Publisher Health

Children with weakened immune systems have not shown a higher risk of developing severe COVID-19 infection despite commonly displaying symptoms, a new study suggests.
During a 16-week period which covered the first wave of the pandemic, researchers from Southampton carried out an observational study of nearly 1500 immunocompromised children — defined as requiring annual influenza vaccinations due to underlying conditions or medication. The children, their parents or guardians completed weekly questionnaires to provide information about any symptoms they had experienced, COVID-19 test results and the impact of the pandemic on their daily life.
The results, published in BMJ Open, showed that symptoms of COVID-19 infection were common in many of the children — with over two thirds of participants reporting at least one symptom and one third experiencing three or more symptoms simultaneously. One hundred and ten patients with symptoms undertook viral PCR tests, none of whom tested positive.
Dr Hans de Graaf from the University of Southampton who led the research said, “Whilst we cannot be certain of the prevalence of COVID-19 amongst the children who took part, because testing was only done when patients were admitted and these children were told to adhere to strict shielding measures, we can assume that any infections would have been mild cases since none of these high risk patients required hospital admissions.”
More than half of the patients or parents reported high levels of anxiety at the start of the study and despite the absence of severe symptoms, these scores remained consistently high throughout the study period.
The researchers believe that these results show that widespread symptom screening for early detection of COVID-19 in not going to be useful in these cases as the children may have frequent upper respiratory tract symptoms likely to be unrelated to COVID-19.
Dr de Graaf continued, “This study was the first to observe the impact of the pandemic on children with compromised immune systems. During the first wave of the pandemic, many may have been shielding so our results suggest that either the shielding measures were effective or that immunocompromised children are less affected by COVID-19 than adults, just like healthy children.”
The report also concludes that the continuous high level of anxiety among participants highlights the need to clearly define and communicate the risk of COVID-19 in children and young people, particularly as lockdown restrictions ease.
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Substantial cuts in global greenhouse gas emissions could be achieved by raising water levels in agricultural peatlands, according to a new study in the journal Nature.
Peatlands occupy just three per cent of the world’s land surface area but store a similar amount of carbon to all terrestrial vegetation, as well as supporting unique biodiversity.
In their natural state, they can mitigate climate change by continuously removing CO2 from the atmosphere and storing it securely under waterlogged conditions for thousands of years.
But many peatland areas have been substantially modified by human activity, including drainage for agriculture and forest plantations. This results in the release, from drained peatlands, of the equivalent of around 1.5 billion tonnes of carbon dioxide (CO2) into the atmosphere each year — which equates to three per cent of all global greenhouse gas (GHG) emissions caused by human activities.
A team of scientists, led by the UK Centre for Ecology and Hydrology (UKCEH), estimated the potential reduction in emissions by restoring all global agricultural peatlands. However, because large populations rely on these areas for their livelihoods, it may not be realistic to expect all agricultural peatlands to be fully rewetted and returned to their natural condition in the near future.
The team therefore also analysed the impact of halving current drainage depths in croplands and grasslands on peat — which cover over 250,000km2 globally — and showed that this could still bring significant benefits for climate change mitigation. The study estimates this could cut emissions by around 500 million tonnes of CO2 a year, which equates to 1 per cent of all global GHG emissions caused by human activities.

Coronavirus researchers led by Professor Rolf Hilgenfeld of the University of Luebeck and PD Dr. Albrecht von Brunn of the Ludwig-Maximilian Universitaet (LMU) in Munich have discovered how SARS viruses enhance the production of viral proteins in infected cells, so that many new copies of the virus can be generated. Notably, coronaviruses other than SARS-CoV and SARS-CoV-2 do not use this mechanism, which may therefore provide a possible explanation for the much higher pathogenicity of the SARS viruses. The findings appear in the EMBO Journal.
Coronaviruses that cause harmless colds in humans were discovered more than 50 years ago. When it emerged in 2002/2003, the SARS coronavirus was the first coronavirus found to cause severe pneumonia in infected people. Comparisons of the RNA genomes of innocuous coronaviruses with those of the SARS coronavirus permitted researchers to identify a region that only occurred in the latter, and was called the “SARS-unique domain” (SUD). Such genomic regions and their protein products might be linked to the extraordinary pathogenicity of SARS coronavirus and its cousin, the COVID-19 virus SARS-CoV-2.
The research groups led by Hilgenfeld and von Brunn showed that the SUD proteins of these two viruses interact with a human protein called Paip-1, which is involved in the first steps of protein synthesis. Together with Paip-1 and other proteins in human cells, SUD apparently binds to the ribosomes, the molecular machines that are responsible for protein synthesis in cells. This would lead to an enhancement of the production of all proteins, both those of the host cell and those of the virus. However, in cells infected with SARS-CoV or SARS-CoV-2, the messenger RNA molecules that code for host proteins are selectively destroyed by a viral protein named Nsp1. As a result of this complicated process, the infected cell predominantly produces viral proteins, so that many new copies of the virus can be created.
Albrecht von Brunn’s research group discovered the interaction between the proteins SUD and Paip-1 several years ago. “Being an experienced coronavirologist, I knew that one has to inspect the special regions of the SARS genome when trying to understand this virus,” he says.
The discovery made by the Munich researchers was of great interest to Hilgenfeld, whose research group had already elucidated the three-dimensional structure of the SUD protein some years previously. The two research groups teamed up. Dr. Jian Lei in Hilgenfeld’s group, meanwhile a group leader at Sichuan University in Chengdu (China), succeeded in crystallizing the complex formed by SUD and Paip-1 and determining its three-dimensional structure by X-ray crystallography. And co-first author Dr. Yue “Lizzy” Ma-Lauer of von Brunn’s group characterized the complex of the two proteins and its function using a variety of cell-biological and biophysical methods.
“Interaction studies of this kind between coronavirus proteins and proteins of the infected human cell will help us understand how the viruses change key functions of the cell to their own benefit,” says Hilgenfeld. The project was supported by the German Federal Ministry of Education and Research (BMBF) and by the German Center for Infection Research (DZIF).
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A new approach to gene editing using the CRISPR/Cas9 system bypasses disease-causing mutations in a gene, enabling treatment of genetic diseases linked to a single gene, such as cystic fibrosis, certain types of sickle cell anemia, and other rare diseases. The method, developed and tested in mice and human tissue cultures by researchers at Penn State, involves inserting a new, fully functional copy of the gene that displaces the mutated gene.
A proof-of-concept for the approach is described in a paper appearing online April 20 in the journal Molecular Therapy.
The CRISPR/Cas9 system has allowed promising new gene therapies that can target and correct disease-causing mutations in a gene. In this process, Cas9 — a bacterial protein — cuts DNA at a specific location, where the genetic sequence can then be edited, trimmed, or a new sequence inserted before the DNA is repaired. However, there are two main limitations to current repair strategies. First, the common repair strategy, called “homology-directed repair,” requires using specific proteins within the cell that are only present during cell division, which means the gene repair process cannot be used in most adult tissues where cell division occurs rarely.
“The second challenge stems from the fact that even when a disease is caused by a single gene, it can result from a variety of different mutations within that gene,” said Douglas Cavener, professor of biology at Penn State and senior author of the paper. “With homology-directed repair, we’d need to design and test the strategy for each and every one of those mutations, which can be expensive and time-intensive. In this study, we designed an approach called Co-opting Regulation Bypass Repair (CRBR), which can be used in both dividing and non-dividing cells and tissues and for a spectrum of mutations within a gene. This approach is especially promising for rare genetic diseases caused by a single gene, where limited time and resources typically preclude design and testing for the many possible disease-causing mutations.”
CRBR takes advantage of the CRISPR/Cas9 system and a cellular repair pathway called “non-homologous end joining” to insert a genetic sequence between a mutated gene’s promoter region — the genetic sequence that controls when and where the gene is functional — and the mutated portion of the gene. The newly inserted sequence contains a condensed version of the normal gene that is used in place of the mutated version. A terminator sequence at the end of the inserted sequence prevents the remaining downstream mutated gene from being used. Because CRBR does not rely on the proteins required by homology-directed repair, it can be used in all types of adult tissues.
“Our approach co-opts the native promoter for a gene,” said Jingjie Hu, a graduate student at Penn State and first author of the paper. “This means that the newly inserted gene will be expressed at the same times and at appropriate levels within the cell as the gene it is replacing. This is an advantage to other types of gene therapies, which rely on an external promoter to drive high levels of expression of the gene that could lead to negative effects if too much is produced or if essential regulation response is missing under certain physiological conditions.”
The research team conducted a series of proof-of-concept experiments to demonstrate the utility of this method. They first focused on the PERK gene, mutations in which can lead to a rare disease called Wolcott-Rallison syndrome. The syndrome results when copies of the gene inherited from both parents have mutations — it is a “recessive” disease — and can cause neonatal diabetes, skeletal problems, growth delay, and other symptoms.

Careful criminals usually clean a scene, wiping away visible blood and fingerprints. However, prints made with trace amounts of blood, invisible to the naked eye, could remain. Dyes can detect these hidden prints, but the dyes don’t work well on certain surfaces. Now, researchers reporting in ACS Applied Materials & Interfaces have developed a fluorescent polymer that binds to blood in a fingerprint — without damaging any DNA also on the surface — to create high-contrast images.
Fingerprints are critical pieces of forensic evidence because their whorls, loops and arches are unique to each person, and these patterns don’t change as people age. When violent crimes are committed, a culprit’s fingerprints inked in blood can be hard to see, especially if they tried to clean the scene. So, scientists usually use dyes to reveal this type of evidence, but some of them require complex techniques to develop the images, and busy backgrounds can complicate the analysis. In addition, some textured surfaces, such as wood, pose challenges for an identification. Fluorescent compounds can enhance the contrast between fingerprints and the surface on which they are deposited. However, to get a good and stable image, these molecules need to form strong bonds with molecules in the blood. So, Li-Juan Fan, Rongliang Ma and colleagues wanted to find a simple way to bind a fluorescent polymer to blood proteins so that they could detect clear fingerprints on many different surfaces.
The researchers modified a yellow-green fluorescent polymer they had previously developed by adding a second amino group, which allowed stable bonds to form between the polymer and blood serum albumin proteins. They dissolved the polymer and absorbed it into a cotton pad, which was placed on top of prints made with chicken blood on various surfaces, such as aluminum foil, multicolored plastic and painted wood. After a few minutes, they peeled off the pad, and then let it air-dry. All of the surfaces showed high contrast between the blood and background under blue-violet light and revealed details, including ridge endings, short ridges, whorls and sweat pores. These intricate patterns were distinguishable when the researchers contaminated the prints with mold and dust, and they lasted for at least 600 days in storage. In another set of experiments, a piece of human DNA remained intact after being mixed with the polymer, suggesting that any genetic material found after processing a print could still be analyzed to further identify a suspect, the researchers say.
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After a particularly vigorous workout or sports injury, many of us rely on ice packs to reduce soreness and swelling in our twanging muscles. But a cautionary new animal study finds that icing alters the molecular environment inside injured muscles in detrimental ways, slowing healing. The study involved mice, not people, but adds to mounting evidence that icing muscles after strenuous exercise is not just ineffective; it could be counterproductive.Check inside the freezers or coolers at most gyms, locker rooms or athletes’ kitchens and you will find ice packs. Nearly as common as water bottles, they are routinely strapped onto aching limbs after grueling exercise or possible injuries. The rationale for the chilling is obvious. Ice numbs the affected area, dulling pain, and keeps swelling and inflammation at bay, which many athletes believe helps their aching muscles heal more rapidly.But, in recent years, exercise scientists have started throwing cold water on the supposed benefits of icing. In a 2011 study, for example, people who iced a torn calf muscle felt just as much leg pain later as those who left their sore leg alone, and they were unable to return to work or other activities any sooner. Similarly, a 2012 scientific review concluded that athletes who iced sore muscles after strenuous exercise — or, for the masochistically minded, immersed themselves in ice baths — regained muscular strength and power more slowly than their unchilled teammates. And a sobering 2015 study of weight training found that men who regularly applied ice packs after workouts developed less muscular strength, size and endurance than those who recovered without ice.But little has been known about how icing really affects sore, damaged muscles at a microscopic level. What happens deep within those tissues when we ice them, and how do any molecular changes there affect and possibly impede the muscles’ recovery?So, for the new study, which was published in March in the Journal of Applied Physiology, researchers at Kobe University in Japan and other institutions, who long had been interested in muscle physiology, gathered 40 young, healthy, male mice. Then, using electrical stimulation of the animals’ lower legs to contract their calf muscles repeatedly, they simulated, in effect, a prolonged, exhausting and ultimately muscle-ripping leg day at the gym.Melody Melamed for The New York TimesRodents’ muscles, like ours, are made up of fibers that stretch and contract with any movement. Overload those fibers during unfamiliar or exceptionally strenuous activities and you damage them. After healing, the affected muscles and their fibers should grow stronger and better able to withstand those same forces the next time you work out.But it was the healing process itself that interested the researchers now, and whether icing would change it. So, they gathered muscle samples from some animals immediately after their simulated exertions and then strapped tiny ice packs onto the legs of about half of the mice, while leaving the rest unchilled. The scientists continued to collect muscle samples from members of both groups of mice every few hours and then days after their pseudo-workout, for the next two weeks.Then they microscopically scrutinized all of the tissues, with a particular focus on what might be going on with inflammatory cells. As most of us know, inflammation is the body’s first response to any infection or injury, with pro-inflammatory immune cells rushing to the afflicted area, where they fight off invading germs or mop up damaged bits of tissue and cellular debris. Anti-inflammatory cells then move in, quieting the inflammatory ruction, and encouraging healthy new tissue to form. But inflammation is often accompanied by pain and swelling, which many people understandably dislike and use ice to dampen.Looking at the mouse leg muscles, the researchers saw clear evidence of damage to many of the muscles’ fibers. They also noted, in the tissue that had not been iced, a rapid muster of pro-inflammatory cells. Within hours, these cells began busily removing cellular debris, until, by the third day after the contractions, most of the damaged fibers had been cleared away. At that point, anti-inflammatory cells showed up, together with specialized muscle cells that rebuild tissue, and by the end of two weeks, these muscles appeared fully healed.Melody Melamed for The New York TimesMelody Melamed for The New York TimesNot so in the iced muscle, where recovery seemed markedly delayed. It took seven days in these tissues to reach the same levels of pro-inflammatory cells as on day three in the unchilled muscle, with both the clearance of debris and arrival of anti-inflammatory cells similarly slowed. Even after two weeks, these muscles showed lingering molecular signs of tissue damage and incomplete healing.The upshot of this data is that “in our experimental situation, icing retards healthy inflammatory responses,” says Takamitsu Arakawa, a professor of medicine at Kobe University Graduate School of Health Sciences, who oversaw the new study.But, as Dr. Arakawa points out, their experimental model simulates serious muscle damage, such as a strain or tear, and not simple soreness or fatigue. The study also, obviously, involved mice, which are not people, even if our muscles share a similar makeup. In future studies, Dr. Arakawa and his colleagues plan to study gentler muscle damage in animals and people.But for now, his study’s findings suggest, he says, that damaged, aching muscles know how to heal themselves and our best response is to chill out and leave the ice packs in the cooler.

SharecloseShare pageCopy linkAbout sharingimage copyrightGetty ImagesAustralia has been one of the world’s success stories in its fight against Covid-19, but frustration is growing over its delayed vaccination rollout. The country has been slower than most others to immunise its population, with some high-risk groups crying out for protection.Last month, it fell 85% short of its own target – and the lack of clarity around the process has been criticised.Supply shortages and delivery problems have been blamed for the delays.And while steps have been taken to speed up the programme – such as mass immunisation hubs and investment in local production – the government is seeing its success so far in battling Covid tarnished by its sluggish vaccination effort. How many Australians have been vaccinated? The rollout began in February and so far 1.6 million vaccine doses have been administered nationwide in a population of 25 million. That’s well short of the four million dose goal originally set for March. After initially saying all Australians would be fully vaccinated by October, the government kept pushing its timeline. Now, it’s scrapped its target altogether. Prime Minister Scott Morrison said given the “many uncertainties involved” it was no longer possible to set an end-of-year vaccination goal.Covid map: Where are cases the highest?Australian PM is vaccinated as rollout begins’I grew up in a war – I’m not dying in a pandemic’Right now, Australia is in the initial phases of a staged rollout. Doses are currently being offered to people over 70, those in aged care homes, frontline health workers, emergency services workers, Aboriginal and Torres Strait Islander people over 55, and people with underlying health conditions.Still, many in those high-risk groups in the aged care and disability sector say they haven’t received doses. image copyrightGetty ImagesLast week, disability services provider Aruma, which runs about 350 group homes for people with severe disabilities, told the ABC that none of its residents or staff members had been vaccinated.A survey of 254 aged care workers by the United Workers Union found that 85% hadn’t even received their first dose.”Too much confusion… limited information from government,” one aged care worker from South Australia said. “I do not know of one single person or resident that has had a Covid shot.” How does Australia compare globally? A strict policy of lockdowns, border closures and quarantine controls has seen Australia keep infection levels low. The country has recorded 910 deaths and 29,559 cases since the pandemic began – far fewer than many other nations. On the vaccination front, however, it remains a laggard. According to the latest Our World data, Australia has delivered 6.2 doses per 100 people.That rate compares to 67.5 doses per 100 people in the UK, 63.3 in the US, and 26.7 in Germany. Australia is one of the worst performers in the Organisation for Economic Co-operation and Development (OECD), with only Japan, New Zealand and South Korea holding lower vaccination rates per 100 people.Why have there been delays?A big part of the problem has been access to supplies. Australia’s programme is most reliant on the AstraZeneca shot, though Pfizer and Novavax will also be a part of its larger rollout. The country’s initial efforts in securing vaccines appeared promising. It was among the first to announce an order with AstraZeneca, and also trumpeted its local manufacturing capacity with medical firm CSL.Early in the rollout, though, confusion over just how much stock Australia had began to circle. A tussle with the European Union led to part of the AstraZeneca order being held back. And a lack of clear, public information has made it difficult to assess supply levels. At the same time, domestic production hasn’t lived up to expectations. Manufacturing began in March, with the government saying it would soon pump out about one million doses a week. It has so far failed to hit those targets. Then, issues around a rare blood clotting disorder associated with the AstraZeneca jab, made the situation worse. A woman in her 40s, who had underlying health conditions, developed blood clots and later died after receiving the vaccine. The government now recommends people under 50 get a Pfizer vaccine. It has said Australia will receive 40 million doses of the Pfizer jab this year, but it’s unclear how many doses are available right now. image copyrightGetty ImagesNovavax, the last vaccine in the rollout mix, is yet to receive regulatory approval. Are there any other issues?Concerns about the AstraZeneca vaccine – the biggest part of its rollout plan – slowed things down and also contributed to some vaccine hesitancy. Supplies have also been an issue. Doctors administering vaccines at clinics have spoken out about shortages, while the nation’s general practitioners’ (GP) union had also raised concerns.AstraZeneca: Is there a blood clot risk?At the same time, state and federal government have argued over who is to blame for the delays. Two state governments – New South Wales and Queensland – have accused the federal government of failing to provide certainty over how many vaccines would be delivered. This, in turn, has slowed down scheduling appointments. There are reports of patients across Australia having difficulties booking slots. What is being done to speed up the rollout? The government says things are picking up. The health minister has boasted of a six-fold increase in total vaccinations in roughly a month since the GP rollout began. Mass vaccination centres have been opened to speed up delivery. More local production is also possible. The state of Victoria will inject A$50m toward a production facility to make mRNA vaccines – like the Pfizer jab – locally. Still, any facility would require much more funding and it would take at least a year before any doses could realistically be manufactured.What are the wider implications of the delays? Beyond the health concerns, the delay risks economic and social damage. While Australia has fought the battle against Covid in part due to hard border policies, vaccines have been held up as key to unlocking the gates once more. Sectors like tourism and aviation are relying on high levels of immunisation to revive business. Failure to get there risks jeopardising the newly opened Australia-New Zealand travel bubble, along with other potential travel hubs with countries such as Singapore. Australians stranded abroad, already struggling to make it home, may find it even more difficult to do so.

Federal regulators on Wednesday issued highly critical findings from their inspection of a Baltimore plant that was forced to throw out up to 15 million doses of Johnson & Johnson’s coronavirus vaccine and ordered to temporarily stop all production.The Food and Drug Administration cited a series of shortcomings at the massive plant, which is operated by Emergent BioSolutions. The inspection was triggered by reports that Emergent workers had contaminated a batch of Johnson & Johnson doses with the virus used to make AstraZeneca’s vaccine, which is also manufactured there.The violations included failure to properly disinfect the factory and its equipment, as well as failure to follow procedures designed to prevent contamination of doses and to ensure proper strength and purity of the vaccine manufactured there. In a 12-page report, the inspectors cited a total of nine violations, ranging from the design of the building to improperly trained employees. The inspection was finished on Tuesday.In a statement, the F.D.A. noted that it has not authorized Emergent to distribute any doses of Johnson & Johnson vaccine, and that no vaccine manufactured at the plant has been released for use in the United States.AstraZeneca’s vaccine is not yet authorized for use in the United States, and all the Johnson & Johnson doses that have been administered in the country so far were manufactured overseas. At the agency’s request, all production at the factory has been halted.“We will not allow the release of any product until we feel confident that it meets our expectations for quality,” the statement from Dr. Janet Woodcock, the F.D.A.’s acting commissioner, and Dr. Peter Marks, the agency’s top vaccine regulator, said.The agency said it was working with Emergent to fix the problems.

A coroner has called for a change in the law after air pollution led to the death of a nine-year-old girl.Ella Adoo-Kissi-Debrah, who lived near the South Circular Road in Lewisham, south-east London, died in 2013.Responding to the report, Ella’s mother Rosamund Adoo- Kissi-Debrah told the BBC:”All children have a right to breathe clean air, no matter where they live, or where they come from”.

Shift-work and irregular work schedules can cause several health-related issues and affect our defence against infection, according to new research from the University of Waterloo.
These health-related issues occur because the body’s natural clock, called the circadian clock, can be disrupted by inconsistent changes in the sleep-wake schedule and feeding patterns often caused by shift work. To study this, researchers at Waterloo developed a mathematical model to look at how a disruption in the circadian clock affects the immune system in fighting off illness.
“Because our immune system is affected by the circadian clock, our ability to mount an immune response changes during the day,” said Anita Layton, professor of Applied Mathematics, Computer Science, Pharmacy and Biology at Waterloo. “How likely are you to fight off an infection that occurs in the morning than midday? The answer depends on whether you are a man or a woman, and whether you are among quarter of the modern-day labour force that has an irregular work schedule.”
The researchers created new computational models, separately for men and women, which simulate the interplay between the circadian clock and the immune system. The model is composed of the core clock genes, their related proteins, and the regulatory mechanism of pro- and anti-inflammatory mediators. By adjusting the clock, the models can simulate male and female shift-workers.
The results of these computer simulations conclude that the immune response varies with the time of infection. Model simulation suggests that the time before we go to bed is the “worst” time to get an infection. That is the period of the day when our body is least prepared to produce the pro- and anti-inflammatory mediators needed during an infection. Just as importantly, an individual’s sex impacts the severity of the infection.
“Shift work likely affects men and women differently,” said Stéphanie Abo, a PhD candidate in Waterloo’s Department of Applied Mathematics. “Compared to females, the immune system in males is more prone to overactivation, which can increase their chances of sepsis following an ill-timed infection.”
The study, Modeling the circadian regulation of the immune system: sexually dimorphic effects of shift work, authored by Waterloo’s Faculty of Mathematics’ Layton and Abo, was recently published in the journal PLoS Computational Biology.
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