Publisher Health

Scientists examining the remains of 36 bubonic plague victims from a 16th century mass grave in Germany have found the first evidence that evolutionary adaptive processes, driven by the disease, may have conferred immunity on later generations of people from the region.
“We found that innate immune markers increased in frequency in modern people from the town compared to plague victims,” said the study’s joint-senior author Paul Norman, PhD, associate professor in the Division of Personalized Medicine at the University of Colorado School of Medicine. “This suggests these markers might have evolved to resist the plague.”
The study, done in conjunction with the Max Planck Institute in Germany, was published online Thursday in the journal Molecular Biology and Evolution.
The researchers collected DNA samples from the inner ear bones of individuals in a mass grave in the southern German city of Ellwangen which experienced bubonic plague outbreaks in the 16th and 17th centuries. Then they took DNA samples from 50 current residents of the town.
They compared their frequency spectra — the distribution of gene variants in a given sample — for a large panel of immunity-related genes.
Among the current inhabitants, the team found evidence that a pathogen, likely Yersinia pestis which causes bubonic plague, prompted changes in the allele distribution for two innate pattern-recognition receptors and four Human Leukocyte Antigen molecules, which help initiate and direct immune response to infection. An allele is a variant form of a gene.

An artificial intelligence (AI) program accurately predicts the risk that lung nodules detected on screening CT will become cancerous, according to a study published in the journal Radiology.
Lung cancer is the leading cause of cancer death worldwide, with an estimated 1.8 million deaths in 2020, according to the World Health Organization. Low-dose chest CT is used to screen people at a high risk of lung cancer, such as longtime smokers. It has been shown to significantly reduce lung cancer mortality, primarily by helping to detect cancers at an early stage when they are easier to treat successfully.
While lung cancer typically shows up as pulmonary nodules on CT images, most nodules are benign and do not require further clinical workup. Accurately distinguishing between benign and malignant nodules is therefore crucial to catch cancers early.
For the new study, researchers developed an algorithm for lung nodule assessment using deep learning, an AI application capable of finding certain patterns in imaging data. The researchers trained the algorithm on CT images of more than 16,000 nodules, including 1,249 malignancies, from the National Lung Screening Trial. They validated the algorithm on three large sets of imaging data of nodules from the Danish Lung Cancer Screening Trial.
The deep learning algorithm delivered excellent results, outperforming the established Pan-Canadian Early Detection of Lung Cancer model for lung nodule malignancy risk estimation. It performed comparably to 11 clinicians, including four thoracic radiologists, five radiology residents and two pulmonologists.
“The algorithm may aid radiologists in accurately estimating the malignancy risk of pulmonary nodules,” said the study’s first author, Kiran Vaidhya Venkadesh, a Ph.D. candidate with the Diagnostic Image Analysis Group at Radboud University Medical Center in Nijmegen, the Netherlands. “This may help in optimizing follow-up recommendations for lung cancer screening participants.”
The algorithm potentially brings several additional benefits to the clinic, the researchers said.
“As it does not require manual interpretation of nodule imaging characteristics, the proposed algorithm may reduce the substantial interobserver variability in CT interpretation,” said senior author Colin Jacobs, Ph.D., assistant professor in the Department of Medical Imaging at Radboud University Medical Center in Nijmegen. “This may lead to fewer unnecessary diagnostic interventions, lower radiologists’ workload and reduce costs of lung cancer screening.”
The researchers plan to continue improving the algorithm by incorporating clinical parameters like age, sex and smoking history.
They are also working on a deep learning algorithm that takes multiple CT examinations as input. The current algorithm is highly suitable for analyzing nodules at the initial, or baseline, screening, but for nodules detected at subsequent screenings, growth and appearance in comparison to the previous CT are important.
Dr. Jacobs and colleagues have developed other algorithms to reliably extract imaging features from the chest CT related to chronic obstructive pulmonary diseases and cardiovascular diseases. They will be investigating how to effectively integrate these imaging features into the current algorithm.

What are the most delicate and valuable things you have handled? How would you feel if your daily job involved handling human eggs and any mistakes would affect someone’s life?
Typical egg collection requires a healthy woman to go through weeks of hormone therapy and then undergo an operation to retrieve eggs. These hard-earned and precious eggs are fertilized in vitro, and the best embryos are selected for future transfer.
But not all transfers succeed, which gives rise to the practice of freezing the extra embryos from an IVF cycle for future transfers. This allows those with at-risk fertility, due to age or treatments such as chemotherapy, to delay their transfer.
In the journal Biomicrofluidics, from AIP Publishing, researchers from the National Institute of Genetic Engineering and Biotechnology in Iran and McGill University and the University of British Columbia in Canada introduce a standalone microfluidics system to automate the process of embryo vitrification of replacing water with cryoprotectants.
Water is the enemy of any low-temperature system. Before embryos are frozen, the water inside must be replaced by cryoprotectants. But sudden removal of water kills embryos, so traditionally, embryos are transferred through multiple droplets with increasing concentrations of cryoprotectants. These transfers and washing steps added unnecessary pipetting steps.
“What if embryos simply stayed in the same place, and cryoprotectants were brought to them? Microfluidics systems are really good at controlling flow and concentration,” said Mojtaba Dashtizad, an assistant professor at the National Institute of Genetic Engineering and Biotechnology.
The researchers’ microfluidics setup has one chamber for an embryo to be placed, and three channels to gradually introduce cryoprotectants into it, while existing water is simultaneously emptied through an exit channel. Their single-inlet design of the chip simplifies technicians’ tasks to adding the cryoprotectant solution, placing the embryo, and waiting until the process is completed. The concentration of cryoprotectants is automatically adjusted by the chip.
Unlike the traditional method of cryopreservation, the new approach exposes embryos to a slow and constantly increasing concentration of cryoprotectants.
“Our genetic studies show this reduces molecular damage caused by cryopreservation,” said Dashtizad. “And embryos can be cryopreserved faster and with a lower concentration of cryoprotectants — a huge advantage because of the toxicity of these chemicals.”
This approach enables cryopreservation workflows to be simplified, more reproducible, and less prone to human error.
“Our findings emphasize the importance of moving away from droplet-based loading of cryoprotectants to gradual concentration controls,” said Dashtizad. “These can ultimately reduce damage to embryos during the cryoprocedure, and it moves us one step closer to increasing the efficiency of assisted reproduction and the improved health of future babies.”
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

The COVID-19 pandemic has reinforced the pressing need to mitigate a fast-developing virus as well as antibiotic-resistant bacteria that are growing at alarming rates worldwide.
Photodynamic therapy (PDT), or using light to inactivate viruses, bacteria, and other microbes, has garnered promising results in recent decades for treating respiratory tract infections, such as pneumonia, and some types of cancer.
In Applied Physics Reviews, by AIP Publishing, researchers at Texas A&M University and the University of São Paulo in Brazil review the existing approaches and propose adding antibodies to enhance PDT efficacy. They provide a model to help expedite overall PDT development as a rapid response to emergent viral pandemic threats. The research is based on physical principles to target a wide range of diseases.
“The COVID-19 pandemic calls for extraordinary measures to address current gaps in the therapeutic treatment of infectious diseases, in general, and viral agents, in particular,” author Vladislav Yakovlev said. “We show how photodynamic therapy can be capable of providing an inexpensive alternative strategy in the fight against viral and bacterial infections.”
In PDT, photosensitizers (dyes and other light-reacting compounds) are typically administered intravenously or applied on the skin where treatment is needed. Microbes or cancer cells absorb the photosensitizers. The compounds react to light from a laser to form reactive oxygen species, toxic oxygen molecules that kill the cancer cells or pathogen.
One of the most promising PDT methods highlighted by the researchers is antibody PDT, or aPDT. The method involves attaching photosensitizers to viral antibodies to increase the immune response. The antibody is modified by attaching a small light-absorbing molecule, which upon illumination, can transfer the photon energy to the targeted virus particles, resulting in their destruction while reducing harm to host cells and healthy tissue.
“The aPDT process is characterized by high selectivity, rapid microbial killing, minimal invasiveness, and low occurrence of side effects,” Yakovlev said. “It also ideal for repetitive application without the concern of bacterial resistance.”
The researchers developed a mathematical model to compare PDT to other antiviral treatment by focusing on three parameters critical in modifying the treatment response to determine efficacy: photosensitizer, light, and oxygen.
Molecular oxygen is considered intrinsic to the biological system since it is present at the site of infection. On the other hand, the light dose and the photosensitizer concentration are flexible parameters to achieve efficient results in treatment.
Research protocols, therefore, should consider not only the photosensitizing molecule appropriate to the biological target and adequate wavelength but also the photosensitizer concentration, incubation time, and light dose.
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

A new coronavirus test can get accurate results from a saliva sample in less than 30 minutes, researchers report in the journal Nature Communications. Many of the components of the hand-held device used in this technology can be 3D-printed, and the test can detect as little as one viral particle per 1-microliter drop of fluid.
“We developed a rapid, highly sensitive and accurate assay, and a portable, battery-powered device for COVID-19 testing that can be used anywhere at any time,” said University of Illinois Urbana-Champaign chemical and biomolecular engineering professor Huimin Zhao, who led the research. Though it is still in the prototype stage, the device is estimated to cost less than $78 and the reagents and other materials needed for testing would amount to $6-$7 per test, the researchers found.
Current coronavirus testing technologies are complex, expensive, time-consuming and require bulky equipment and expert analysts, whereas the new device can be operated by anyone with minimal training who is careful when loading samples, Zhao said.
The innovation was made possible by the recent discovery in Zhao’s laboratory of a system for making artificial restriction enzymes that can be programmed to recognize and cleave specific genes in an organism’s genome. In the new device, these enzymes carry DNA guides that tag the viral genes of interest. The enzyme cleaves the genes, which have been tagged with a dye that fluoresces only after the genes are cut. The resulting fluorescence signals that those genes are present — a positive test result.
The new technology, called Scalable and Portable Testing, does away with the complicated process of heating and cooling each sample to get results, as many current testing protocols require. SPOT also can detect multiple genes per sample, making it more accurate than single-gene tests, which can yield incorrect or inconclusive results. Another advantage is that it utilizes saliva, which is easier to collect and less invasive than a nasal swab.
The research team tested SPOT using 104 clinical saliva samples. They found that it accurately identified 28 out of 30 SARS-CoV-2-positive samples and 73 of 74 SARS-CoV-2-negative samples.
“Based on the data reported in the literature, the accuracy of our test is comparable to or better than other SARS-CoV-2 tests,” Zhao said.
The researchers also tested SPOT with samples containing — or lacking — the influenza virus, the new coronavirus and three other human coronaviruses. It accurately identified samples containing the new coronavirus, whether or not other viruses were present in the sample.
“We are interested in exploring this technology for detection of other diseases as well,” Zhao said. “One key advantage to this technology is its multiplexing capability, so in principle, we can detect many viruses simultaneously using the same device.”
The SPOT system also may be useful for detecting genetic markers of certain types of cancer in saliva, he said.
Zhao also is a U. of I. professor of bioengineering, of chemistry, and of biomedical and translational sciences in the Carle Illinois College of Medicine. He is a faculty member in the Carl R. Woese Institute for Genomic Biology, which, together with the Steven L. Miller Chair Endowment, supports this research.
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Materials provided by University of Illinois at Urbana-Champaign. Original written by Diana Yates. Note: Content may be edited for style and length.

Eating a Western diet impairs the immune system in the gut in ways that could increase risk of infection and inflammatory bowel disease, according to a study from researchers at Washington University School of Medicine in St. Louis and Cleveland Clinic.
The study, in mice and people, showed that a diet high in sugar and fat causes damage to Paneth cells, immune cells in the gut that help keep inflammation in check. When Paneth cells aren’t functioning properly, the gut immune system is excessively prone to inflammation, putting people at risk of inflammatory bowel disease and undermining effective control of disease-causing microbes. The findings, published May 18 in Cell Host & Microbe, open up new approaches to regulating gut immunity by restoring normal Paneth cell function.
“Inflammatory bowel disease has historically been a problem primarily in Western countries such as the U.S., but it’s becoming more common globally as more and more people adopt Western lifestyles,” said lead author Ta-Chiang Liu, MD, PhD, an associate professor of pathology & immunology at Washington University. “Our research showed that long-term consumption of a Western-style diet high in fat and sugar impairs the function of immune cells in the gut in ways that could promote inflammatory bowel disease or increase the risk of intestinal infections.”
Paneth cell impairment is a key feature of inflammatory bowel disease. For example, people with Crohn’s disease, a kind of inflammatory bowel disease characterized by abdominal pain, diarrhea, anemia and fatigue, often have Paneth cells that have stopped working.
Liu and senior author Thaddeus Stappenbeck, MD, PhD, chair of the Department of Inflammation and Immunity at Cleveland Clinic, set out to find the cause of Paneth cell dysfunction in people. They analyzed a database containing demographic and clinical data on 400 people, including an assessment of each person’s Paneth cells. The researchers found that high body mass index (BMI) was associated with Paneth cells that looked abnormal and unhealthy under a microscope. The higher a person’s BMI, the worse his or her Paneth cells looked. The association held for healthy adults and people with Crohn’s disease.
To better understand this connection, the researchers studied two strains of mice that are genetically predisposed to obesity. Such mice chronically overeat because they carry mutations that prevent them from feeling full even when fed a regular diet. To the researchers’ surprise, the obese mice had Paneth cells that looked normal.
In people, obesity is frequently the result of eating a diet rich in fat and sugar. So the scientists fed normal mice a diet in which 40% of the calories came from fat or sugar, similar to the typical Western diet. After two months on this chow, the mice had become obese and their Paneth cells looked decidedly abnormal.
“Obesity wasn’t the problem per se,” Liu said. “Eating too much of a healthy diet didn’t affect the Paneth cells. It was the high-fat, high-sugar diet that was the problem.”
The Paneth cells returned to normal when the mice were put back on a healthy mouse diet for four weeks. Whether people who habitually eat a Western diet can improve their gut immunity by changing their diet remains to be seen, Liu said.
“This was a short-term experiment, just eight weeks,” Liu said. “In people, obesity doesn’t occur overnight or even in eight weeks. People have a suboptimal lifestyle for 20, 30 years before they become obese. It’s possible that if you have Western diet for so long, you cross a point of no return and your Paneth cells don’t recover even if you change your diet. We’d need to do more research before we can say whether this process is reversible in people.”
Further experiments showed that a molecule known as deoxycholic acid, a secondary bile acid formed as a byproduct of the metabolism of gut bacteria, forms the link between a Western diet and Paneth cell dysfunction. The bile acid increases the activity of two immune molecules — farnesoid X receptor and type 1 interferon — that inhibit Paneth cell function.
Liu and colleagues now are investigating whether fat or sugar plays the primary role in impairing Paneth cells. They also have begun studying ways to restore normal Paneth cell function and improve gut immunity by targeting the bile acid or the two immune molecules.

Vaccines are turning the tide of the pandemic, but the risk of infection is still present in some situations. If you want to visit a friend, get on a plane, or go see a movie, there is no highly accurate, instant test that can tell you right then and there whether or not you have a SARS-CoV-2 infection. But new research from Lawrence Berkeley National Laboratory (Berkeley Lab) could help get reliable instant tests on the market.
A study led by Michal Hammel and Curtis D. Hodge suggests that a highly sensitive lateral flow assay — the same type of device used in home pregnancy tests — could be developed using pairs of rigid antibodies that bind to the SARS-CoV-2 nucleocapsid protein. Such a test would only require a small drop of mucus or saliva, could give results in 15 minutes, and could detect a COVID-19 infection one day before the onset of symptoms. Their work was published in the journal mABs.
The current gold standard tests for COVID-19 use a form of polymerase chain reaction (PCR) to identify the presence of SARS-CoV-2 nucleic acid (RNA) rather than a viral protein. They are quite accurate, with false negative rates ranging less then 5% (depending primarily on the sampling site, sample type, and stage of infection). However, PCR tests must be sent away for analysis at an accredited lab.
Rapid antigen tests use antibodies to detect specific parts of the viral particle itself. Current antigen tests have a very low rate of false positives, but are plagued by high false negative rates, and therefore can’t replace PCR tests for definitive COVID-19 diagnosis. If a more accurate antigen test was brought to market, it could serve as a helpful initial screening tool similar to how home pregnancy tests work. In the case of a positive result, the user would need to begin appropriate precautionary measures (isolation and other transmission-prevention behaviors) and then have the diagnosis confirmed by an official test at a health clinic.
“As we move toward gaining normalcy and reopening economies worldwide, there is continued demand for rapid, low-cost tests that can be self-administered without the need for a trained professional,” said Hammel, a biophysicist in Berkeley Lab’s Biosciences Area. “Currently used COVID-19 PCR tests are expensive, at about $100 per test, and on average, U.S. labs are performing one million tests per day. An accurate rapid antigen test could cost $1 each and eliminate the wait time.”
Hammel, Hodge, and their colleagues used small angle X-ray scattering (SAXS) performed at Berkeley Lab’s Advanced Light Source (ALS) to examine about 20 antibody-antigen interactions. Their data showed that a particular pair of monoclonal antibodies bound to the nucleocapsid protein very strongly and stably, in part due to the antibodies’ rigidity. All antibodies vary in their degree of rigidity based on the amino acid sequence of their “arms,” which are the part of the Y-shaped molecules that bind to antigens. “The combination of the two rigid antibodies was also observed to increase networking — a process in which multiple antibodies bound to the same antigen at different sites form larger clumps or ‘networks,'” explained Hodge, a postdoctoral researcher and first author on the study.
Antibody networking and high binding stability are known to improve the sensitivity of lateral flow assays, and researchers have long speculated that antibody flexibility plays a role in both properties. But studying the physical dynamics of antibody-antigen pairs to find the most effective antibodies is very difficult with traditional imaging techniques, which require the molecules to be stabilized or crystallized. The SAXS technique developed by Hammel and his colleagues allows scientists to examine antibodies and antigens in their natural state, i.e. when moving freely in a liquid.
“We showed that we can rapidly identify new antibody-antigen pairs that result in a more sensitive detection assay,” said Hammel. “This technique could be applied to hundreds of antibodies in a short amount of time to identify the most suitable antibodies to achieve as-of-yet unattained sensitivity of antibody-based diagnostics, which are key for early diagnosis of SARS-CoV-2 as well as other pathogens.”
The team is now investigating methods of improving test sensitivity even further.
This work was funded through the National Virtual Biotechnology Laboratory (NVBL), a consortium of DOE National laboratories with core capabilities relevant to the threats posed by COVID-19, and funded under the Coronavirus Aid, Relief, and Economic Security (CARES) Act. The ALS is an Office of Science User Facility.
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Materials provided by DOE/Lawrence Berkeley National Laboratory. Original written by Aliyah Kovner. Note: Content may be edited for style and length.

An international team of scientists from the Menzies Health Institute Queensland (MHIQ) at Griffith University and from City of Hope, a research and treatment center for cancer, diabetes and other life-threatening diseases in the U.S., have developed an experimental direct-acting antiviral therapy to treat COVID-19.
Traditional antivirals reduce symptoms and help people recover earlier. Examples include Tamiflu®, zanamivir and remdesivir.
This next-generation antiviral approach used gene-silencing RNA technology called siRNA (small-interfering RNA) to attack the virus’ genome directly, which stops the virus from replicating, as well as lipid nanoparticles designed at Griffith University and City of Hope to deliver the siRNA to the lungs, the critical site of infection.
“Treatment with virus-specific siRNA reduces viral load by 99.9%. These stealth nanoparticles can be delivered to a wide range of lung cells and silence viral genes,” said co-lead researcher Nigel McMillan, Ph.D., professor and director of the Infectious Diseases & Immunology Program at MHIQ.
“Treatment with the therapy in SARS-Cov-2 infected mice improved survival and loss of disease. Remarkably, in treated survivors, no virus could be detected in the lungs,” McMillan said.
Kevin Morris, Ph.D., professor and associate director of the Center for Gene Therapy at City of Hope and co-lead researcher from both City of Hope and Griffith University said, “This treatment is designed to work on all betacoronaviruses such as the original SARS virus (SARS-CoV-1) as well as SARS-CoV-2 and any new variants that may arise in the future because it targets ultra-conserved regions in the virus’ genome.”
McMillan added, “We have also shown that these nanoparticles are stable at 4°C for 12 months and at room temperature for greater than one month, meaning this agent could be used in low-resource settings to treat infected patients.”
The results suggest that siRNA-nanoparticle formulations can be developed as a therapy to treat COVID-19 patients, as well as used for future coronavirus infections by targeting the virus’ genome directly.
“These nanoparticles are scalable and relatively cost-effective to produce in bulk,” Professor Morris said.
“This work was funded as an urgent call by Medical Research Futures Fund and is the type of RNA medicine that can be manufactured locally in Australia,” McMillan said.
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Materials provided by City of Hope. Note: Content may be edited for style and length.

A study using a mouse model of eccentric contraction (*1) has revealed that icing injured muscles delays muscle regeneration. The discovery was made by a research group including Associate Professor ARAKAWA Takamitsu and then PhD. Student KAWASHIMA Masato from Kobe University’s Graduate School of Health Sciences, and Chiba Institute of Technology’s Associate Professor KAWANISHI Noriaki et al. In addition, the researchers illuminated that this phenomenon may be related to pro-inflammatory macrophages’ (*2, 3, 4) ability to infiltrate damaged cells. This research raises questions as to whether or not severe muscle injuries (such as torn muscles) should be iced.
These research results were published online as one of the Journal of Applied Physiology’s Articles in Press on March 25, 2021.
Main points The research results revealed that applying an ice pack to a severe muscle injury resulting from eccentric contraction may prolong the time it takes to heal. The cause of this phenomenon is that icing delays the arrival of pro-inflammatory macrophages, which are responsible for the phagocytosis (*5), or removal, of damaged tissue. Furthermore, this makes difficult for the macrophages to sufficiently infiltrate the damaged muscle cells.Research Background
Skeletal muscle injuries encompass a range of damage to muscles; from a microcellular level to a severe level. These injuries include not only those that happen during sports or schools’ physical education lessons but also external injuries that occur as a result of accidents and disasters.
‘RICE treatment’ is a common approach for skeletal muscle injuries, regardless of the extent of the injury. This acronym stands for Rest, Ice, Compression and Elevation and is often used in physical education, sports and even medicine. Ice is commonly applied regardless of the type of muscle injury, yet little is known about the long-term effects of icing.

The mutant SARS-CoV-2 viruses B.1.1.7 and B.1.351 are classified as “variants of concern,” because they are more easily transmitted than the wild type virus or because our immune system does not recognise them as easily. A research team from Bochum, Jena, Nuremberg and Duisburg-Essen studied how the so-called British and South African variants react to disinfection and cleaning and how long they remain infectious on different surfaces. The researchers found that the variants have a similar surface stability as the wild type virus under laboratory conditions, but can be effectively eliminated by disinfection and thorough hand washing, heat or alcohol treatment. They report their results in the Journal of Infectious Diseases from 16 May 2021.
For this study, the team from the Department for Molecular and Medical Virology and the Chair of Materials Discovery and Interfaces at Ruhr-Universität Bochum (RUB) cooperated with the European Virus Bioinformatics Center Jena, the University Hospital Duisburg-Essen and Paracelsus Medical University Nuremberg.
The fact that viruses change genetically over time is well known. Variants of concern are those that give the virus an advantage, for example by allowing it to replicate faster, become more infectious or enable it to evade the immune response. The British and South African variants have accumulated several mutations which result in an increased transmission and, in some cases, lead to more severe courses of disease. “Therefore, the question arose whether they also differ from the original variant in terms of their sensitivity to hygiene measures,” explains Toni Meister from Ruhr-Universität Bochum.
Heat, soap, alcohol
For this reason, the team analysed how long the variants remain infectious on surfaces made of steel, silver, copper and on face masks and how they can be rendered harmless by means of soap, heat or alcohol.
It turned out that both variants, as well as the wild type virus, could be inactivated when treated with at least 30 percent alcohol for at least 30 seconds. “Common disinfectants are therefore effective against all these variants,” says Stephanie Pfänder from RUB. Thorough hand washing with soap could also lower the risk of infection. Heat also works against the virus: after 30 minutes at 56 degrees Celsius, all variants were rendered harmless.
To find out whether the stability of the different mutant variants on surfaces differs from each other, they analyzed the amount of infectious virus particles on surfaces made of steel, copper, silver and on surgical and FFP2 masks over 48 hours. “The surface stability did not differ between the virus variants,” points out Eike Steinmann from the Department for Molecular and Medical Virology at RUB. “As described several times before, copper in particular has a very strong antiviral effect.” In conclusion, the team did not detect any differences between the different mutants in terms of their sensitivity to different hygiene measures.
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Materials provided by Ruhr-University Bochum. Original written by Meike Drießen; translated by Donata Zuber. Note: Content may be edited for style and length.