trends.
To help address shortfalls in people getting recommended levels of exercise, Ensela Mema of Kean University in Union, New Jersey, and colleagues drew on previous research showing that social interactions with peers can play a key role in boosting physical activity within a community. In line with that knowledge, they developed a mathematical model that simulates how social interactions can affect a population’s exercise trends over time. The model incorporates data from the US Military Academy.
The model simulations showed that, without social interactions, populations experienced a long-term decrease in physically active individuals, and sedentary behaviour began to dominate. However, when the simulations included social interactions between sedentary and moderately active people, sedentary populations became more physically active in the long term. Still, in simulations where moderately active people became more sedentary over time, overall physical activity trends plummeted.
While these simulations were not validated with real-world data, the researchers say they provide new insights that could inform public health efforts to boost community physical activity levels. The researchers outline a number of recommendations for such efforts, such as social activities designed to boost interactions between sedentary and moderately active people.
The researchers said that more research will be needed to better understand the balance between encouraging exercise among sedentary people while retaining activity levels in moderately active people.
The authors added: “We have traditionally directed physical activity interventions by engaging sedentary individuals to become more active. Our model suggests that focusing on the moderately active population to sustain their activity and increasing their interactions with sedentary people could stimulate higher levels of overall physical activity in the population.”
Using brain ‘organoids’, researchers at Karolinska Institutet have found that COVID infection results in damage from immune cells and gene expressions similar to those found in neurodegenerative disorders. Their findings were published in Molecular Psychiatry.
The findings could help to identify new treatments against persistent cognitive symptoms after a COVID infection.
Neurological symptoms in ‘long COVID’ have been widely reported but the underlying mechanisms for this remains unknown. To find out, the study’s researchers created brain organoids from human induced pluripotent stem (iPS) cells. The model differs from previous organoid models as the researchers also included the brain immune cells – microglia – in the model. In the infected models, microglia excessively engulfed synaptic structures and displayed upregulation of factors involved in phagocytosis. The developed model and the findings in the study could help to guide future efforts to target cognitive symptoms in the aftermath of COVID and other neuroinvasive viral infections.
Post-infection cognitive deficits
“Interestingly, our results to a large extent mimic what has recently been observed in mouse models infected with other neuroinvasive RNA viruses such as the West Nile virus. These viruses are also linked to residual cognitive deficits after the infection, and a persisting activation of microglia leading to an excessive engulfment of synapses, which has been suggested to drive these symptoms. Multiple studies have now also reported remaining cognitive symptoms after a COVID infection, as well as an increased risk of receiving a diagnosis of a disorder characterised by cognitive symptoms,” says co-first author of the study Samudyata, a postdoctoral fellow at Karolinska Institutet.
Connections to Parkinson’s and Alzheimer’s disease
Microglia also carry out important regulatory functions of the neuronal circuitries in the brain, one of which is engulfing unwanted synapses, a process that is believed to improve and maintain cognitive functions. However, excessive engulfment of synapses has been linked to both neurodevelopmental disorders, such as schizophrenia, as well as to neurodegenerative disorders including Alzheimer’s disease.
By sequencing genes in single cells, the authors could also study how different cell types in the model responded to the virus.
“Microglia displayed a distinct gene signature largely characterized by an upregulation of interferon-responsive genes, and included pathways previously linked to neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease. This signature was also observed at a later time-point when the virus load was minimal,” says co-author of the study Susmita Malwade, a doctoral student at Karolinska Institutet.
The researchers will now study how different pharmacological approaches can reverse the observed changes in the infected models.
A team of researchers analysed centuries-old DNA samples from plague burial pits in London identified genes that protected some against the Black Death that swept through Europe, Asia and Africa nearly 700 years ago. Their study, which showed how those aspects of our immune systems have continued to evolve since that time, is published in the journal Nature.
According to the researchers’ findings, the same genes that once conferred protection against the Black Death are today linked to an increased susceptibility to autoimmune diseases such as Crohn’s and rheumatoid arthritis.
The team focused on a 100-year window before, during and after the Black Death, which reached London in the mid-1300s. It remains the single greatest human mortality event in recorded history, killing upwards of 50% of the people in what were then some of the most densely populated parts of the world.
More than 500 ancient DNA samples were extracted and screened from the remains of individuals who had died before the plague, died from it or survived the Black Death in London, including individuals buried in the East Smithfield plague pits used for mass burials in 1348–9. Additional samples were taken from remains in Denmark.
Scientists searched for signs of genetic adaptation related to the plague, which is caused by the bacterium Yersinia pestis.
They identified four genes that were under selection, all of which are involved in the production of proteins that defend our systems from invading pathogens and found that alleles of the genes either protected or rendered one susceptible to plague.
Individuals with two identical copies of a particular gene, known as ERAP2, survived the pandemic at a much higher rates than those with the opposing set of copies, because the ‘good’ copies allowed for more efficient neutralisation of Y. pestis by immune cells.
“When a pandemic of this nature – killing 30 to 50 per cent of the population – occurs, there is bound to be selection for protective alleles in humans, which is to say people susceptible to the circulating pathogen will succumb. Even a slight advantage means the difference between surviving or passing. Of course, those survivors who are of breeding age will pass on their genes,” explained evolutionary geneticist Hendrik Poinar, an author of the Nature paper.
Europeans living at the time of the Black Death had were extremely vulnerable at first as they had no recent exposure to Yersinia pestis. Mortality rates fell in subsequent waves of the pandemic over the following centuries.
Researchers estimate that people with the ERAP2 protective allele (the good copy of the gene, or trait), were 40 to 50 per cent more likely to survive than those who did not.
“The selective advantage associated with the selected loci are among the strongest ever reported in humans showing how a single pathogen can have such a strong impact to the evolution of the immune system,” says human geneticist Luis Barreiro, an author on the paper, and professor in Genetic Medicine at the University of Chicago.
The resignation of renowned breast cancer specialist surgeon Professor Carol-Ann Benn from the Helen Joseph Hospital has fuelled concerns about the loss of expertise for the public health sector amid existing pressures on cancer services in Gauteng. Concerns have also been raised about what some labelled an unconducive workplace culture and worsening working conditions at the hospital.
Some hospital insiders called the environment toxic with patriarchy and petty hierarchies. This, compounded with ongoing operational challenges, is having a dire impact on staff retention and the quality of patient care.
Benn’s last day at the clinic at the end of September brought to a close a 17-year-long relationship with the public health facility. Volunteers from the not-for-profit Breast Health Foundation which Benn is a founding director of, have backed her decision and have also ended their services at the hospital.
“The Breast Health Foundation’s decision to withdraw services in solidarity with Professor Benn comes after months of trying to address barriers to the provision of quality patient care and a lack of support from senior management,” its statement read.
Louise Turner, chief operations officer at the Foundation, says after an initial phone conversation there have been no further discussions on a way forward to restart their services there. The Foundation had five patient navigators and three volunteers based at Helen Joseph Hospital (HJH). Navigators guide patients through their journey from diagnosis to treatment, help to link them to services, and to advance them along long cancer treatment waiting lists. They also offer psycho-social counselling and become a practical support net. Spotlight previously reported on their work here.
Responding to the concerns raised, the Gauteng Department of Health, however, says no patients will be affected negatively by the exodus of Benn and the Foundation and that the clinic remains fully operational.
Spokesperson for the department, Kgomotso Mophulane, says, “The Breast Clinic is not closed at Helen Joseph Hospital. It is only one employee who has resigned but the clinic continues to have other specialists who run the clinic.”
Mophulane says that the Breast Health Foundation does not have a formal agreement with the department of health and that “existing agreements with other facilities such as Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) continue”.
If the shoe doesn’t fit
Benn has straddled public and private healthcare throughout her 30-year career and she remains head of the Netcare Breast Care Centre and continues to lecture at Wits University’s department of surgery.
“My patients have taught me so much over the years,” says Benn. “Leaving Helen Joseph after 17 years has been a struggle. There was harassment and an obstructive workplace culture that made our daily working lives impossible, but I can’t spend my time getting into trouble for trying to find solutions. And if my patients have to face so much to survive, then I can survive this too.”
Benn says she’s “stepping outside to find solutions”. She says her next focus is to find ways to reform access for cancer treatment on lower-level medical aid schemes without massive co-payments and her work in the public sector continues. Benn says she is managing her existing Helen Joseph patients at her practice at Milpark Hospital and says she’s already had positive advances to set up a “patient-centered unit for equitable care for public patients within the private sector” that will be ready to launch within the next few weeks.
“I don’t fit the shoe of government but I’m leaving to innovate in other ways because no one should be turned away from a specialist unit because they don’t have the money or because they don’t live in a catchment area.”
According to Helen Joseph Hospital CEO Dr Relebohile Ncha, Benn had raised issues of “challenges she had with her supervisor, which is one of the clinical managers. Unfortunately, these issues were brought forward at the time of her resignation and therefore there was no time to redress [sic] the issues raised directly with her.”
Ncha adds that the labour relations department would have dealt with the “workplace relationship challenges”. She also says the psychology department will provide counselling for cancer patients in the absence of the Foundation.
According to Ncha, the system in place remains that new patients are seen on a Tuesday for diagnosis and are “booked within a week” for further treatment. Ncha says there are currently between 400 and 550 outpatients and between 20 and 30 patients booked for surgery per month. She also says there are no oncology specialists at Helen Joseph Hospital, as this care is referred to CMJAH.
A long history
According to Turner, the Breast Health Foundation over the years has helped turn the clinic into a hub of excellence. “So much of what is in the clinic we raised money for – from painting the walls, décor, to the chairs and furniture in the counselling rooms.”
Turner says they’ve helped around 200 000 patients to be “navigated” through the maze of cancer diagnosis and treatment at the facility and around 10 000 people who were diagnosed with cancers were supported through their journey of ups and downs of cancer treatment.
But she says it was clear the workplace environment had become increasingly untenable for Benn and also the Foundation’s team. According to Turner, Benn was being summoned to meetings constantly from the hospital floor to answer for her decisions and was criticised and undermined for veering off administrative procedures.
“Professor Benn’s approach has always been about putting the patient first. She has used her own money to buy things like surgical drains or surgical gloves so that she could do her work. She always made a plan, including squeezing in surgeries and she did accept patients who do not fall into the Helen Joseph catchment area because of their need to access services. But senior management would make her life hell unnecessarily over this,” she says.
‘a family of survivors’
Patient navigator for the Breast Health Foundation Ouma Mamatela was a patient of Benn in 2016 before she joined the Foundation. She says patients at HJH are now paying the price for “egos and mismanagement”.
“It’s going to be very, very hard for patients who expect to find the navigators there to hold their hand through everything. We built up a family of survivors. I am still waking up very early on Tuesdays and Thursdays because those were the days I knew I was getting up to serve our patients at Helen Joseph,” says Mamatela.
Ouma Mamatela, cancer survivor and cancer patient navigator. PHOTO: Rosetta Msimanga/Spotlight
She adds that Benn’s out-of-the-box thinking, accessibility to patients, and transparency in the way she worked irked senior male managers and doctors.
“Professor Benn is one person who speaks to everyone. She doesn’t make herself untouchable. I want to say to those managers that they need to put their egos aside because it is the patients that need quality care the most who are suffering,” she says.
‘you can feel that it’s different now’
Twenty-six-year-old *Thandiwe was one of Benn’s last patients at Helen Joseph. Her mother *Thawe says that she and her daughter have experienced both kindness and professional care from Benn and the Foundation and have also borne the brunt of bureaucratic pettiness and outright bullying from senior clinical management at the hospital.
Thawe asked for their identities to be protected, fearful of being victimised at the hospital.
Thawe tells first how her family’s world came to a crashing halt when Thandiwe found a lump in her breast in July this year. Thandiwe, who was living in the North West province at the time, had a biopsy done at the Moses Kotane District Hospital but says she never received her results.
Being unwell she couldn’t keep her job and eventually came to Johannesburg to be with her mom. Thawe’s employer donated R10 000 towards her daughter’s treatment.
“When I asked in the office and googled about where I could get help, the name that kept coming up was Professor Benn’s so we decided to use the money to do another biopsy and to see Professor Benn at her private practice in Milpark.
“When we saw the Prof she was so kind and informative. She explained everything and gave us some peace even when she confirmed that Thandiwe was cancer-positive. When it came time to pay, she realised that we didn’t have medical aid so she told the receptionist not to charge us anything,” says Thawe.
Benn told them to come to her clinic day at Helen Joseph so the next steps of surgery could begin. Benn also advised plastic surgery at the same time as the removal of the cancerous lump would significantly reduce the size of Thandiwe’s left breast.
On the clinic day, Thawe says they waited for hours but she adds, “Everyone from the Foundation was friendly and explained what was happening. When it’s like that you accept that you have to wait.”
But then Thawe was told her daughter would not be admitted for surgery and that her case was being referred to Charlotte Maxeke Johannesburg Academic Hospital instead.
“Another doctor took Thandiwe off the surgery list and sent a junior doctor to us with the referral letter without any explanation,” she says.
At Charlotte Maxeke, she says Thandiwe was sent from department to department and could not get admitted there either. Eventually, a desperate Thawe returned to Helen Joseph to demand an explanation.
“I was taken to see these three men in the clinical manager’s office. They showed no empathy – they just didn’t care. They just kept saying ‘wrong catchment area’, that they could not do the plastic surgery at Helen Joseph, and that Benn should never have told us to come to Helen Joseph,” she says.
Thawe and Thandiwe stayed in contact with Benn. Mother and daughter kept fighting and eventually took their complaint to hospital CEO Ncha. Only then was Thandiwe’s surgery approved.
She says Benn kept her promise to operate on Thandiwe and also made arrangements with a plastic surgeon from Charlotte Maxeke to help with the reconstructive surgery for Thandiwe.
“I cannot find the words to thank Professor Benn for all she did to save my daughter’s life,” Thawe says.
But she says since Benn and the Foundation’s exodus at the end of September, “it’s been a mess at Helen Joseph”. She accompanied Thandiwe to have a drain removed and her bandages and dressings changed at the beginning of October. “All those ladies in pink that used to help us were gone. All the patients were just sitting without knowing what was happening and no one telling us anything. When we eventually saw a doctor she said she didn’t know how to remove the drains. She took some photos of Thandiwe and told us to come back the next day.
“I had to change Thandiwe’s bandages myself and tell the nurses how to tape the drain. You can feel that it’s different now without Benn and the navigators,” she says. Eventually, they were forced to go to Charlotte Maxeke where the plastic surgeon that operated on Thandiwe helped to remove the drain properly. “It’s been hell at HJH – I worry for what will happen to other women who cannot fight like we did,” she says.
Dozens of Helen Joseph patients have also since weighed in via social media in support of Benn and the Foundation, sharing their stories and also their deepening worries about what comes next for their treatment.
**Patients needing to get in touch with the Breast Health Foundation can continue to do so via their support line on 0860 283 343.
Chronic back pain, a pervasive complaint in modern society, has many treatments including physiotherapy. A meta-analysis published in theJournal of Pain, has delivered new insights into the most effective therapies for back pain and revealed that individualised exercise treatments were quite effective, especially when combined with cognitive behavioural therapy.
The researchers analysed 58 randomised controlled trials (RCTs) of over 10 000 patients worldwide with chronic low back pain. First, the data relevant to the topic were filtered out of the original manuscripts and then evaluated in groups. When evaluating these data, the researchers examined on the one hand whether and to what extent standard forms of treatment and individualised treatment differ in terms of the result. “Individualised” means that there is some type of personal coaching, where therapists specifically target the potentials and requirements of each patient and decide together with them how their therapy should look.
The study concluded that individualised treatment for chronic back pain led to a significantly increased effect in comparison to standard exercise therapies. The success rate in pain relief was 38% higher than with standard treatment. “The higher effort required for individual treatment is worthwhile because patients benefit to an extent that is clinically important,” says lead author Dr Johannes Fleckenstein from the Institute of Sport Sciences at Goethe University Frankfurt.
The research team then compared a third group of treatment methods alongside the standard and individualised ones. In this group, individualised training sessions were combined with cognitive behavioural therapy (CBT). This procedure is based on the assumption that negative thoughts and behaviours surrounding pain tend to exacerbate it. Through CBT, pain patients learn to change the way they handle it. They stop being afraid to move or are taught tactics for coping with pain. This makes them realise that they are by no means helpless. But what does the psychotherapeutic support through CBT actually contribute to the success of the treatment? Analysis of the data revealed the following: when an individualised approach and CBT were combined, the success rate in terms of pain relief was an impressive 84% higher than with standard treatment. The combined therapy, also called multimodal therapy, thus led to the best result by far.
Dr Fleckenstein sees in the study “an urgent appeal to public health policy” to promote combined therapies both in terms of patient care and remuneration. “Compared to other countries, such as the USA, we are in a relatively good position in Germany. For example, we issue less prescriptions for strong narcotic drugs such as opiates. But the number of unnecessary X-rays, which, by the way, can also contribute to pain chronicity, and inaccurate surgical indications is still very high.” This is also due, Dr Fleckenstein said, to economic incentives for such interventions. The situation is different for organisations working in the area of pain therapy, he said. Although these are not unprofitable, they are not a cash cow for investors either. In his view, it is important here to improve the economic conditions. After all, pain therapy saves a lot of money in the long run as far as health economics are concerned, whereas tablets and operations rarely lead to medium and long-term pain relief.
Psychostimulants are commonly used as treatments of psychiatric disorders or to improve cognition, but the benefits of these drugs are not the same for everyone, as their effects vary greatly both across individuals and within the same patient. This variability hinders treatment strategies in psychiatry, and the reasons behind it are still not clear. Now, a study published in PNAS, researchers reported advances in understanding why this is.
One such psychostimulant is methylphenidate (Ritalin), which is used to treat attention deficit hyperactivity disorder (ADHD), and has significant variability in efficacy. In addition to treating ADHD, methylphenidate is widely used by healthy people for its cognition-improving effects. Methylphenidate acts in part by increasing levels of dopamine, a neurotransmitter involved in the brain’s reward system.
The researchers tested the hypothesis that the effects of methylphenidate on learning based on reward or punishment depend on the baseline levels of dopamine in a person’s brain. To test this, one hundred young healthy adults received (in different sessions) methylphenidate, sulpiride (a medication used to treat symptoms of schizophrenia that acts more selectively on dopamine receptors), or a placebo, and were later scanned with functional magnetic resonance imaging (fMRI) during a reward/punishment reversal learning task. In this task, participants learned to predict whether a picture (of a face or a landscape) that is selected by the computer is followed by reward or punishment. A reward outcome consisted of a green smiley and a + €100 sign. A punishment consisted of a red sad smiley and a – €100 sign. Whether the face or the landscape was associated with reward or punishment changed frequently in the task, so to perform well people had to continue to pay attention and flexibly update their behaviour based on prediction errors.
The researchers observed that the degree to which both methylphenidate and sulpiride improved reward compared with punishment learning depends on baseline dopamine synthesis capacity. These learning effects were also were accompanied by increased activity in the striatum, a dopamine-rich region deep inside the brain, and also by increased specificity of the activity in regions of the cortex near the back of the brain that are specialised for processing faces and landscapes.
Their findings provide strong support for two hypotheses related to methylphenidate: First, that dopamine enhances task-relevant cortical signals by acting on the striatum. Second, that differences between individuals in dopamine synthesis capacity in the striatum explain the variability in the drug’s cognitive effects.
In a clinical trial, researchers found that, after a course of vancomycin, faecal microbiota transplantation (FMT) resolved Clostridioides difficile infections significantly more effectively than standard care alone. The treatment was so effective that further participant recruitment was halted. The findings were published in The Lancet Gastroenterology and Hepatology.
The results of the randomised, double-blind, placebo-controlled trial are extremely encouraging, said Simon Mark Dahl Baunwall, a PhD student at the Department of Clinical Medicine and a doctor at Aarhus University Hospital.
“Our new study shows that we can effectively cure the infection through the early use of faecal microbiota transplantation (FMT) after completing the standard treatment, to prevent relapses,” he said.
Few treatment options are available for the urgent threat of C. diff infections. Microbiota restoration with faecal microbiota transplantation is an effective treatment option for patients with multiple recurring episodes of C. diff. The researchers compared the efficacy and safety of faecal microbiota transplantation compared with placebo after vancomycin for first or second C. diff infection.
At a Danish hospital, 42 eligible patients with first or second C. difficile infection were randomly assigned to either faecal microbiota transplantation or placebo administered on day 1 and between day 3 and 7, after they had received 125mg oral vancomycin four times daily for 10 days. The primary endpoint was resolution of C difficile-associated diarrhoea (CDAD) eight weeks after treatment, with patients followed for eight weeks or until recurrence.
Due to the efficacy The primary outcome and safety outcomes were analysed in the intention-to-treat population, which included all randomly assigned patients.
Findings
The trial was stopped after the interim analysis done on April 7, 2022 for ethical reasons because the placebo group had a much lower rate of resolution at week 8 (33%) than the treatment group (90%). The absolute risk reduction was 57%.
“In rare cases, it can happen that you discover that the treatment you are investigating is so effective that it is ethically indefensible to continue,” said Baunwall.
“Our study is one example, in that the new FMT treatment is so much better than the standard treatment with antibiotics that it would be unethical to continue, because the patients in the control group would risk not receiving the FMT treatment.”
Overall, 204 adverse events occurred, with one or more adverse events being reported in 20 of 21 patients in the FMT group and all 21 patients in the placebo group, with the most common being diarrhoea and abdominal pain.
Interpretation
The study authors concluded that FMT in patients with first or second C. diff infection, is highly effective and superior to the standard of care vancomycin alone in achieving sustained resolution from C. diff.
Neutrophils are the body’s first line of defence against infection, which can be activated when foreign pathogens stress the body. When overactivated, neutrophils can damage the body’s own tissues. Lung tissue is saturated with blood vessels, making them very susceptible to neutrophil attacks. If severe enough, acute lung injuries can lead to acute respiratory distress syndrome (ARDS), the leading cause of death due to COVID.
Reporting in JCI Insight, Cold Spring Harbor Laboratory (CSHL) researchers have found a drug candidate that can prevent lethal lung inflammation in mice by inhibiting a protein called PTP1B. Their discovery may help develop better treatments for severe inflammatory conditions like sepsis and COVID.
“When you think about COVID, acute lung injury and ARDS underlie the fatal aspects of the disease,” leader researcher Nicholas Tonks, professor of cancer research says. “And so, when the pandemic took hold, we were wondering whether there was anything we could do to help, to provide an understanding of this aspect of the disease and suggest ways it could be treated.”
Tonks’ graduate student Dongyan Song investigated whether using a PTP1B inhibitor drug candidate could dampen the lethal consequences of overactive neutrophils in mice. She found that pretreating mice with the PTP1B inhibitor reduced lung tissue damage. When untreated, less than half of the mice survived acute lung injuries and ARDS. But when pretreated, they all survived.
The researchers exploited a natural process, called neutrophil aging, that the body uses to control the immune cell’s lifespan. As they age, neutrophils become less dangerous. Tonks’ team discovered PTP1B inhibition speeds up neutrophil aging. “An aged neutrophil is like a soldier without a weapon,” Song explains. “So regardless of how many neutrophils flood an area, they won’t be able to do serious damage.”
Going forward, he and Song are working to increase the understanding of how PTP1B inhibitors affect the immune system. Tonks hopes his lab’s continued research leads to new treatments and preventative measures for various inflammatory diseases.
Tonks’ lab studies signal transduction, the process that controls how cells respond to signals from their environment. In particular, they focus on the PTP protein family, which Tonks discovered over 30 years ago. Since then, he’s sought to develop small molecule drug candidates that target these proteins, which can provide new approaches for treating major human diseases including cancer and metabolic and neurodegenerative diseases.
Researchers have found that a recently discovered virus in a Russian bat that is similar to SARS-CoV-2 may be able to infect humans and, if it were to spillover, is resistant to current vaccines.
Reporting in PLOS Pathogens, researchers discovered that spike proteins from the bat virus, named Khosta-2, can infect human cells and is resistant to both the monoclonal antibodies and serum from individuals vaccinated for SARS-CoV-2. Both Khosta-2 and SARS- CoV-2 belong to the same sub-category of coronaviruses known as sarbecoviruses.
“Our research further demonstrates that sarbecoviruses circulating in wildlife outside of Asia – even in places like western Russia where the Khosta-2 virus was found – also pose a threat to global health and ongoing vaccine campaigns against SARS-CoV-2,” said Michael Letko, WSU virologist and corresponding author of the study.
Letko said the discovery of Khosta-2 highlights the need to develop universal vaccines to protect against sarbecoviruses in general, rather than just against known variants of SARS-CoV-2.
“Right now, there are groups trying to come up with a vaccine that doesn’t just protect against the next variant of SARS-2 but actually protects us against the sarbecoviruses in general,” Letko said. “Unfortunately, many of our current vaccines are designed to specific viruses we know infect human cells or those that seem to pose the biggest risk to infect us. But that is a list that’s everchanging. We need to broaden the design of these vaccines to protect against all sarbecoviruses.”
While hundreds of sarbecoviruses have been discovered in recent years, predominantly in bats in Asia, the majority are not capable of infecting human cells. The Khosta-1 and Khosta-2 viruses were discovered in Russian bats in late 2020, and it initially appeared they were not a threat to humans.
“Genetically, these weird Russian viruses looked like some of the others that had been discovered elsewhere around the world, but because they did not look like SARS-CoV-2, no one thought they were really anything to get too excited about,” Letko said. “But when we looked at them more, we were really surprised to find they could infect human cells. That changes a little bit of our understanding of these viruses, where they come from and what regions are concerning.”
Letko teamed with a pair of researchers in Washington State University’s to study the two newly discovered viruses. They determined Khosta-1 posed low risk to humans, but Khosta-2 demonstrated some troubling traits.
The team found that like SARS-CoV-2, Khosta-2 can use its spike protein to infect cells by attaching to a receptor protein, called angiotensin converting enzyme 2 (ACE2), found throughout human cells. They next set out to determine if current vaccines protect against the new virus.
Using serum derived from COVID-vaccinated human populations, the team saw that Khosta-2 was not neutralised by current vaccines. They also tested serum from people who were infected with the omicron variant, but the antibodies, too, were ineffective.
Fortunately, Letko said the new virus is lacking some of the genes believed to be involved in pathogenesis in humans. There is a risk, however, of Khosta-2 recombining with a second virus like SARS-CoV-2.
“When you see SARS-2 has this ability to spill back from humans and into wildlife, and then there are other viruses like Khosta-2 waiting in those animals with these properties we really don’t want them to have, it sets up this scenario where you keep rolling the dice until they combine to make a potentially riskier virus,” Letko said.
