Publisher Health

For a year we have all lived under Covid-19 restrictions. But how have hospital staff dealt with fighting the pandemic at work and living under lockdown at home?Four staff from University Hospital Southampton tell the BBC about the impact of the last year on their home and work lives. Filmed/edited by Rachel PriceProduced by Alexander Littlewood

A University of Birmingham-led study of top-flight UK rugby players — carried out in collaboration with the Rugby Football Union (RFU), Premiership Rugby, and Marker Diagnostics — has identified a method of accurately diagnosing concussion using saliva, paving the way for the first non-invasive clinical test for concussion for use in sport and other settings.
Following the team’s previous research, which identified that the concentration of specific molecules in saliva changes rapidly after a traumatic brain injury, the researchers embarked on a three-year study in elite rugby to establish if these ‘biomarkers’ could be used as a diagnostic test for sport-related concussion.
Using DNA sequencing technology in the laboratory at the University of Birmingham, the research team tested these biomarkers in saliva samples from 1,028 professional men’s rugby players competing in English rugby’s top two leagues — the Premiership and Championship.
The results of SCRUM (Study of Concussion in Rugby Union through MicroRNAs), published today (March 23) in the British Journal of Sports Medicine, has for the first time shown that specific salivary biomarkers can be used to indicate if a player has been concussed. Additionally, the research has found these biomarkers provide further insights into the body’s response to injury as it evolves from immediately after trauma, to several hours and even days later.
The scientific breakthrough provides a new laboratory-based non-invasive salivary biological concussion test, which could have wide-reaching use and potential to reduce the risk of missing concussions not only in sport — from grassroots to professional levels — but also in wider settings such as military and healthcare.
In community sport, these biomarkers may provide a diagnostic test that is comparable in accuracy to the level of assessment available in a professional sport setting. While, at an elite level of rugby, the concussion test may be used in addition to the existing World Rugby Head Injury Assessment (HIA) protocol.

Scientists have found new, unexpected behaviors when SARS-CoV-2 — the virus that causes COVID-19 — encounters drugs known as inhibitors, which bind to certain components of the virus and block its ability to reproduce.
Published in the Journal of Medicinal Chemistry, the research provides key insights for advancing drug design and drug repurposing efforts to treat COVID-19.
Researchers at the Department of Energy’s Oak Ridge National Laboratory used neutron scattering to investigate interactions between telaprevir, a drug used to treat hepatitis C viral infection, and the SARS-CoV-2 main protease, the enzyme responsible for enabling the virus to reproduce.
They discovered unforeseen changes in the electric charges in the drug binding site of the protease enzyme that were not predicted by prevailing computer simulations.
“We found this particular protein — the SARS-CoV-2 main protease — which a lot of researchers are studying by computational methods, is behaving in a surprising way,” said lead author Daniel Kneller. “Our findings provide critical experimental data needed to improve computer modeling so that simulations more closely match reality.”
The virus reproduces by assembling long chains of proteins, or polyproteins, made from almost 2,000 amino acids that must be cut into smaller chains by the main protease. Finding a drug that effectively blocks or inhibits the protease function is paramount to preventing the virus from replicating and spreading to other healthy cells in the body.

When the human immunodeficiency virus infects cells, it can either exploit the cells to start making more copies of itself or remain dormant — a phenomenon called latency. Keeping these reservoirs latent is a challenge. A new paper, published in the Proceedings of the National Academy of Sciences, has found a way to look for chemicals that can keep the virus suppressed into its dormant state.
“The current drug treatments block healthy cells from becoming infected by the virus,” said Yiyang Lu, a PhD student in the Dar lab at the University of Illinois Urbana-Champaign. “The latent reservoir poses a bigger problem because it can start producing the virus at any time. Consequently, patients have to remain on antiretroviral therapy all their lives to prevent a viral rebound.”
So far, there are two types of drug treatment strategies: shock-and-kill, where reactivated cells are killed due to HIV, and a second drug cocktail prevents other cells from being infected, or block-and-lock, which forces the virus into a deep latent state so that it does not reactivate again. The problem with the first approach is that there are always some leftover reservoirs that do not get activated. The problem with the second approach, which the researchers are trying to solve, is that there aren’t many drugs that have been discovered.
Since the transition from latency occurs randomly, measuring the fluctuations in gene expression can provide more coverage than the average gene expression. “Commercial drug screens usually look at mean gene expression. Instead, we used a drug screen that looks at fluctuations in gene expression. Our screen allowed us to therefore find more compounds that could have been overlooked,” Lu said.
“We implemented a time-series drug screening approach that are less commonly used in other labs,” said Roy Dar, an assistant professor of bioengineering at Illinois and faculty member of the Carl R. Woese Institute for Genomic Biology. The researchers used a T- cell population, which is a reservoir for HIV, that had been infected by the virus. They imaged the cells in 15-minute intervals for 48 hours and tested over 1800 compounds. They looked at noise maps to identify which drugs can modulate the gene expression.
Using the screen, they were able to find five new latency-promoting chemicals, raising the possibility that similar screens can be successfully adapted to study other systems that exhibit variability in gene expression, such as cancer. They are currently working on understanding how the five novel drugs suppress viral reactivation. “We want to test if these drugs have off-target effects in terms of how many other genes they affect in the host cells,” Dar said. “We also want to test these drugs in patient samples to see whether these drugs suppress HIV in them.”
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Materials provided by Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign. Original written by Ananya Sen. Note: Content may be edited for style and length.

People who received a flu shot last flu season were significantly less likely to test positive for a COVID-19 infection when the pandemic hit, according to a new study. And those who did test positive for COVID-19 had fewer complications if they received their flu shot.
These new findings mean senior author Marion Hofmann Bowman, M.D., is continuing to recommend the flu shot to her patients even as the flu season may be winding down.
“It’s particularly relevant for vaccine hesitance, and maybe taking the flu shot this year can ease some angst about the new COVID-19 vaccine,” says Hofmann, an associate professor of internal medicine and a cardiologist at the Michigan Medicine Frankel Cardiovascular Center. Michigan Medicine is the academic medical center of the University of Michigan.
Researchers reviewed medical charts for more than 27,000 patients who were tested for a COVID-19 infection at Michigan Medicine between March and mid-July of 2020. Of the nearly 13,000 who got a flu shot in the previous year, 4% tested positive for COVID-19. Of the 14,000 who hadn’t gotten a flu shot, nearly 5% tested positive for COVID-19. The association remained significant after controlling for other variables including ethnicity, race, gender, age, BMI, smoking status and many comorbid conditions, Hofmann says.
People who received their flu shot were also significantly less likely to require hospitalization, although the researchers didn’t find a significant difference in mortality between the two groups. No one in the study tested positive for both infections at the same time.
The underlying mechanism behind the association isn’t yet clear, Hofmann says.

Scientists are examining a possible link to tinnitus. A businessman’s suicide has lent urgency to the research.The suicide of Kent Taylor, the founder and chief executive of the Texas Roadhouse restaurant chain, has drawn attention to a possible link between Covid-19 and tinnitus, the medical term for a constant ringing in the ears.Mr. Taylor suffered from a variety of symptoms following his illness, including severe tinnitus, his family said in a statement, adding that his suffering had become “unbearable.”Whether tinnitus is linked to Covid-19 — and if so, how often it occurs — is an unanswered question. Neither the World Health Organization nor the Centers for Disease Control and Prevention describes tinnitus as a symptom, although auditory problems are common in other viral infections.But tinnitus is on the list of symptoms of long Covid published by the United Kingdom’s National Health Service, along with fatigue, shortness of breath, dizziness and more. And a few recent case reports and studies have hinted at a potential link.A study published on Monday in the Journal of International Audiology that looked at nearly 60 case reports and studies found that 15 percent of adults with Covid-19 reported symptoms of tinnitus. The authors believe that the respondents were describing either a new condition or a worsening one, though they are following up with the 60 or so researchers to be certain about how the surveys were worded.“In the 24 hours since we published, I’ve received about 100 emails,” said Kevin Munro, a professor of audiology at the University of Manchester and a co-author of the study. “Almost of all of them were people saying, ‘I was so happy to read about this, because my doctor thought I was crazy when I mentioned tinnitus and now I know I’m not the only one.’”There is also some evidence that Covid-19 can aggravate symptoms among people who had tinnitus before they contracted the disease. A study published late last year in the journal Frontiers in Public Health surveyed 3,100 people with tinnitus and found that 40 percent of the 237 respondents who had contracted Covid-19 reported that their symptoms were “significantly exacerbated” following the infection.“There are a lot of viruses that have an impact on the ears, including measles, mumps and rubella,” said Dr. Eldre Beukes, the audiologist at Anglia Ruskin University in England who led the study. “It could also be the case that medication taken to combat Covid is making tinnitus worse. And there is a well-known link between tinnitus and stress.”Kent Taylor, founder and chief executive of the Texas Roadhouse restaurant chain.Ron Bath/Texas Roadhouse, via Associated PressThe study cited a variety of factors that have increased stress for nearly everyone in the pandemic, including fear of catching the coronavirus, and social distancing rules that have increased isolation and loneliness.Home-schooling has also raised stress levels, as has greater consumption of coffee and alcohol, Dr. Beukes added.Covid-19 has complicated life for tinnitus sufferers even if they have not contracted the virus, said Kim Weller, an I.T. specialist who lives in Houston and is part of a tinnitus support group based there.“There’s a gentleman in Ohio who I text and talk on the phone with and I’d describe him as being at the end of his rope,” she said. “He’s not working, trouble sleeping, living alone. His situation is definitely worse because of Covid, because he’s just so isolated.”Exactly why tinnitus affects certain people is a bit of a mystery. There are roughly 200 causes of the condition, including exposure to loud noises, stress, hearing loss and perforated eardrums. There is currently no cure. Patients are often treated with cognitive behavioral therapy — essentially, talk therapy designed to rewire thoughts and behaviors — or coached on how to habituate themselves to the condition.The C.D.C. found in a 2011-2012 survey — the most recent data available — that 15 percent of respondents said they had suffered some kind of tinnitus. Of them, 26 percent said it was constant or near constant ringing, and 30 percent described the condition as a “moderate” or “very big” problem in their lives.A very small group of people in Dr. Beukes’s study — seven — reported that Covid-19 brought on tinnitus for the first time. Just over half of people with tinnitus said the illness had left their symptoms unchanged.Curiously, 6 percent said they were less bothered by tinnitus after contracting the disease. Dr. Beukes speculates that for these people, a life-threatening condition had the effect of reframing the noise in their head.“Contracting Covid meant that in some cases they were struggling to survive, and that left them with a very different perspective,” she said.The roughly 40 percent of respondents who said that Covid-19 made their tinnitus worse includes people like Aisling Starrs of Derry, in Northern Ireland. She’d coped with hearing loss in her right ear her entire life. Two years ago, she gave birth to a daughter and within minutes noticed a buzzing in both ears that did not abate.“Then in September I got Covid, and it went straight for my ears,” said Ms. Starrs, who is an occupational therapist. “On a scale of one to 10, it was a three before Covid. Since then, it’s been a seven.”She had no idea that exacerbated tinnitus might be a Covid-related problem until she learned otherwise on the website of the British Tinnitus Association, a co-sponsor of the Anglia Ruskin study.“I thought, ‘Thank God’ when I realized I wasn’t the only one out there,” she said. “I’ve met people through my work who don’t realize that there’s a medical term for the ringing in their ears. Just knowing that other people have the same condition is an enormous relief.”

Vaccinating health care workers resulted in an immediate and notable reduction of positive COVID-19 cases among employees, reducing the number of required isolations and quarantines by more than 90 percent, according to data at UT Southwestern Medical Center published in the New England Journal of Medicine.
Health care workers were among the first groups to be eligible for vaccination.
“Real-world experience with SARS-CoV-2 vaccination at UT Southwestern demonstrated a marked reduction in the incidence of infections among our employees, preserving the workforce when it was most needed,” notes Daniel K. Podolsky, M.D., president of UT Southwestern and senior author.
During the first 31 days of vaccinations becoming available, UT Southwestern provided a first dose to 59 percent of roughly 23,000 employees, while 30 percent were able to be fully vaccinated in that time frame. Among the findings: 1.5 percent became infected. Infection rates were highest — 2.6 percent — among nonvaccinated employees. Infection rates were lowest — .05 percent — among those fully vaccinated.”Our ability to quickly vaccinate a majority of our workforce in the midst of what became the largest surge to date in the region made a critical difference in ensuring we were able to continue providing top-flight care while health systems were strained,” says John Warner, M.D., executive vice president for health system affairs at UT Southwestern.
Researchers also saw advantages among partially vaccinated individuals, and from Jan. 9, the actual number of positive tests among all UT Southwestern employees was consistently lower than the number projected.
The data also show continued need to address vaccine hesitancy, with UT Southwestern now approaching 70 percent immunization among its workforce.
“In light of this real-world experience clearly demonstrating the effectiveness of immunization, further understanding of the reticence of some individuals to take advantage of vaccination bears even greater importance,” says first author William Daniel, M.D., vice president and chief quality officer at UT Southwestern.
UT Southwestern has provided educational outreach to community groups and businesses, developed extensive online resources including Q&As and blogs, and is preparing to launch a multilingual public service announcement campaign to help educate diverse communities about vaccination and address issues of hesitancy.
“It is important to reach out across multiple platforms to effectively address people’s questions so that we can continue to make progress on vaccine hesitancy,” says Marc Nivet, Ed.D., executive vice president for institutional advancement at UT Southwestern.
Dr. Daniel, professor of internal medicine, holds the William T. Solomon Professorship in Clinical Quality Improvement at UT Southwestern Medical Center. Dr. Nivet is associate professor of family and community medicine. Dr. Podolsky, professor of internal medicine, holds the Philip O’Bryan Montgomery, Jr., M.D. Distinguished Presidential Chair in Academic Administration and the Doris and Bryan Wildenthal Distinguished Chair in Medical Science. Dr. Warner, professor of internal medicine, holds the Nancy and Jeremy Halbreich, Susan and Theodore Strauss Professorship in Cardiology and the Jim and Norma Smith Distinguished Chair for Interventional Cardiology.
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Materials provided by UT Southwestern Medical Center. Note: Content may be edited for style and length.

Another step towards understanding Alzheimer’s disease has been taken at the Maisonneuve-Rosemont Hospital Research Centre. Molecular biologist Gilbert Bernier, and professor of neurosciences at Université de Montréal, has discovered a new function for the BMI1 gene, which is known to inhibit brain aging. The results of his work have just been published in Nature Communications.
In his laboratory, Bernier was able to establish that BMI1 was required to prevent the DNA of neurons from disorganizing in a particular way called G4 structures. This phenomenon occurs in the brains of people with Alzheimer’s disease, but not in healthy elderly people. Thus, BMI1 would protect against Alzheimer’s by preventing, among other things, the excessive formation of G4s that disrupt the functioning of neurons.
“This discovery adds to our knowledge of the fundamental mechanisms leading to Alzheimer’s,” said Bernier. “There is still no cure for this disease, which now affects nearly one million Canadians. Any advance in the field brings hope to all these people and their families.”
In previous articles published in the journals Cell Reports and Scientific Reports, Bernier demonstrated that the expression of the BMI1 gene is specifically reduced in the brains of people with Alzheimer’s disease. He also showed that inactivation of BMI1 in cultured human neurons or in mice was sufficient to recapitulate all the pathological markers associated with Alzheimer’s disease.
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Materials provided by University of Montreal. Note: Content may be edited for style and length.

Domestication has a consistent effect on the gut microbiota of animals and is similar to the effects of industrialisation in human populations, with ecological differences such as diet having a strong influence.
These findings, published today in eLife, highlight how the flexibility of the gut microbiota can help animals respond to ecological change and could help identify ways of manipulating gut microbial communities in the service of health.
Animals typically have complex communities of microbes living in their gut that can strongly influence functions such as immunity and metabolism. These communities can be extremely diverse and differ greatly between species and even individuals. We know, for instance, that domesticated animals, such as lab mice, have different gut microbial communities than their wild relatives. We have even seen large changes in the gut microbiota of industrialised human populations, some of which have been linked to the rise of certain diseases.
During domestication, animals experienced profound ecological changes that likely shaped their gut microbiota. “Domesticated animals and industrialised human populations potentially experienced similar ecological changes such as less diverse, more easily digestible diets, higher population densities, and more medical interventions,” explains first author Aspen Reese, who was a postdoctoral Junior Fellow in the Society of Fellows, Harvard University, US, at the time the study was carried out, and is now Assistant Professor at the University of California, San Diego, US. “We wanted to find out if domestication had consistent effects on the gut microbiota of animals and if the effects were indeed similar to those of industrialisation in humans.”
To assess the effects of domestication, the team sequenced and compared microbial DNA extracted from fecal samples of 18 species of wild and domesticated mammals. They found that domestication did have a clear global effect on gut microbiota, although the specific differences depended on the species.
Domestication involves strong selection pressure on animals, leading to important genetic and physiological changes that may also affect gut microbial communities. To unpack the relative roles of ecology and genetics, the team then swapped the diets of wild and domesticated animals. They found that the gut microbial communities of related animals, such as wolves and dogs, became much more similar to one another, supporting the idea that altered diets explain at least some of the changes in the gut microbiota seen with domestication.
To understand whether such differences also occur in humans, they then compared the gut microbial communities of humans to those of chimpanzees, one of our closest living relatives, and between humans living in industrialised versus non-industrialised populations. They found that differences between the gut microbiota of humans and chimpanzees were similar to those seen between domesticated and wild animals, with the largest changes evident in industrialised populations. Because all humans are equally related to chimpanzees, these results showed that ecological factors rather than genetics drive aspects of the gut microbiota shared between domesticated animals and humans living in industrialised populations.
“Our research highlights that the flexibility of the gut microbiota likely helps animals and humans respond to rapid ecological change,” concludes senior author Rachel Carmody, Assistant Professor in the Department of Human Evolutionary Biology at Harvard University. “But, at the same time, this flexibility can create opportunities for mismatch between the gut microbiota we have and the one our bodies have evolved to expect. As we increasingly appreciate the central role of the gut microbiota in biology, understanding the factors that shape it in animals and humans may help us identify new ways to improve experimental animal models, the wellbeing of animals we depend on, and ultimately, human health.”
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Materials provided by eLife. Note: Content may be edited for style and length.

An analysis of sex differences in the genetics of schizophrenia, bipolar disorder and major depressive disorders indicates that while there is substantial genetic overlap between males and females, there are noticeable sex-dependent differences in how genes related to the central nervous system, immune system, and blood vessels affect people with these disorders.
The findings, from a multinational consortium of psychiatric researchers including investigators and a senior author at Massachusetts General Hospital (MGH), could spur better treatments for major psychiatric disorders. They are published in the journal Biological Psychiatry.
The findings were made possible only through the cooperation of more than 100 investigators and research groups, who combed through the genomes of 33,403 people with schizophrenia, 19,924 with bipolar disorder, and 32,408 with major depressive disorder, as well as 109,946 controls (people without any of these diagnoses).
Their goal was to understand why these major psychiatric disorders differed between the sexes. For example, women have a significantly higher risk for major depressive disorder, whereas the risk for schizophrenia is significantly higher among men. The risk of bipolar disorder is about the same for both women and men, but disease onset, course, and prognosis differ markedly between the two.
“We’re in the era of Big Data, and we’re looking for genes that are associated with illnesses to identify druggable targets associated with the genotype, in order to develop more effective treatments for that illness that may differ by sex,” says senior author Jill M. Goldstein, PhD, founder and executive director of the Innovation Center on Sex Differences in Medicine (ICON) at MGH.
Goldstein and colleagues searched for clues in the form of single nucleotide polymorphisms, or SNPs (“snips”), in which a single DNA “letter” (nucleotide) differs from one person to the next and between sexes.
“There are sex differences in the frequency of chronic diseases and cancers as well. It’s pervasive,” says Goldstein, who is also a professor of Psychiatry and Medicine at Harvard Medical School. “But medicine, essentially, has been built on models of men’s health and male animals. We need to develop our precision medicine models incorporating the effect of sex.”
By taking advantage of large psychiatric databases, the investigators were able to demonstrate that the risks for schizophrenia, bipolar disorder and major depressive disorder are affected by interactions of specific genes with sex, apart from the effects of sex hormones such as estradiol or testosterone.
For example, the investigators found interactions with schizophrenia and depression and sex in genes controlling for the production of vascular endothelial growth factor, a protein that promotes the growth of new blood vessels.
“My lab is studying the substantial co-occurrence of depression and cardiovascular disease. It turns out that both depression and schizophrenia have a very high co-occurrence with cardiovascular disease. We believe there are shared causes between psychiatric and cardiovascular diseases that are not due to the effects of medication,” she says. “In addition, the co-occurrence of depression and cardiovascular disease is twice as high in women as in men, and this may, in part, be associated with our finding in depression of sex differences in a gene controlling vascular endothelial growth factor.”
The investigators emphasize that although the specific causes of the diseases they studied are still unknown, “our study underscores the importance of designing large-scale genetic studies that have the statistical power to test for interactions with sex. Dissecting the impact of sex, genes, and pathophysiology will identify potential targets for sex-dependent or sex-specific therapeutic interventions creating more effective therapies for both men and women,” she says.
The analyses were supported by private donor Gwill York, the National Institute of Mental Health and the NIH Office for Research on Women’s Health.