Categories : COVID T-cellsTags :

Severe COVID May Lead to Stronger Immunity

On By ModernMedia

Researchers from La Jolla Institute for Immunology (LJI), The University of Liverpool and the University of Southampton have discovered that the degree of COVID severity appears to be linked to how long-lasting and strong the subsequent immunity is. 

“The data from this study suggest people with severe COVID-19 cases may have stronger long-term immunity,” said study co-leader LJI Professor Pandurangan Vijayanand, MD, PhD.

The research examines T-cells from COVID infections in unprecedently high detail.

“This study highlights the enormous variability in how human beings react to a viral challenge,” added co-leader Christian Ottensmeier, MD, PhD, FRCP, a professor at the University of Liverpool and adjunct professor at LJI.

Vijayanand and Ottensmeier have been studying how antibodies and the different subsets of T-cells control COVID disease severity. In this study, they examined CD8+ T-cells, which are the T-cells responsible for destroying virus-infected cells, and “memory” CD8+ T-cells are also important for guarding the body against reinfections of the same virus. These memory T-cells are poised to rapidly proliferate and engage their cell-destroying functions on subsequent antigen encounters. They can reside in peripheral organs and their memory can also be shaped by infection history.

Utilising a new technique called single-cell transcriptomics analysis, they were able to study expressions of individual genes of 80 000 CD8+ T-cells drawn from 39 COVID patients and from 10 non-exposed donors, whose blood samples had been taken before the pandemic. Of the COVID patients, 17 cases were mild and non-hospitalised, 13 were hospitalised and 9 had required ICU care.

Surprisingly, the researchers found that the strongest CD8+ T-cell responses were from those with the more severe form of the disease, and not the milder cases.”There is an inverse link between how poorly T cells work and how bad the infection is,” observed Ottensmeier. “I think that was quite unexpected.” A stronger response would be expected from CD8+ T-cells in mild cases due to having the resources of a better functioning immune system. However, the mild group of CD8+ T-cells showed signs of “exhaustion”, which happens when the immune system overloads the T-cells, causing them to lose effectiveness.

The researchers believe that it will be beneficial to study whether this phenomenon may hinder the ability to build long-term immunity.

“People who have severe disease are likely to end up with a good number of memory cells,” said Vijayanand. “People with milder disease have memory cells, but they seem exhausted and dysfunctional—so they might not be effective for long enough.

“What the researchers would like to look at next is to look at T-cells from lung tissue as opposed to blood samples, because that is where the infection hits hardest.

“This study is very much a first step in understanding the spectrum of immune responses against infectious agents,” said Ottensmeier. The researchers will also look at T-cells in cancer patients who are also infected with COVID.

Source: Medical Xpress

Journal information: Anthony Kusnadi et al, Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells, Science Immunology  21 Jan 2021: Vol. 6, Issue 55, eabe4782 DOI: 10.1126/sciimmunol.abe4782

Categories : New Compounds and TreatmentsTags :

Paralysed Mice Walk Again with ‘Designer’ Cytokines

On By ModernMedia

Scientists have sought a means to regenerate spinal cord injuries which leaves patients paraplegic or quadriplegic – and now a breakthrough by researchers at Ruhr-University Bochum, Germany, may see that dream realised.

By the time humans reach adulthood, after an injury they can no longer regenerate the axons which transfer nerve impulses from brain to muscles. In 2013, the researchers discovered that a cytokine called interleukin-6 (IL-6) promoted the regeneration of optic axon fibres in vitro. IL-6 was known to be involved in nerve regeneration as well as in neuropathic pain from peripheral nerve injuries. As promising as this experiment was, delivery of the cytokine to the injury location deep in the body was an obstacles, as was the fact that it had a fairly weak effect on stimulating nerve tissue regrowth.

The team subsequently developed hyper-IL-6, an artificial variant of IL-6 that was far more potent than its natural counterpart. However, the “designer” cytokine still could not be delivered to the injured tissue where it was needed. To get around this, the researchers turned to a somewhat novel delivery method: gene therapy. A few motor neurons in the brain’s sensorimotor cortex are altered via engineered viruses to produce hyper-IL-6, which is then distributed along the axon’s length to the injury site.

“Thus, gene therapy treatment of only a few nerve cells stimulated the axonal regeneration of various nerve cells in the brain and several motor tracts in the spinal cord simultaneously,” explained senior author Dr Dietmar Fischer.

After a single injection of the engineered virus and its hyper-IL-6 payload, mice with severed spinal cords were able to walk again after two to three weeks.

“This came as a great surprise to us at the beginning, as it had never been shown to be possible before after full paraplegia,” said Dr. Fischer.
Following the success of these experiments, Dr. Fischer’s team is looking at combining the engineered cytokine treatment to other promising applications, such as tissue grafts. Additionally, they are investigating whether the hyper-IL-6 treatment can regenerate spinal cord damage that occurred weeks beforehand.

“This aspect would be particularly relevant for application in humans. We are now breaking new scientific ground. These further experiments will show, among other things, whether it will be possible to transfer these new approaches to humans in the future.”

However, adapting this designer cytokine treatment to be one that is safe for humans will take several years.

Source: Medical News Today

Categories : COVIDTags :

Biden’s Promise to “Manage the Hell” out of COVID

On By ModernMedia

Almost immediately upon assuming office, the newly sworn-in President Joe Biden started to deliver on his promise to tackle the COVID pandemic raging in the United States.

On Wednesday, shortly after being sworn in, he wrote to both the United Nations Secretary General and the WHO Director General to notify them of the United States’ return to the WHO – a move no doubt welcomed around the world. He also began to sign a raft of orders related to the COVID pandemic.

Following up on his promise to “manage the hell” out of the COVID pandemic, President Biden signed a directive which “seeks to support the international health and humanitarian response to the COVID-19 pandemic and its secondary impacts, global health security and diplomacy, and better biopreparedness and resilience for emerging and future biological threats.”

His actions and executive orders include:– Increased equipment procurement. Using the Defense Production Act (DPA) to accelerate manufacturing and meet shortfalls in COVID-related equipment and supplies.
– Increased COVID testing. Another order establishes a testing board to help expand the supply of tests and testing equipment, as well as supporting the public healthcare force.
– Increasing studies on COVID-19 treatments. More studies requested on COVID, as well as on COVID in diverse populations. Also requests more healthcare workers.
– Speeding up vaccinations. Federal Emergency Management Agency (FEMA) is directed to begin deploying vaccination centres, aiming toward a goal of 100 in the next month.
– Reopening schools and businesses. The Departments of Education and Health and Human Services (HHS) are directed to provide guidance on safe reopening and operating for education institutions and child care providers.
– Improving protections for workers. Clear guidance for employers to keep employees safe from COVID exposure.
– Increasing travel safety. Masks are to be worn in federal buildings, and mask requirements are extended to interstate travel, including on planes, trains, and buses. People flying into the US from another country will need to test negative for COVID prior to departure and quarantine upon arrival.

President Biden’s plan and the full texts of the executive orders were detailed in a 200 page document which was made available on Thursday.

At a White House signing ceremony, he affirmed his commitment to “following the science” on COVID, saying: “We will make sure that scientists and public health experts will speak directly to you — not the president, but real, genuine experts and scientists.” He added that they will work free of political interference.

He also warned Americans of a “dark winter” ahead, and the nation was in a national emergency and that “we should treat it like one.”

Source: MedPage Today

Categories : New Compounds and TreatmentsTags :

Antifungal Compound Discovered in Ant Farms

On By ModernMedia

Researchers in Brazil have discovered an antifungal compound by bacteria living in ant farms, which may have medical applications.

In the fungal farms where attine ants tend as their food source, Pseudonocardia and Streptomyces bacteria produce metabolites which shield the crop against pathogens. Curiously, these metabolites vary across geographic locations.

Attine ants are a type of ant which grow and harvest fungus for food, and are only found in the Western Hemisphere. They first evolved from a common Amazonian ancestor some 50 million years ago, giving rise to some 200 species of ants spread across South and Central America, which share common farming practices. The bacteria at these farms have a symbiotic relationship where they defend against fungi such as Escovopsis in exchange for food.

These metabolites vary considerably, suggesting a fragmented history. Searching a number of ant nests spread across a large geographical area, the researchers discovered that two thirds of the Pseudonocardia strains were producing the same metabolite. They named this newly discovered metabolite attinimicin.The study was the first one where a common, specialised metabolite produced by ant-associated bacteria was found across geographic locations.

Attinimicin inhibited fungal parasites while not harming the fungal crop, but only in the presence of iron. It proved as effective in treating Candida albicans infections in mice as a clinically used azole-containing antifungal. This means that the metabolite could have clinical applications. Attinimicin was shown to have a similar structure to two other metabolites produced by Streptomyces, suggesting the responsible genes have a common evolutionary origin.

Source: News-Medical.Net

Journal information: Fukuda, T.T.H., et al. (2021) Specialized Metabolites Reveal Evolutionary History and Geographic Dispersion of a Multilateral Symbiosis. ACS Central Science. doi.org/10.1021/acscentsci.0c00978.

Categories : AntibioticsTags :

Prevalence of Antibiotic Resistance is Underestimated

On By ModernMedia

Antibiotic resistance to pathogenic bacteria in humans has spread farther than expected, as it has been discovered that bacteria can swap DNA far more readily than thought possible.

A growing threat, antibiotic resistance has emerged faster than thought possible. Some 33 000 deaths have occurred to antibiotic resistant infections in Europe alone, and finding new antibiotics or even alternatives are a top research priority. Totally different strains of bacteria can swap genetic information through the use of containers called plasmids. Plasmids are small containers of DNA which are kept outside of their chromosomes. When two bacteria come into contact, they can copy plasmids to one another in a process called conjugation (also known as “bacterial sex“). This is the most important means by which bacteria spread antibiotic resistance.

“In recent years, we’ve seen that resistance genes spread to human pathogens to a much greater degree than anyone expected,” said Jan Zrimec, a researcher in systems and synthetic biology at the Chalmers University of Technology. “Many of the genes appear to have originated in a wide array of bacterial species and environments, such as soil, water, and plant bacteria.

“This has been difficult to explain because although conjugation is very common, we’ve thought that there was a distinct limitation for which bacterial species can transfer plasmids to each other. Plasmids belong to different mobility groups or MOB groups, so they can’t transfer between just any bacterial species.”

Among his developments, he has written an algorithm that can sift through substantial amounts of plasmid DNA to pick out sections of DNA which are necessary for conjugation (known as oriT regions, where the enzyme relaxase can bind to and snip out DNA). This algorithm can then sort the plasmids into groups based on their oriT regions. His new method differs from the standard one because it analyses oriT regions by their physiochemical properties instead of searching DNA for the enzyme sequence for relaxase, or the point where it can bind to. This method is less time-consuming and resource intensive than the standard one.

Previously, it was thought that a plasmid had to have both the relaxase enzyme and the oriT sequence to bind to, but a bacterial cell can have an oriT region for conjugation to occur. With his new algorithm, he has been able to explore the DNA of 4600 plasmids from different bacteria found in nature.
– There may be eight times as many oriT regions than those discovered with standard methods.
– There may be twice as many mobile plasmids as previously known.
– There also may be twice as many bacterial species with mobile plasmids as previously known.
– More than half the plasmids have an oriT group matching to an enzyme for conjugation from a plasmid that already been classified in a different MOB group. This means that they could be transferred from a different plasmid in the same cell.

The last finding suggests that there may be far greater interchange between bacteria than had been previously been believed.

“This has been a major limitation of the research field up to now,” Zrimec said. “I hope that the methods will be able to benefit large parts of the research into antibiotic resistance, which is an extremely interdisciplinary and fragmented area. The methods can be used for studies aiming to develop more effective limitations to antibiotic use, instructions for how antibiotics are to be used, and new types of substances that can prevent the spread of resistance genes at the molecular level.”

Source: News-Medical.Net

Journal information: Zrimec, J. (2021) Multiple plasmid origin‐of‐transfer regions might aid the spread of antimicrobial resistance to human pathogens. MicrobiologyOpen.doi.org/10.1002/mbo3.1129.

Categories : Implants and ProsthesesTags :

New Type of Corneal Implant Fuses into the Eye

On By ModernMedia

A new type of artificial cornea has been successfully implanted into an elderly patient, who demonstrated recovered sight the day after his surgery.

When the cornea is damaged by disease or injury, blindness can result, necessitating a cornea transplant. Artificial corneas are a much sought-after technology, as the normal treatment for a damaged cornea is to seek a transplanted replacement. However, for every 70 corneas sought, there is only a single donor cornea. CorNeat Vision is set to offer the first commercially available synthetic cornea implant, the KPro.

The new cornea has a clear centre section, surrounded by a white skirt consisting of electrospun nanofibres. Electrospun nanofibres have already found application in many medical applications, such as a new kind of translucent burn dressing. This skirt’s nanofibre material allows fibroblasts and collagen to infiltrate its structure, allowing full integration within a few weeks of surgery. This biomimetic technology results in faster healing times, the ability to use fully synthetic implants and is fully scalable as it does not rely on any harvested tissue.

The implantation procedure involves removing the epithelium covering the cornea, marking the location of where the artificial cornea implant should go, removing the cornea and then suturing its replacement into position.

Only a day after his surgery, the first recipient of this new artificial cornea was able to make out the faces of his relatives and read numbers off of a chart.

Source: Medical Xpress

Categories : COVID Expert OpinionTags :

UCT Expert Talks COVID and Warns of Third Wave

On By ModernMedia

If South Africa does not pursue a rapid vaccination programme to achieve herd immunity, it may face a third wave as a consequence, warned a leading local expert.

Professor Marc Mendelson of UCT’s Division of Infectious Diseases and HIV Medicine at Groote Schuur Hospital made these statements while speaking during a virtual Summer School lecture on Saturday, titled “COVID-19 Insights and Lessons”.

“Without rapid vaccination of at least two thirds of the population, we [South Africa] are not going to get to population immunity, and without that, we will see another wave,” Mendelson warned.

However, he emphasised that much had been accomplished in the battle against COVID. “It is associated with a scientific endeavour that we have never seen before. We’re definitely better off a year down the line, but there are a huge number of things that we need to answer. As a country we still face deep problems with severe issues around vaccine strategy, and we haven’t even talked about vaccine denial,” he said.

Criticism has been directed at the South African government because of its failure to start a vaccination programme, despite its huge case load and status as Africa’s most wealthy nation. A leaked phone call from a Pfizer executive has only added to this, as it was revealed that for months SA health officials had not been responding to requests for vaccine discussions.

Regarding COVID transmission, he said that the virus resided in the upper respiratory tract as well as the lungs, and that it could be expelled in aerosol droplets. The clinical and epidemiological evidence suggested that larger, heavier droplets carried the virus.

“The household infection rates were high. A very large number of cases, the vast majority [in fact], were within families in close proximity [to one another]. This, epidemiologically, suggests that large droplets play a role in transmission.

“If you want to reduce transmission from large droplets, then you need to increase the distance you are from someone. Also, because droplets drop onto surfaces … you will need to clean surfaces and wash your hands well. This is the science behind the use of masks, handwashing, social distancing and ventilation.”

However, he added that a number of studies had found the virus in remote corners of hospitals at a distance from patients, suggesting that it had been carried there by smaller, aerosolised particles.

“If you want to reduce aerosols, one way of doing that is to improve ventilation. The more the air is changed, the [quicker] it will dilute small droplets,” he said.

Source: University of Cape Town

Categories : Uncategorized

South African 510Y.V2 COVID Strain Resistant to Previous Antibodies

On By ModernMedia

Results from a National Institute of Communicable Diseases (NICD) study shows that immunity gained against the initial strains of SARS-CoV-2 is blunted against the new 501Y.V2 strain that originated in South Africa.

The new variants which are more transmissible have mutations to their spike proteins that give the coronavirus its distinctive shape—and to which immune antibodies bind. Scientists have been concerned that the new strains may also escape vaccine containment, especially the E484K mutation, which has been observed in new strains found in Brazil and South Africa.

In the study, which is awaiting peer review, researchers took plasma from patients who had recovered from the original COVIDs, and tested those samples against the 501Y.V2 virus variant to measure antibody reaction. The virus was more resistant to these antibodies, which had been built up from previous infections. “Here we show that the 501Y.V2 lineage, which contains nine spike mutations and rapidly emerged in South Africa during the second half of 2020, is largely resistant to neutralising antibodies elicited by infection with previously circulating lineages,” said the researchers.

“This suggests that, despite the many people who have already been infected with SARS-CoV-2 globally and are presumed to have accumulated some level of immunity, new variants such as 501Y.V2 pose a significant re-infection risk.”

The researchers noted that these findings may have implications for those treated with convalescent plasma (a donor programme for which  is run by the South African National Blood Service). Additionally, there were “implications” for those vaccines that were developed based around an immune response to the virus’ spike proteins.

Vaccines may therefore have to be adjusted to account for the new spike mutation in order to retain effectiveness against variants possessing that mutation. The developers of the Oxford/AstraZeneca vaccine are already preparing to proactively adjust their vaccines to account for the new strains emerging around the world.

Commenting to the Science Media Centre, Lames Naismith, Director of the Rosalind Franklin Institute said that it was “not good news but it’s not unexpected.

“He said that real-world immune responses are more complicated than those of the blood plasma neutralising antibodies. “The vaccines do stimulate very strong responses, immunity is a sliding scale, it’s not an on/off switch,” he explained.

In another study posted online, it was reported that antibodies from recovered patients did mostly protect against B.1.1.7, the variant that originated in the UK.

“Our results suggest that the majority of vaccine responses should be effective against the B.1.1.7 variant,” concluded researchers from one the UK/Netherlands studies.

A separate study showed that the Pfizer/BioNTech vaccine also appeared to confer protection against that variant as well, with the authors concluding that it was “unlikely” that the B.1.1.7 variant could escape vaccine protection.

Source: Medical Xpress

Categories : Diet and NutritionTags :

High-carb and High-fat Diets Compared

On By ModernMedia

Plant-based diets high in carbohydrates and meat-centred diets high in fats have become increasingly popular in recent years, and a new small, tightly controlled study has investigated their effects.

A myriad of health benefits ascribed to plant-based diets, while high-fat, low-carb diets have been proposed as a way to counteract overweight and diabetes risk. But there has been little understanding on how exactly the two diets compare, given that they restrict either fats or carbohydrates.

The answers to these questions were sought by a team at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).”High-fat foods have been thought to result in excess calorie intake because they have many calories per bite. Alternatively, high-carb foods can cause large swings in blood glucose and insulin that may increase hunger and lead to overeating,” said the study’s lead author, NIDDK Senior Investigator Kevin Hall, PhD. “Our study was designed to determine whether high-carb or high-fat diets result in greater calorie intake.”

The study took 11 male and 9 female non-diabetic participants and housed them in a facility for four weeks. For two weeks, they were served either a low-fat, high-carb, plant-based diet or a low-carb, high-fat meat-based diet. They were then changed to the other diet for the next two weeks. The food was minimally processed, contained equivalent amounts of non-starchy vegetables and participants were allowed snacks and to eat as much as they wanted.

The participants ate 550 to 700 fewer calories per day than when they ate the low-carb diet. Despite this difference, participants reported no hunger, and the same level of fullness and satisfaction with both diets. The participants lost weight on both diets, but more so on the low-fat diet.

“Despite eating food with an abundance of high glycemic carbohydrates that resulted in pronounced swings in blood glucose and insulin, people eating the plant-based, low-fat diet showed a significant reduction in calorie intake and loss of body fat, which challenges the idea that high-carb diets per se lead people to overeat. On the other hand, the animal-based, low-carb diet did not result in weight gain despite being high in fat,” Hall said.

The results add to a growing body of evidence that shows that diet is much more complex than just total calories. Hall’s previous research found that participants who ate highly processed food let to overeating and weight gain compared to a minimally processed carbs and fat-matched diet.

In this case, however, there were benefits observed in both diets.

“Interestingly, our findings suggest benefits to both diets, at least in the short-term. While the low-fat, plant-based diet helps curb appetite, the animal-based, low-carb diet resulted in lower and more steady insulin and glucose levels,” Hall commented. “We don’t yet know if these differences would be sustained over the long term.”

However, weight loss was not a goal of the study, and that may have influenced participants’ eating behaviours and the outcome of the study. The inpatient setting of the study also controlled what foods were available, unlike daily life where a variety of options, costs, preparation and availability concerns influence food choices. 

Source: Medical Xpress

Categories : COVIDTags :

WHO Warns of ‘Catastrophic Failure’ over COVID Vaccination

On By ModernMedia

The World Health Organization head, Dr Tedros Adhanom Ghebreyesus, has warned that the world faces a “catastrophic moral failure” because of unequal access to COVID vaccines. 

He said that 49 wealthier states had conducted 39 million vaccinations between them, but one poor country had only 25 doses.

To date, the US, China, India, Russia and the UK have all developed vaccines, and mostly prioritised their own populations to receive them – although the German company BioNTech developed theirs in collaboration with Pfizer, and even so, the EU failed to secure vaccines sufficiently in advance. 

Dr Tedros spoke to an executive board session of the WHO, saying: “I need to be blunt: the world is on the brink of a catastrophic moral failure – and the price of this failure will be paid with lives and livelihoods in the world’s poorest countries.”

He warned that a selfish approach to vaccination would lead to hoarding and rising prices.

“Ultimately, these actions will only prolong the pandemic, the restrictions needed to contain it, and human and economic suffering,” he added.

Calling on nations to accelerate their progress, he said: “My challenge to all member states is to ensure that by the time World Health Day arrives on 7 April, Covid-19 vaccines are being administered in every country, as a symbol of hope for overcoming both the pandemic and the inequalities that lie at the root of so many global health challenges.” 

Thus far, 180 countries have signed on to the Covax initiative, which aims to negotiate as a bloc for lower vaccine prices. The initiative aims to distribute vaccines to low- and middle income countries, 92 of which will have their vaccines paid for by the initiative. Dr Tedros said that two billion doses had been secured, with an option of a billion more, with the first doses delivered by February.

UK Health Secretary Matt Hancock said in a reaction to Dr Tedros’ warnings that, “The UK is the world’s biggest supporter, financial supporter, of the global programme to ensure access to vaccines in all countries in the world.”

The UK has contributed £548m ($734m) to the Covax initiative. Canada drew criticism after it was revealed that, due to vaccine hoarding, the 70 poorest countries would only be able to vaccinate 10% of their population, while Canada had secured enough vaccines for five times its population of nearly 38 million. However, these vaccines are “hypothetical” according to Karina Gould, Canada’s minister of international development. Canada is also contributing $380 million to Covax. Furthermore, discussions are reportedly under way for South Africa to secure some of the vaccines allocated to Canada.

Source: BBC News