Olafur Palsson, PsyD, professor of medicine in the UNC School of Medicine, led a study investigating the emotional and mental impact of the COVID-19 pandemic in the U.S. The study authors are releasing their findings directly to the public in an effort to provide guidance and understanding to individuals and clinicians as the pandemic evolves. Newswise — CHAPEL HILL, NC – The findings of a nationwide survey assessing the effects of the COVID-19 pandemic on the emotional wellbeing of the U.S. adult population have been released online. The survey was a collaboration between UNC School of Medicine and Harvard Medical School, and was quickly organized to gain an understanding of how individuals are responding to the stressors of isolation and quarantine, record unemployment levels, and the virus’ threat to their health. “We were very careful to balance the demographics and geographic distribution of survey respondents so that it is an accurate representation of the U.S., and essentially a snapshot of the population,” said principal investigator Olafur Palsson, PsyD, professor of medicine in the division of gastroenterology and hepatology in the UNC School of Medicine. The study consisted of a nationwide internet survey of 1,500 people conducted during the second half of May, when the pandemic was just beyond its peak in the nation. It is worth noting that the survey ended on May 30, five days after George Floyd was killed by a police officer in Minnesota. Nearly 90 percent of survey responses were collected before the movement across the U.S. to increase recognition of systemic racism. “We saw that levels of concern or worry differed among different demographics including age and race,” Palsson said. “Women and men tended to experience similar degrees of emotional impact associated with the pandemic on average, but younger people were more affected by it than older individuals, and the Hispanic population seemed to be the most impacted emotionally when comparing ethnic groups.” The study assessed a broad range of specific emotional effects related to the pandemic, and found that there were stressors that seemed to affect a majority of the population. Nearly 80 percent of respondents were frustrated on some level with not being able to do what they normally enjoy doing. Around the same number were worried about their own health, and nearly 90 percent of those surveyed were more worried about the health of loved ones than before the COVID-19 pandemic. “Most people have family or friends with chronic illness or health conditions that would make them more vulnerable to the virus, so worry about loved ones seems to be a shared feeling no matter who you are,” Palsson said. The emotional and mental impact of the pandemic could have long-term implications on well-being. Palsson and co-authors Sarah Ballou, PhD, instructor in medicine at Harvard Medical School and director of gastrointestinal psychology at Beth Israel Deaconess Medical Center, and Sarah Gray, PsyD, instructor in psychology at Harvard Medical School and practicing psychologist at Massachusetts General Hospital, wanted to get the results of the study out as quickly as possible to aid in addressing what could be a growing mental health crisis. “Understanding the psychological side of this pandemic has been somewhat neglected because there is so much else that is of concern right now,” Palsson said. “Our survey findings indicate that the anxiety and depression related to the emotional impact of these events are pushing more and more people into the clinical category of what is diagnosable as a mental health condition. We want people to seek the help they need.” A list of resources is available on the study’s website (http://pandemicimpactreport.com/index.html), along with a downloadable version of the study’s findings. Photo credit: UNC School of Medicine Olafur Palsson, PsyD
Newswise — TALLAHASSEE, Fla. — Social distancing during the COVID-19 pandemic has not led to an overall increase in loneliness among Americans. That’s the takeaway from a comprehensive, nationwide study by Florida State University College of Medicine researchers who surveyed more than 2,000 people before and during the enactment of stay-at-home policies in response to the COVID-19 pandemic. The study on how loneliness and perceived support has changed from before to during the pandemic is published in American Psychologist. “There has been a lot of worry that loneliness would increase dramatically because of the social distancing guidelines and restrictions,” said lead author Martina Luchetti, an assistant professor at the College of Medicine. “Contrary to this fear, we found that overall loneliness did not increase. Instead, people felt more supported by others than before the pandemic. Even while physically isolated, the feeling of increased social support and of being in this together may help limit increases in loneliness.” The paper is part of a larger study College of Medicine researchers are doing on COVID-19 to look at changes in mental health during the COVID-19 crisis and how psychological factors contribute to various aspects of response to the pandemic. The study involved a nationwide panel of adults ages 18 to 98. Participants first completed a survey in early February unrelated to COVID-19, before the virus was widely known to be a threat to the U.S. As the threat was being realized, researchers contacted participants again for two more surveys — one in mid-March during the 15-day period to slow the spread based on White House guidelines and another in late April as the guidelines were about to expire. More than 2,000 responses to the surveys were included in the findings. The study also looked for increased loneliness in specific at-risk groups, finding only modest evidence of a small increase in loneliness among older adults. Older adults reported less loneliness overall compared to younger age groups, despite an increase in loneliness during the acute phase of the outbreak. That increase in feelings of loneliness among older adults was temporary, leveling off after the issuance of stay-at-home orders. Individuals living alone and those with at least one chronic condition reported feeling lonelier at the outset but did not increase in loneliness after social-distancing measures were implemented. “Despite a small increase among some individuals, we found overall remarkable resilience in response to COVID-19,” said Angelina Sutin, associate professor of Behavioral Sciences and Social Medicine and senior author. Loneliness already was a known health risk before the pandemic, and it has been linked to increased risks of morbidity and mortality. Surveys have found that 35 percent of adults 45 and older report feeling lonely and 43 percent of those over 60 report experiencing loneliness at least some of the time. Some studies suggest that loneliness is even more pervasive among younger adults. “In the context of the coronavirus pandemic, it may be particularly difficult to reconnect with others given the restrictions on in-person social gatherings,” Luchetti said. “Even these transient feelings of loneliness can have a negative effect on health, meaning there could be dangerous unintended consequences if loneliness increases in response to the restrictive measures taken as a result of the pandemic.” Yet from the start of the pandemic, there have been anecdotal reports of people calling their family and friends more often and finding creative ways to stay connected. This outpouring of support may have shielded them from potential increases in loneliness. The pandemic is also something that everybody is going through. “Just knowing that you are not alone and that everyone is going through the same restrictions and difficulties may be enough in the short term to keep feelings of loneliness down,” Sutin said.
Study of over 900 U.S. metropolitan counties suggests that metropolitan size matters more than density in the spread of COVID-19 pandemic Newswise — A new study suggests that denser places, assumed by many to be more conducive to the spread of the coronavirus that causes COVID-19, are not linked to higher infection rates. The study, led by a researcher at the Johns Hopkins Bloomberg School of Public Health, also found that dense areas were associated with lower COVID-19 death rates. The study was published online June 18 in the Journal of the American Planning Association. For their analysis, the researchers examined SARS-CoV-2 infection rates and COVID-19 death rates in 913 metropolitan counties in the U.S. When other factors such as race and education were taken into account, the authors found that county density was not significantly associated with county infection rate. The authors also found that denser counties, as compared to more sprawling ones, tended to have lower death rates—possibly because they enjoyed a higher level of development including better health care systems. On the other hand, the authors found that higher coronavirus infection and COVID-19 mortality rates in counties are more related to the larger context of metropolitan size in which counties are located. Large metropolitan areas with a higher number of counties tightly linked together through economic, social, and commuting relationships are the most vulnerable to the pandemic outbreaks. “These findings suggest that urban planners should continue to practice and advocate for compact places rather than sprawling ones, due to the myriad well-established benefits of the former, including health benefits,” says study lead author Shima Hamidi, PhD, a Bloomberg Assistant Professor of American Health in Environmental Challenges in the Department of Environmental Health and Engineering at the Bloomberg School. Recent polls suggest that many Americans now consider an exodus from big cities likely, possibly due to the belief that more density equals more infection risk. Some government officials have posited that urban density is linked to the transmissibility of the virus. Hamidi, whose research background is in urban planning and architecture, and colleagues found otherwise. She and her colleagues, Sadegh Sabouri, a doctoral student, and Reid Ewing, Distinguished Professor of City and Metropolitan Planning at the University of Utah, examined data from January 20 through May 25 on 913 metropolitan U.S. counties, using an approach known as Structural Equation Modeling and taking into account factors such as population size, education levels, and demographic variables including age and race, and health care infrastructure such as ICU bed capacity. The researchers determined from this analysis that, when controlling for other factors, a measure of density that they termed the “activity density”—which takes into account both residents and workers in a given area—did not have a significant association with SARS-CoV-2 infection rates. Higher activity density did, however, have a significant association with COVID-19 death rates, but an unexpected one. "The fact that density is unrelated to confirmed virus infection rates and inversely related to confirmed COVID-19 death rates is important, unexpected, and profound,” says Hamidi. “It counters a narrative that, absent data and analysis, would challenge the foundation of modern cities and could lead to a population shift from urban centers to suburban and exurban areas." The analysis found that after controlling for factors such as metropolitan size, education, race, and age, doubling the activity density was associated with an 11.3 percent lower death rate. The authors say that this is possibly due to a faster and more widespread adoption of social distancing practices and better quality of health care in areas of denser population. The authors conclude that a higher county population, a higher proportion of people age 60 and up, a lower proportion of college-educated people, and a higher proportion of African Americans were all associated with a greater infection rate and mortality rate. The researchers have been updating the data as the pandemic progresses, and are finding that the associations they have uncovered are becoming even stronger, Hamidi says. The team is also conducting a longitudinal study that tracks the relationships among density, the county-level SARS-CoV-2 infection rates and mortality rates, and explanatory factors as they change over time, and have found consistent results regarding the inverse relationship between density and the COVID-19 mortality rate. “Does Density Aggravate the COVID-19 Pandemic? Early Results and Lessons for Planners” was written by Shima Hamidi, Sadegh Sabouri, and Reid Ewing.
UT Southwestern Medical Center Diffusion tractography uses the movement of water molecules to identify tracts that connect different parts of the brain. It can be used to pinpoint the part of the thalamus to treat with focused ultrasound. DALLAS – June 14, 2020 – Recently developed MRI techniques used to more precisely target a small area in the brain linked to Parkinson’s disease and essential tremor may lead to better outcomes without surgery and with less risk of negative effects, a new study led by UT Southwestern researchers suggests. The study, published today in Brain, describes recently refined MRI methods designed to allow neuroradiologists to zero in on a pea-sized region in the brain’s thalamus involved in movement. Using the images, doctors then can use high-intensity focused ultrasound (HIFU) to ablate, or burn away, problem tissue, says Bhavya R. Shah, M.D., first author of the study and an assistant professor of radiology and neurological surgery at UT Southwestern’s Peter O’Donnell Jr. Brain Institute. “The benefit for patients is that we will be better able to target the brain structures that we want,” Shah says. “And because we’re not hitting the wrong target, we’ll have fewer adverse effects.” The procedures are already Food and Drug Administration-approved for use in patients, and UTSW plans to begin employing them to treat patients when its Neuro High Intensity Focused Ultrasound Program opens this fall. Adverse effects from imprecise targeting include problems walking or slurring words. While such effects are usually temporary, they can be permanent in 15 to 20 percent of cases, says Dr. Shah. According to the National Institutes of Health, essential tremor affects up to 10 million Americans and Parkinson’s disease impacts more than 1 million. Both are neurologic diseases thought to have genetic links. The first line of treatment for the involuntary trembling or shaking seen with these diseases is medication. However, approximately 30 percent of patients do not respond well to drugs, according to the study. In the late 1990s, neurosurgeons began using a procedure called deep brain stimulation, opening the skull to permanently implant metal electrodes that could then be stimulated via a battery pack. About a decade ago, a new MRI-guided procedure emerged that uses high-intensity ultrasound waves to heat and eliminate a small section of the thalamus linked to the disorders. MRI-guided HIFU is currently approved for treatment of essential tremor and tremors seen in Parkinson’s disease patients. The outpatient procedure does not require opening the skull, and the patient is awake while it is performed, says Dr. Shah. “No cuts. No anesthesia. No implanted devices.” A challenge in both procedures has been locating the precise area inside the brain’s thalamus to treat – the pea-sized ventral intermediate nucleus, says Dr. Shah. Traditionally, doctors have relied on either landmarks or maps of the brain drawn from cadavers to help them pinpoint the correct location. However, every brain is different, Dr. Shah says, and tiny errors can lead to damage in surrounding tissue, or to missing portions of the correct target. Three newly refined MRI techniques are better at delineating the target tissue, according to the study. The most widely studied and perhaps most promising imaging method is called diffusion tractography, says Dr. Shah. It creates precise brain images by taking into account the natural water movement within tissues. The other methods described are quantitative susceptibility mapping – which creates contrast in the image by detecting distortions in the magnetic field caused by substances such as iron or blood – and fast gray matter acquisition TI inversion recovery – which operates much like a photo negative, turning the brain’s white matter dark and its gray matter white in order to provide greater detail in the gray matter. Dr. Shah and his team plan to participate in a multicenter clinical trial with collaborators at the Mayo Clinic in Rochester, Minnesota, testing the diffusion tractography method in patients. Senior author of the study was Rajiv Chopra, Ph.D., director of image-guided therapy development and associate professor of radiology in the Advanced Imaging Research Center at UTSW. Researchers at the Mayo Clinic also participated in the study.
ATS Drug shortages exacerbated by COVID-19. Newswise — June 11, 2020─ A new paper published online in the Annals of the American Thoracic Society examines the nation’s current shortage of vitally needed medications, and how this dangerous situation is being made worse by the COVID-19 pandemic. The authors provide recommendations on how clinicians and institutions might address potential scarcities of essential medications during the current public health crisis. In “Preparing for COVID-19 Related Drug Shortages,” Andrew G. Shuman, MD, and co-authors discuss how the federal and state governments, as well as health care providers, need to develop ethically sound policies that address already perilously low supplies of certain commonly-used medications, which are dwindling further due to resources needed to combat COVID-19. “It is critical that these conversations occur now due to current shortages, as well as the necessary lead time to plan for future shortages,” said Dr. Shuman, co-chief of the Clinical Ethics Service, Center for Bioethics and Social Sciences in Medicine, University of Michigan Medical School. “Drug shortages have been a national emergency for years and are currently exacerbated due to COVID-19. Issues related to supply chain and anticipated increased ICU needs over the course of the pandemic are worsening the problem.” Yoram Unguru, MD, MS, MA, a physician-ethicist at The Herman and Walter Samuelson Children’s Hospital at Sinai and Johns Hopkins Berman Institute of Bioethics, who is a co-author of the paper, added, “As of today the American Society of Health-system Pharmacists (ASHP) reports 213 drugs shortages in the United States. It is not just patients with COVID-19 who are affected. One example of a current drug with a critically short supply is Erwinia asparaginase, a life-saving chemotherapeutic agent for both children and adults with cancer.” Among medical specialties severely affected are oncology, critical care and infectious disease. The authors stated that regional communication among hospitals is an important first step — helping determine how local drug supply chains are affected — and that coordination and sharing mechanisms are also critical. This information sharing would ideally occur via a central repository or clearinghouse. Both the FDA and ASHP also maintain databases of current drug shortages, and independent health care companies maintain their own databases that can provide invaluable information. “Sharing information is an important first step,” the authors stated. “The second and more difficult step involves actual sharing of medications among hospitals and health systems.” There are a number of barriers to this taking place, among others, the need for cooperation among competing health systems, concerns about potential liability, and legal regulations that affect the transfer of drugs. Erin Fox, PharmD, a co-author who is director of drug information and support services for Utah Health noted, “Tantamount to this effort is facilitating communication between pharmacists — those tasked with maintaining supplies, as well as those embedded within clinical teams — in order to inform the clinical team how supply may impact care delivery.” She continued, “Pandemic-era strategies for conservation of commonly used critical care agents at risk of shortages should be noted, recognizing that these shortages are often regional and unpredictable, and intensive care protocols and strategies are highly individualized.” A list of these commonly used drugs is included in the paper. The authors noted that communication should not be limited to discussions among pharmacists, hospitals, and health systems. Open discussions with patients who are most affected by drug shortages are essential. In the spirit of openness, the authors recommended that hospitals consider publicly posting information about drug shortages. Dr. Shuman and colleagues called upon stakeholders, from governments to clinicians, to refocus some of their efforts in managing shortages of ventilators during the COVID-19 crisis to develop workflows and rationing criteria for essential medicines. “Even if there are sufficient ventilators, a critical shortage of sedatives, paralytics and/or opioids will obviate the ability to keep patients safely intubated. Data suggest that these shortages have already been associated with inadvertent extubations.” The authors have also identified hoarding of drugs thought to be potential COVID treatments as a problem. “Once effective treatments and/or vaccines for COVID-19 are available, prioritizing nascent supplies will present a formidable challenge,” they predicted. “In the coming days and months, this matter demands global attention. Only with clear lines of communication and a proactive, collaborative approach can we weather this impending storm.”
Newswise — Population-wide use of facemasks keeps the coronavirus ‘reproduction number’ under 1.0, and prevents further waves of the virus when combined with lockdowns, a modelling study from the universities of Cambridge and Greenwich suggests. The research suggests that lockdowns alone will not stop the resurgence of SARS-CoV-2, and that even homemade masks with limited effectiveness can dramatically reduce transmission rates if worn by enough people, regardless of whether they show symptoms. The researchers call for information campaigns across wealthy and developing nations alike that appeal to our altruistic side: “my facemask protects you, your facemask protects me”. The findings are published in the Proceedings of the Royal Society A. “Our analyses support the immediate and universal adoption of facemasks by the public,” said lead author, Dr Richard Stutt, part of a team that usually models the spread of crop diseases at Cambridge’s Department of Plant Sciences. “If widespread facemask use by the public is combined with physical distancing and some lockdown, it may offer an acceptable way of managing the pandemic and re-opening economic activity long before there is a working vaccine.” Dr Renata Retkute, coauthor and Cambridge team member, said: “The UK government can help by issuing clear instructions on how to make and safely use homemade masks.” “We have little to lose from the widespread adoption of facemasks, but the gains could be significant.” The new coronavirus is transmitted through airborne droplets loaded with SARS-CoV-2 particles that get exhaled by infectious people, particularly when talking, coughing or sneezing. For the latest study, Cambridge researchers worked to link the dynamics of spread between individuals with population-level models, to assess different scenarios of facemask adoption combined with periods of lockdown. The modelling included stages of infection and transmission via surfaces as well as air. Researchers also considered negative aspects of mask use, such as increased face touching. The reproduction or ‘R’ number – the number of people an infected individual passes the virus onto – needs to stay below 1.0 for the pandemic to slow. The study found that if people wear masks whenever they are in public it is twice as effective at reducing ‘R’ than if masks are only worn after symptoms appear. In all modelling scenarios, routine facemask use by 50% or more of the population reduced COVID-19 spread to an R less than 1.0, flattening future disease waves and allowing less-stringent lockdowns. Viral spread reduced further as more people adopted masks when in public. 100% mask adoption combined with on/off lockdowns prevented any further disease resurgence for the 18 months required for a possible vaccine. The models suggest that – while the sooner the better – a policy of total facemask adoption can still prevent a second wave even if it isn’t instigated until 120 days after an epidemic begins (defined as the first 100 cases). The team investigated the varying effectiveness of facemasks. Previous research shows that even homemade masks made from cotton t-shirts or dishcloths can prove 90% effective at preventing transmission. The study suggests that an entire population wearing masks of just 75% effectiveness can bring a very high ‘R’ number of 4.0 – the UK was close to this before lockdown – all the way down to under 1.0, even without aid of lockdowns. In fact, masks that only capture a mere 50% of exhaled droplets would still provide a “population-level benefit”, even if they quadrupled the wearer’s own contamination risk through frequent face touching and mask adjustment (a highly unlikely scenario). The researchers point out that crude homemade masks primarily reduce disease spread by catching the wearer’s own virus particles, breathed directly into fabric, whereas inhaled air is often sucked in around the exposed sides of the mask. “There is a common perception that wearing a facemask means you consider others a danger,” said Professor John Colvin, coauthor from the University of Greenwich. “In fact, by wearing a mask you are primarily protecting others from yourself.” “Cultural and even political issues may stop people wearing facemasks, so the message needs to be clear: my mask protects you, your mask protects me.” “In the UK, the approach to facemasks should go further than just public transport. The most effective way to restart daily life is to encourage everyone to wear some kind of mask whenever they are in public,” Colvin said. Prof Chris Gilligan, coauthor from Cambridge’s Epidemiology and Modelling Group in the Department of Plant Sciences, added: “These messages will be vital if the disease takes hold in the developing world, where large numbers of people are resource poor, but homemade masks are a cheap and effective technology.”
Newswise — The country’s first convalescent plasma transfusion trial results have been peer-reviewed and published, showing 19 out of 25 patients improving with the treatment and 11 discharged from the hospital. On March 28, Houston Methodist became the first academic medical center in the nation to transfuse plasma from recovered COVID-19 patients into two critically ill patients. With no adverse side effects caused by the plasma transfusion, the study concluded that convalescent plasma is a safe treatment option for patients with severe COVID-19 disease. To date, this is the largest cohort worldwide assessed for outcomes pertaining to convalescent plasma transfusion for COVID-19. The findings are described in a paper appearing in press May 26 (online May 28) in The American Journal of Pathology. This is the first peer-reviewed publication on convalescent plasma use in the U.S. James M. Musser, M.D., Ph.D., chair of the Department of Pathology and Genomic Medicine at Houston Methodist, is the corresponding author on the study, titled “Treatment of COVID-19 patients with convalescent plasma.” Eric Salazar, M.D., Ph.D., assistant professor of pathology and genomic medicine with the Houston Methodist Research Institute, is the principal investigator who led the project to treat critically ill COVID-19 patients with convalescent plasma. “While physician scientists around the world scrambled to test new drugs and treatments against the COVID-19 virus, convalescent serum therapy emerged as potentially one of the most promising strategies,” Musser said. “With no proven treatments or cures for COVID-19 patients, now was the time in our history to move ahead rapidly.” Patients were first treated under emergency use guidelines (eIND) from the U.S. Food and Drug Administration and then received approval April 3 from the FDA to open up the trial to more patients as an investigational new drug (IND). This extraordinarily rapid approval granted by the FDA opened up access to convalescent plasma treatment for COVID-19 patients. The century-old therapeutic approach dates back to at least as early as 1918 to fight the Spanish Flu and more recently was used with some success during the 2003 SARS pandemic, the 2009 influenza H1N1 pandemic and the 2015 Ebola outbreak in Africa. Following a study early on in the COVID-19 pandemic, where a handful of critically ill patients in China showed improvement, an interdisciplinary team of Houston Methodist physician scientists and health care workers rapidly targeted the COVID-19 virus with convalescent serum therapy. Additional findings during this trial revealed patient outcomes following plasma therapy were very similar to recently published results of patients treated on a compassionate-use basis with the antiviral drug remdesivir. The research team also concluded that any observed complications were consistent with findings reported for COVID-19 disease progression and did not result from the plasma transfusions. The study’s overall findings were consistent with several other small case studies of convalescent plasma use for severe COVID-19 that have been recently reported. Ultimately, although the convalescent plasma therapy administered on the front lines at Houston Methodist was implemented for emergency treatment, the study’s authors recognize the important need for controlled clinical trials to determine its therapeutic efficacy. A randomized controlled trial is currently being considered at Houston Methodist where they would also look more closely at variables such as timing of the transfusion after the onset of symptoms, the number and volume of transfusions adjusted for patient biometrics, antibody levels in donor plasma and numerous other parameters needed to effectively evaluate how to optimize this therapy. This would help address some questions, including whether patients would have better outcomes if plasma transfusions were administered sooner after the onset of symptoms. Not all plasma recipients transfused so far at Houston Methodist were part of this first trial. Since late March, when the first patients were infused with convalescent plasma, Houston Methodist has treated 74 critically ill COVID-19 patients, 50 of whom have been discharged from the hospital and are recovering. More than 150 recovered COVID-19-infected individuals donated their plasma, many of them continuing to do so frequently. AJP, an Elsevier journal, is the official journal of the American Society for Investigative Pathology and publishes high-quality original research reports, reviews and commentaries related to the molecular and cellular basis of disease. In addition to Musser and Salazar, other collaborators on this study were Katherine K. Perez, Madiha Ashraf, Jian Chen, Brian Castillo, Paul C. Christensen, Taryn Eubank, David W. Bernard, Todd Eagar, S. Wesley Long, Sishir Subedi, Randall J. Olsen, Christopher Leveque, Mary R. Schwartz, Monisha Dey, Cheryl Chavez-East, John Rogers, Ahmed Shehabeldin, David Joseph, Guy Williams, Karen Thomas, Faisal Masud, Christina Talley, Katharine G. Dlouhy, Bevin Lopez, Curt Hampton, Jason Lavinder, Jimmy D. Gollihar, Andre C. Maranhao, Gregory C. Ippolito, Matthew Ojeda Saavedra, Concepcion C. Cantu, Prasanti Yerramilli and Layne Pruitt. This study was supported by funding from the National Institutes of Health (grants AI146771-01 and AI139369-01), the Fondren Foundation, the National Institute of Allergy and Infectious Diseases (Contract Number 75N93019C00050), the Army Research Office (Cooperative Agreement W911NF-12-1-0390), Houston Methodist Infectious Diseases Research Fund, Houston Methodist Hospital and Houston Methodist Research Institute. Photo: Houston Methodist Houston Methodist physician scientists (left to right) Eric Salazar, MD, PhD, and James M. Musser, MD, PhD, discuss their convalescent plasma trial for treating COVID-19, the results of which were the first in the U.S. to be peer-reviewed and published.
Newswise — LA JOLLA—Every year, more than 68,000 people end up with a clinical case of Japanese encephalitis. One in four of these patients will die. The mosquito-borne virus, which is most common in Southeast Asia, also causes severe neurological damage and psychiatric disorders. There is no cure for Japanese encephalitis, but there are effective vaccines against Japanese encephalitis virus (JEV). The problem is that JEV’s range is spreading, and more and more people at risk of the disease also live in areas where viruses like Zika are prevalent. In a new study, published June 5, 2020, in the Journal of Experimental Medicine, scientists at La Jolla Institute for Immunology (LJI) shows that antibodies against JEV are “cross-reactive” and can also recognize Zika virus. Unfortunately, these antibodies can actually make Zika cases more severe. The research, conducted in mice, is the first to show that T cells can counteract this dangerous phenomenon. “This means we probably need to be developing a vaccine against both viruses that can elicit a good balance of antibodies and T cells,” says Associate Professor Sujan Shresta, Ph.D., who co-led the study in collaboration with Jinsheng Wen, Ph.D., of Ningbo University and Wenzhou Medical University, and Yanjun Zhang, Ph.D., of Zhejiang Provincial Center for Disease Control and Prevention. Shresta has spent much of her career studying flaviruses, a family of viruses which includes Zika, JEV, dengue, West Nile virus and yellow fever. These diseases have spread in recent years as more people around the world have moved to cities and climate change has allowed the mosquitoes that carry these diseases to expand their habitat. People in many countries now live at risk of encountering multiple harmful flaviviruses in their lives. “The immune responses to these viruses are very cross-reactive,” says Shresta. “The problem is that the immune response can be both good and bad.” In some cases, antibodies against one flavivirus can make a future flavivirus infection even worse by allowing the virus to enter host cells. Shresta and investigators worldwide have shown this process, called antibody-dependent enhancement (ADE), during Zika and dengue infections in animal models that recapitulate severe dengue or Zika disease in individuals with prior exposure to dengue or Zika virus. However, ADE of Zika disease in cases of previous JEV exposure, and the interplay between antibodies and infection-fighting immune cells called CD8+ T cells, had not been studied before. For the new study, Shresta and her colleagues took antibodies from JEV-infected mice or JEV-vaccinated people and injected them into healthy mice. The healthy mice were then exposed to Zika virus. These mice experienced ADE and had far more severe cases of Zika fever than mice with no antibodies against JEV. Shresta and her colleagues next focused their attention on CD8+ T cells from JEV-infected mice. They found that CD8+ T cells primed to fight JEV could counteract the harmful effects of cross-reactive antibodies. “These JEV-elicited T cells were indeed able to recognize and get rid of the Zika virus infection,” says Shresta. In short, the mouse survival rate went up and their viral load went down, thanks to the CD8+ T cells. A future JEV vaccine would need to prompt a similar response from CD8+ T cells to help a person avoid ADE of Zika infection. Shresta says this work can help shed light on how to fight the whole family of flaviviruses, which includes over 70 different species, and many countries are increasingly dealing with cocirculation of multiple flaviviruses. “Any of these viruses could cause a major, major outbreak,” says Shresta. “We need to look at deploying a combination Zika/JEV vaccine, and we may need to tailor vaccines to particular locations where we know both JEV and Zika pose a threat.” Shresta adds that research into cross-reactive antibodies and T cell responses is especially important today as scientists investigate whether exposure to common cold coronaviruses can leave a person with any immunity against SARS-CoV-2, the novel coronavirus. “This provides us with a really good model to learn about immune response,” Shresta says. The study, titled, “Japanese encephalitis virus-primed CD8+ T cells prevent antibody-dependent enhancement of Zika virus pathogenesis,” was supported by the K.C. Wong Magna Fund of Ningbo University, the Zhejiang Provincial Natural Science Foundation (LY17C010004), the National Natural Science Foundation of China (31870159) and institutional funds from the La Jolla Institute for Immunology. Additional authors included Zhiliang Duan, Wenhua Zhou, Weiwei Zou, Shengwei Jin, Dezhou Li, Xinyu Chen, Yongchao Zhou, Lan Yang and Yanjun Zhang. DOI: 10.1084/jem.20192152
Newswise — Hamilton, ON (June 1, 2020) – A comprehensive review of existing evidence supports physical distancing of two metres or more to prevent person-to-person transmission of COVID-19, says an international team led by McMaster University and St. Joseph’s Healthcare Hamilton. Face masks and eye protection decrease the risk of infection, too. The systematic review and meta-analysis was commissioned by the World Health Organization. The findings were published today in The Lancet. “Physical distancing likely results in a large reduction of COVID-19,” said lead author Holger Schünemann, professor of the departments of health research methods, evidence, and impact, and medicine at McMaster. Schünemann is co-director of the World Health Organization (WHO) Collaborating Centre for Infectious Diseases, Research Methods and Recommendations. He also is director of Cochrane Canada and McMaster GRADE Centre. “Although the direct evidence is limited, the use of masks in the community provides protection, and possibly N95 or similar respirators worn by health-care workers suggest greater protection than other face masks,” Schünemann said. “Availability and feasibility and other contextual factors will probably influence recommendations that organizations develop about their use. Eye protection may provide additional benefits.” The systematic review was conducted by a large, international collaborative of researchers, front-line and specialist clinicians, epidemiologists, patients, public health and health policy experts of published and unpublished literature in any language. They sought direct evidence on COVID-19 and indirect evidence on related coronaviruses causative of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The team used Cochrane methods and the Grading of Recommendations, Assessment, and Evaluation (GRADE) approach which is used world-wide to assess the certainty of evidence. They identified no randomized control trials addressing the three coronaviruses but 44 relevant comparative studies in health-care and non-health-care (community) settings across 16 countries and six continents from inception to early May 2020. The authors noted more global, collaborative, well-conducted studies of different personal protective strategies are needed. For masks, large randomized trials are underway and are urgently needed. The scientific lead is Derek Chu, a clinician scientist in the departments of health research methods, evidence, and impact, and medicine at McMaster and an affiliate of the Research Institute of St. Joe's Hamilton. “There is an urgent need for all caregivers in health-care settings and non-health-care settings to have equitable access to these simple personal protective measures, which means scaling up production and consideration about repurposing manufacturing,” said Chu. “However, although distancing, face masks, and eye protection were each highly protective, none made individuals totally impervious from infection and so, basic measures such as hand hygiene are also essential to curtail the current COVID-19 pandemic and future waves.” The work was funded by the World Health Organization and involved close collaboration with the American University of Beirut, Lebanon and many international partners. Photo credit: by Gerli Sirk Caption: Holger Schünemann is a professor of the departments of health research methods, evidence, and impact, and medicine at McMaster. He is also co-director of the World Health Organization (WHO) Collaborating Centre for Infectious Diseases, Research Methods and Recommendations.
Tokyo, Jun 1, 2020 A team of scientists from Japan recently achieved more efficient degradation of the human serum albumin protein—an important protein in the blood—via high-intensity infrared irradiation, by attaching a zinc metal complex to the protein. Their findings indicate potential for future application of certain metal complexes to therapeutic interventions for diseases such as Alzheimer’s. Artificial metalloenzymes are hybrid compounds that are synthesized by attaching metal complexes to protein molecules. In the past few years, these compounds have garnered considerable attention in research communities because of their applicability as bio-inspired catalysts, in biofuel cells, and in therapeutic interventions such as targeted protein degradation and drug delivery. Advancing research on their application in targeted protein degradation, a team of scientists from the Tokyo University of Science, Japan, and Universidad Complutense de Madrid, Spain, examined the degradation of a specific metalloenzyme upon irradiation with high-energy infrared radiation. This metalloenzyme was one they had created by attaching a zinc metal complex (ZnL) to human serum albumin (HSA). The use of high-energy infrared radiation to degrade proteins is not new. For instance, a previous study at the Tokyo University of Science used this technique to degrade several protein aggregates, including the protein aggregate whose buildup between neurons in the brain, called amyloid plaque, causes Alzheimer’s disease. What the present study finds, as Dr Takashiro Akitsu, lead scientist, explains, is that “when human serum albumin is conjugated with a zinc complex, protein damage is promoted upon irradiation with a mid-infrared free-electron laser.” A mid-infrared free-electron laser (IR-FEL) is the instrument that the scientists used to irradiate the hybrid. The team of scientists comprising Prof Akitsu, Prof Koichi Tsukiyama, Dr Takayasu Kawasaki, and Assistant Prof Tomoyuki Haraguchi, among others, from Japan and Prof Mauricio A. Palafox from Complutense de Madrid, Spain, first used infrared (IR) spectroscopy to verify the attachment of ZnL to HSA. The IR spectra they obtained also indicated the optimal wavelengths for degradation: these were 1537, 1652, and 1622 cm-1, corresponding to the two amide bonds in HSA and the carbon-nitrogen double bond of ZnL, respectively. The scientists created thin films of both the HSA and the HSA+ZnL hybrid and irradiated targeted portions of these films. They then compared the radiation damage caused by IR-FEL irradiation to the films, using a technique called Fourier transform infrared (FT-IR) microscopy and a program to evaluate changes in the protein secondary structure, called IR-SSE. At 1622 cm-1, the HSA+ZnL hybrid structure did not dissociate. But, at the other two wavelengths, the protein structure of HSA, in both the pure HSA and hybrid forms, appeared significantly damaged. Further, in the latter cases, the hybrid compound was more degraded than pure HSA was. The scientists believe that the attachment of ZnL to the HSA protein destabilized the protein structure, allowing it to degrade more easily. Overall, this attachment of ZnL was feasible and assisted the degradation of the protein instead of alleviating it. These results are presented in a paper published in the International Journal of Molecular Sciences, in which the scientists highlight that “at present, the exact binding mechanism between the complex and the protein is unknown.” Further, Prof Akitsu clarifies that “research on various protein-metal complex pairs is ongoing.” The findings of this study cannot yet be generalized and until scientists have better insights, the applications of such metal complex-protein hybrids in therapeutic interventions or other areas of biotechnology will remain limited. Nevertheless, this study, in addition to the previous studies conducted at the Tokyo University of Science in this field, certainly makes us hopeful of a future in which diseases that involve protein defects, such as Alzheimer’s, are curable. *** Reference Title of original paper: Degradation of Human Serum Albumin by Infrared Free Electron Laser Enhanced by Inclusion of a Salen-Type Schiff Base Zn (II) Complex Journal: International Journal of Molecular Sciences DOI: 10.3390/ijms21030874 About the Tokyo University of Science Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan's development in science through inculcating the love for science in researchers, technicians, and educators. With a mission of “Creating science and technology for the harmonious development of nature, human beings, and society", TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today's most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field. Website: https://www.tus.ac.jp/en/mediarelations/ About Prof Takashiro Akitsu from the Tokyo University of Science Takashiro Akitsu is a Professor at the Faculty of Science at Tokyo University of Science. As an active researcher in the field of inorganic chemistry, he focuses particularly on coordination chemistry and materials science. He has a PhD from Osaka University, having focused his post-graduate research on coordination, crystal and bioinorganic chemistry. He was named Professor of the Year in 2018 for his teaching work on biomaterials, and holds a patent for an ultraviolet absorber since 2016. Funding information This research was supported by the Japanese Ministry of Education, Culture, Sports, Science and Technology, under the Photon Beam Platform Project.