Publisher Health

The experimental antiviral drug MK-4482 significantly decreased levels of virus and disease damage in the lungs of hamsters treated for SARS-CoV-2 infection, according to a new study from National Institutes of Health scientists. SARS-CoV-2 is the virus that causes COVID-19. MK-4482, delivered orally, is now in human clinical trials. Remdesivir, an antiviral drug already approved by the U.S. Food and Drug Administration for use against COVID-19, must be provided intravenously, making its use primarily limited to clinical settings.
In their study, published in the journal Nature Communications, the scientists found MK-4482 treatment effective when provided up to 12 hours before or 12 hours after infecting the hamsters with SARS-CoV-2. These data suggest that MK-4482 treatment potentially could mitigate high-risk exposures to SARS-CoV-2, and might be used to treat established SARS-CoV-2 infection alone or possibly in combination with other agents.
The same research group, located at Rocky Mountain Laboratories, part of NIH’s National Institute of Allergy and Infectious Diseases in Hamilton, Montana, developed the hamster model last year to mimic SARS-CoV-2 infection and mild disease in people. The University of Plymouth in the United Kingdom collaborated on these most recent studies.
The project involved three groups of hamsters: a pre-infection treatment group; a post-infection treatment group; and an untreated control group. For the two treatment groups, scientists administered MK-4482 orally every 12 hours for three days. At the conclusion of the study, the animals in each of the treatment groups had 100 times less infectious virus in their lungs than the control group. Animals in the two treatment groups also had significantly fewer lesions in the lungs than the control group.
The scientists determined the MK-4482 treatment doses for this study based on previous experiments performed in mouse models of SARS-CoV-1 and MERS-CoV. In those studies, MK-4482 was effective at stopping the viruses from replicating.
With funding support from NIAID, Emory University’s Drug Innovation Ventures group in Atlanta developed MK-4482 (also known as molnupiravir and EIDD-2801) to treat influenza. Merck and Ridgeback Biotherapeutics are now jointly developing and evaluating MK-4482 as a potential COVID-19 treatment. The drug is in Phase 2 and 3 human clinical studies.
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Many long for a return to a post-pandemic “normal,” which, for some, may entail concerts, travel, and large gatherings. But how to keep safe amid these potential public health risks?
One possibility, according to a new study, is dogs. A proof-of-concept investigation published today in the journal PLOS ONE suggests that specially trained detection dogs can sniff out COVID-19-positive samples with 96% accuracy.
“This is not a simple thing we’re asking the dogs to do,” says Cynthia Otto, senior author on the work and director of the University of Pennsylvania School of Veterinary Medicine Working Dog Center. “Dogs have to be specific about detecting the odor of the infection, but they also have to generalize across the background odors of different people: men and women, adults and children, people of different ethnicities and geographies.”
In this initial study, researchers found the dogs could do that, but training must proceed with great care and, ideally, with many samples. The findings are feeding into another investigation that Otto and colleagues have dubbed “the T-shirt study,” in which dogs are being trained to discriminate between the odors of COVID-positive, -negative, and -vaccinated individuals based on the volatile organic compounds they leave on a T-shirt worn overnight.
“We are collecting many more samples in that study — hundreds or more — than we did in this first one, and are hopeful that will get the dogs closer to what they might encounter in a community setting,” Otto says.
Through the Working Dog Center, she and colleagues have had years of experience training medical-detection dogs, including those that can identify ovarian cancer. When the pandemic arrived, they leveraged that expertise to design a coronavirus detection study.

Some survivors of ebolavirus outbreaks make antibodies that can broadly neutralize these viruses — and now, scientists at Scripps Research have illuminated how these antibodies can disable the viruses so effectively. The insights may be helpful for developing effective therapies.
Ebolavirus is a family of often-deadly viruses that includes Ebola virus and many lesser-known viruses such as Bundibugyo virus, Sudan virus and Reston virus.
Structural biologists at Scripps Research used electron microscopy techniques to visualize a set of antibodies that target a key site on these viruses called the “glycan cap.” Their research showed that the antibodies work against ebolaviruses using the same three mechanisms to prevent the virus from infecting host cells.
The research, published in Cell Reports, is a step toward the creation of an antibody-based treatment that will be useful against a broad range of ebolaviruses.
“We now understand the molecular basis for these antibodies’ abilities to neutralize ebolviruses with broad reactivity against different viral species,” says the study’s first author Daniel Murin, PhD, a staff scientist in the laboratory of Andrew Ward, PhD.
Ward, a professor in the Department of Integrative Structural and Computational Biology at Scripps Research, says he hopes the work will contribute the development of a “cocktail” of therapeutic antibodies that can save lives by treating many forms of the Ebola virus.

A study published today in JAMA Internal Medicine shows that wearing two face coverings can nearly double the effectiveness of filtering out SARS-CoV-2-sized particles, preventing them from reaching the wearer’s nose and mouth and causing COVID-19. The reason for the enhanced filtration isn’t so much adding layers of cloth, but eliminating any gaps or poor-fitting areas of a mask.
“The medical procedure masks are designed to have very good filtration potential based on their material, but the way they fit our faces isn’t perfect,” said Emily Sickbert-Bennett, PhD, associate professor of infectious diseases at the UNC School of Medicine and lead author of the study.
To test the fitted filtration efficiency (FFE) of a range of masks, UNC researchers worked with James Samet, PhD, and colleagues in the USEPA Human Studies Facility on the campus of UNC-Chapel Hill. There they filled a 10-foot by 10-foot stainless-steel exposure chamber with small salt particle aerosols, and had researchers don combinations of masks to test how effective they were at keeping particles out of their breathing space.
Each individual mask or layered mask combination was fitted with a metal sample port, which was attached to tubing in the exposure chamber that measured the concentration of particles entering the breathing space underneath the researcher’s mask. A second tube measured the ambient concentration of particles in the chamber. By measuring particle concentration in the breathing space underneath the mask compared to that in the chamber, researchers determined the FFE.
“We also had the researchers in the chamber undergo a series of range-of-motion activities to simulate the typical motions a person may do throughout their day — bending at the waist, talking, and looking left, right, up and down,” said Phillip Clapp, PhD, an inhalation toxicologist in the UNC School of Medicine who has been testing mask FFE with Sickbert-Bennett since the pandemic began.
According to their findings, the baseline fitted filtration efficiency (FFE) of a mask differs person to person, due to each person’s unique face and mask fit. But generally, a procedure mask without altering the fit, is about 40-60% effective at keeping COVID-19-sized particles out. A cloth mask is about 40% effective.
Their recent findings on doubling of face masks, shows that when a cloth mask is placed over a surgical mask, the FFE improved by about 20%, and improved even more with a snug-fitting, sleeve-type mask, such as a gaiter. When layered over procedure masks, cloth masks improve fit by eliminating gaps and holding the procedure mask closer to the face, consistently covering the nose and mouth. When a procedure mask is worn over a cloth mask, FFE improved by 16%.
“We’ve found that wearing two loosely fitted masks will not give you the filtration benefit that one, snug-fitting procedure mask will,” Sickbert-Bennett said. “And with the current data supporting how effective mask-wearing is at preventing the spread of COVID-19, the best kind of double-masking is when you and the person you are interacting with are each correctly wearing a very snug-fitting mask.”
This study was partially funded by a grant from the Centers for Disease Control and Prevention (CDC), and expands upon research conducted by the agency earlier this year, which supported the CDC’s recommendation of double-masking to the public. Sickbert-Bennett and Clapp have previously discussed this recommendation and their research on the importance of mask fit with news outlets in a recorded conversation (https://news.unchealthcare.org/2021/02/unc-health-media-briefing-double-masking-importance-of-mask-fit/).
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Materials provided by University of North Carolina Health Care. Note: Content may be edited for style and length.

SARS-CoV-2, the virus that causes COVID-19, likely does not directly infect the brain but can still inflict significant neurological damage, according to a new study from neuropathologists, neurologists, and neuroradiologists at Columbia University Vagelos College of Physicians and Surgeons.
“There’s been considerable debate about whether this virus infects the brain, but we were unable to find any signs of virus inside brain cells of more than 40 COVID-19 patients,” says James E. Goldman, MD, PhD, professor of pathology & cell biology (in psychiatry), who led the study with Peter D. Canoll, MD, PhD, professor of pathology & cell biology, and Kiran T. Thakur, MD, the Winifred Mercer Pitkin Assistant Professor of Neurology.
“At the same time, we observed many pathological changes in these brains, which could explain why severely ill patients experience confusion and delirium and other serious neurological effects — and why those with mild cases may experience ‘brain fog’ for weeks and months.”
The study, published in the journal Brain, is the largest and most detailed COVID-19 brain autopsy report published to date, suggests that the neurological changes often seen in these patients may result from inflammation triggered by the virus in other parts of the body or in the brain’s blood vessels.
No Virus in Brain Cells
The study examined the brains of 41 patients with COVID-19 who succumbed to the disease during their hospitalization. The patients ranged in age from 38 to 97; about half had been intubated and all had lung damage caused by the virus. Many of the patients were of Hispanic ethnicity. There was a wide range of hospital length with some patients dying soon after arrival to the emergency room while others remained in the hospital for months. All of the patients had extensive clinical and laboratory investigations, and some had brain MRI and CT scans.

A person who owns a car or who has a college education may be less vulnerable to COVID-19, according to an analysis of cases in Tehran, Iran, one of the early epicenters of the pandemic. While such variables do not inherently lower a person’s risk, they do indicate an infrastructure of protection that persists despite how densely populated a person’s district might be.
The international collaboration published their results on April 3 in Sustainable Cities and Society.
“In the past few decades, there have been various efforts aimed at increasing urban density to enhance efficiency and contribute to climate change mitigation — but the COVID-19 pandemic has brought questions about the desirability of compact urban development to the forefront,” said paper author Ayyoob Sharifi, associate professor in the Graduate School of Humanities and Social Sciences and in the Graduate School of Advanced Science and Engineering at Hiroshima University. Sharifi is also affiliated with the Network for Education and Research on Peace and Sustainability.
Through a comprehensive data analysis from the early months of the pandemic (to April 4 and June 27, 2020), the researchers found that a population’s demographic structure — age, social and economic class, access to resources — is far more influential than simply how dense a population is. However, density is distinctly different than overcrowding for the resources available, the researchers said.
“We found that what drives the spread of infectious disease during a pandemic is overcrowding, which can occur in districts even with low density,” said paper author Amir Reza Khavarian-Garmsir, assistant professor in the Department of Geography and Urban Planning in the Faculty of Geographical Sciences and Planning at the University of Isfahan.
While a person less likely to be aware of or follow public health guidelines or more likely to use public transportation may be more at risk for the disease, the researchers didn’t find a statistically significant difference in urban districts with lower income and lower age compositions — indicating that age was one of the most significant risk factors for COVID-19 infection, despite density of living.
The data was obtained from Iran’s AC-19 app, which tracks positive cases and deaths by geographic location, the researchers assessed whether certain variables affected infection rates across the 22 districts and roughly 8.6 million residents of Tehran. They used structural equation modeling, which can use multiple factors to indicate the influence of unobservable variables, such as likelihood to follow public health recommendations, in combination with measurable factors, such as ease of access to medical facilities.
There are some drawbacks to the study, the researchers said, the main one of which is data availability and accuracy. The pandemic evolved so rapidly in the early months that tracking may not capture the full picture; and testing shortages and cost, as well as a relative lack of severe symptoms in children and young adults, may skew the number of true positive cases.
“It is perhaps too early to draw definitive conclusions, so future research should continue to investigate the relationship between urban density and transmission patterns of infectious disease,” Moradpour said.
The researchers said they hope their work will help policy makers develop guidelines to benefit all during urban and pandemic-preparedness planning.
“The next step is to further examine the impacts of urban density in other contexts,” Shafiri said. “In addition, we are trying to examine the long-term impacts of the pandemic on compact urban development policies.”
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A new study has shown that underweight and overweight women are at a significantly higher risk of experiencing recurrent miscarriages compared to those of average weight.
A research team led by the University of Southampton assessed the link between women’s lifestyle and risk of recurrent pregnancy loss, defined as women having two or more consecutive early miscarriages. The systematic review and meta-analysis study has been published in the journal Scientific Reports.
Miscarriage is the most common complication of early pregnancy, affecting 15 — 20% of all pregnancies. Recurrent pregnancy loss is a complex disease and although often attributed to numerous medical factors and lifestyle influences, the cause is deemed “unexplained” in around 50% of cases.
The results of this latest study found that there are higher occurrences of successive miscarriages in mothers who are underweight (having a Body Mass Index score of less than 18.5), overweight (having BMI between 25 and 30) and obese (having BMI above 30).
The study’s first author, Dr Bonnie Ng, MRC Fellow in Clinical and Experimental Sciences at the University of Southampton said, “Our study included sixteen studies and showed that being underweight or overweight significantly increases the risk of two consecutive pregnancy losses. For those with BMI greater than 25 and 30, their risk of suffering a further miscarriage increases by 20% and 70% respectively.’
The research team also set out to assess the impact of factors such as smoking and consumption of alcohol and caffeine. However they were unable to establish conclusively whether these have any impact or not due to inconsistencies of the results from a small number of studies and heterogeneity in women taking part in them.
Co-author Dr George Cherian, Specialist trainee in Obstetrics and Gynaecology, at Princess Anne Hospital, Southampton said, ‘while our study did not find any associations between recurrent pregnancy loss and lifestyle parameters such as smoking, alcohol and caffeine intake, further large-scale studies are required to clarify this.’
Whilst recognising that more observational and clinical research is needed to establish the full extent of lifestyle choices, the authors conclude that weight is a risk factor that can be modified to reduce the risk.
‘Our findings suggest that having an abnormal BMI exacerbates a woman’s risk of suffering from repeated miscarriages, and so clinicians really need to focus on helping women manage this risk factor’ concluded Ying Cheong, Professor of Reproductive Medicine at the University of Southampton and senior author of the paper.
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A candidate vaccine that could provide protection against the COVID-19 virus and other coronaviruses has shown promising results in early animal testing.
The candidate coronavirus vaccines, created by Virginia Tech’s University Distinguished Professor X.J. Meng and UVA Health’s Professor Steven L. Zeichner, prevented pigs from being becoming ill with a pig coronavirus, porcine epidemic diarrhea virus (PEDV).
The researchers have recently published their findings in the Proceedings of the National Academy of Sciences.
“The candidate vaccine was developed using an innovative vaccine platform targeting a highly conserved genomic region of coronaviruses,” said Meng, a University Distinguished Professor in the Department of Biomedical Sciences and Pathobiology in the Virginia-Maryland College of Veterinary Medicine. “The new vaccine platform utilizes a genome-reduced bacteria to express the coronavirus vaccine antigen on its surface. Such a vaccine platform can be manufactured with low cost in existing facilities around the world, which could meet the pandemic demand.”
Their coronavirus vaccine offers several advantages that could overcome major obstacles to global vaccination efforts. It would be easy to store and transport, even in remote areas of the world, and could be produced in mass quantities using existing vaccine-manufacturing factories.
“Our new platform offers a new route to rapidly produce vaccines at very low cost that can be manufactured in existing facilities around the world, which should be particularly helpful for pandemic response,” said Zeichner.

Working hours that deviate from an individual’s natural body clock are associated with greater cardiovascular risk, according to research presented at ESC Preventive Cardiology 2021, an online scientific congress of the European Society of Cardiology (ESC).
“Our study found that for each hour the work schedule was out of sync with an employee’s body clock, the risk of heart disease got worse,” said study author Dr. Sara Gamboa Madeira of the University of Lisbon, Portugal.
At least 20% of European employees work atypical hours or shifts,2 and growing scientific evidence associates these with deleterious cardiovascular outcomes.3 A number of explanations have been proposed, including sleep disruption and unhealthy behaviours. This study focused on the role of circadian misalignment, which is the difference between the “social clock” (e.g. work schedules) and the individual “biological clock.”
Dr. Gamboa Madeira explained: “We all have an internal biological clock which ranges from morning types (larks), who feel alert and productive in the early morning and sleepy in the evening, to late types (owls), for whom the opposite is true — with most of the population falling in between. Circadian misalignment occurs when there is a mismatch between what your body wants (e.g. to fall asleep at 10pm) and what your social obligations impose on you (e.g. work until midnight).”
The study included 301 blue collar workers, all performing manual picking activity in the distribution warehouses of a retail company in Portugal. Staff always worked either early morning (6am-3pm), late evening (3pm-midnight), or night (9pm-6am) shifts. Participants completed a questionnaire on sociodemographic factors (age, sex, education), occupational factors (work schedule, seniority), and lifestyle factors and had their blood pressure and cholesterol measured.
The Munich ChronoType Questionnaire was used to assess sleep duration, and to estimate each individual’s internal biological clock (also called chronotype). It was also used to quantify the amount of circadian misalignment (i.e. the mismatch between an individual’s biological clock and working hours) — referred to as social jetlag. Participants were divided into three groups according to hours of social jetlag: 2 hours or less, 2-4 hours, 4 hours or more.
The researchers used the European relative risk SCORE chart which incorporates smoking, blood pressure and cholesterol to calculate relative cardiovascular risk. Relative risk ranges from 1 (non-smoker with healthy blood pressure and cholesterol) to 12 (smoker with very high blood pressure and cholesterol). In this study, a relative risk of 3 or more was considered “high cardiovascular risk.” The researchers then investigated the association between social jetlag and high cardiovascular risk.
The average age of participants was 33 years and 56% were men. Just over half (51%) were smokers, 49% had high cholesterol, and 10% had hypertension. One in five (20%) were classified as high cardiovascular risk. Some 40% had a short sleep duration on workdays (6 hours or less). The average social jetlag was nearly 2 hours. In most workers (59%), social jetlag was 2 hours or less, while for 33% of staff it was 2-4 hours, and in 8% it was 4 hours or more.
A higher level of social jetlag was significantly associated with greater odds of being in the high cardiovascular risk group. The odds of being classified high cardiovascular risk increased by 31% for each additional hour of social jetlag, even after adjusting for sociodemographic, occupational, lifestyle, and sleep characteristics and body mass index.
Dr. Gamboa Madeira said: “These results add to the growing evidence that circadian misalignment may explain, at least in part, the association found between shift work and detrimental health outcomes. The findings suggest that staff with atypical work schedules may need closer monitoring for heart health. Longitudinal studies are needed to investigate whether late chronotypes cope better with late/night shifts and earlier chronotypes to early morning schedules, both psychologically and physiologically.”
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Materials provided by European Society of Cardiology. Note: Content may be edited for style and length.

COVID-19 needs no introduction. Last year, the disease, which is caused by the virus SARS-CoV-2, reached every continent across the globe. By the end of March 2021, there had been an estimated 128 million cases recorded with almost three million of these being fatal. As scientists’ race to develop vaccines and politicians coordinate their distribution, fundamental research on what makes this virus so successful is also being carried out.
Within the Mathematics, Mechanics, and Materials Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), postdoctoral researcher, Dr. Vikash Chaurasia, and Professor Eliot Fried have been using energy minimization techniques to look at charged proteins on biological particles. Previously they researched cholesterol molecules but when the pandemic hit, they realized that with the methods they had developed could be applied to the new virus. They collaborated with researchers Mona Kanso and Professor Jeffrey Giacomin, from Queen’s University in Canada, to take a close look at SARS-CoV-2 and see how the shape of the virus’ ‘spikes’ (which are officially called peplomers) aid its success at spreading so prolifically. Their study was recently published in Physics of Fluids.
“When one envisions a single coronavirus particle, it is common to think of a sphere with many spikes or smaller spheres distributed across its surface,” said Dr. Chaurasia. “This is the way the virus was originally modeled. But this model is a rough sketch and over the last year, we’ve come to learn much more about what the virus looks like.”
Instead, Dr. Chaurasia pointed out, the ‘spikes’ of the coronavirus particle are actually shaped like three small spheres stacked together to form a triangular shape. This is an important consideration because the shape of a viral particle can influence its ability to disperse.
To understand this, imagine a ball moving through space. The ball will follow a curve but, as it does this, it will also rotate. The speed at which the ball rotates is called its rotational diffusivity. A particle of SARS-CoV-2 moves in a similar way to this ball although its suspended in fluid (specifically, tiny droplets of saliva). The rotational diffusivity of the particle impacts how well it can align with and attach itself to objects (such as a person’s tissues or cells) and this has been key in its ability to successfully spread from person to person so quickly. A higher rotational diffusivity will mean that the particle shakes and jitters as it follows a trajectory — and thus may have difficulty attaching to objects or efficiently bouncing off an object to continue to move through the air. Whereas a lower rotational diffusivity has the opposite effect.
Another consideration was the charge of each spike. The researchers assumed that each is equally charged. The same charges always repel each other so if there are only two spikes on a particle and they have equal charges, they’ll be situated at either pole (as far away from each other as possible). As more equally charged spikes are added, they become evenly distributed across the surface of the sphere. This provided the researchers with a geometrical arrangement from which they could calculate the rotational diffusivity.
Previously, the researchers looked at a viral particle with 74 spikes. For this new study, they used the same particle but switched out the single-bead spikes for the three-bead triangles. When they did this, the rotational diffusivity of the particle was found to decrease by 39%. Moreover, this trend was found to continue with the addition of more spikes.
This was an important finding — having a lower rotational diffusivity means that the virus particles can better align and attach themselves to objects and people. Thus, this study suggests that the triangular shaped spikes have contributed to the success of SARS-CoV-2.
“We know it’s more complicated than this,” explained Dr. Chaurasia. “The spikes might not be equally charged. Or they might be flexible and able to twist themselves. Also, the ‘body’ of the particle might not be a sphere. So, we plan to do more research in this area.”
An additional interesting feature of this research is its connection to a question asked more than a century ago by physicist J. J. Thomson, who explored how a set number of charges will be distributed across a sphere.
“I find it fascinating that a problem considered more than 100 years ago has such relevance for the situation we’re in today,” said Professor Eliot Fried. “Although this question was first posed primarily from a standpoint of curiosity and intellectual interest, it has turned out to be applicable in unexpected ways. This shows why we mustn’t lose site of the importance of fundamental research.”
The scientists at OIST and at Queen’s University intend to continue to collaborate on this kind of research to shed light on the success of SARS-CoV-2. The researchers at Queen’s University have just been awarded a Mitacs Globalink Research Award to allow for lead author Mona Kanso to travel between Canada and Japan and work more closely with OIST.