Culture

At high concentrations, reactive oxygen species - known as oxidants - are harmful to cells in all organisms and have been linked to ageing. But a study from Chalmers University of Technology, Sweden, has now shown that low levels of the oxidant hydrogen peroxide can stimulate an enzyme that helps slow down the ageing of yeast cells.

One benefit of antioxidants, such as vitamins C and E, is that they neutralise reactive oxygen species - known as oxidants - which may otherwise react with important molecules in the body and destroy their biological functions. Larger amounts of oxidants can cause serious damage to DNA, cell membranes and proteins for example. Our cells have therefore developed powerful defence mechanisms to get rid of these oxidants, which are formed in our normal metabolism.

It was previously believed that oxidants were only harmful, but recently we have begun to understand that they also have positive functions. Now, the new research from Chalmers University of Technology shows that the well-known oxidant hydrogen peroxide can actually slow down the ageing of yeast cells. Hydrogen peroxide is a chemical used for hair and tooth whitening, among other things. It is also one of the oxidants formed in our metabolism that is harmful at higher concentrations.

The Chalmers researchers studied the enzyme Tsa1, which is part of a group of antioxidants called peroxiredoxins.

"Previous studies of these enzymes have shown that they participate in yeast cells' defences against harmful oxidants," says Mikael Molin, who leads the research group at Chalmers' Department of Biology and Biological Engineering. "But the peroxiredoxins also help extend the life span of cells when they are subjected to calorie restriction. The mechanisms behind these functions have not yet been fully understood."

It is already known that reduced calorie intake can significantly extend the life span of a variety of organisms, from yeast to monkeys. Several research groups, including Mikael Molin's, have also shown that stimulation of peroxiredoxin activity in particular is what slows down the ageing of cells, in organisms such as yeast, flies and worms, when they receive fewer calories than normal through their food.

"Now we have found a new function of Tsa1," says Cecilia Picazo, postdoctoral researcher at the Division of Systems and Synthetic Biology at Chalmers. "Previously, we thought that this enzyme simply neutralises reactive oxygen species. But now we have shown that Tsa1 actually requires a certain amount of hydrogen peroxide to be triggered in order to participate in the process of slowing down the ageing of yeast cells."

Surprisingly, the study shows that Tsa1 does not affect the levels of hydrogen peroxide in aged yeast cells. On the contrary, Tsa1 uses small amounts of hydrogen peroxide to reduce the activity of a central signalling pathway when cells are getting fewer calories. The effects of this ultimately lead to a slowdown in cell division and processes linked to the formation of the cells' building blocks. The cells' defences against stress are also stimulated - which causes them to age more slowly.

"Signal pathways which are affected by calorie intake may play a central role in ageing by sensing the status of many cellular processes and controlling them," says Mikael Molin. "By studying this, we hope to understand the molecular causes behind why the occurrence of many common diseases such as cancer, Alzheimer's disease, and diabetes shows a sharp increase with age."

The fact that researchers have now come a step closer to understanding the mechanisms behind how oxidants can actually slow down the ageing process could lead to new studies, for example looking for peroxiredoxin-stimulating drugs, or testing whether age-related diseases can be slowed by other drugs that enhance the positive effects of oxidants in the body.

More about: The mechanism of slowed ageing by the enzyme Tsa1:

The Chalmers researchers have shown a mechanism for how the peroxiredoxin enzyme Tsa1 directly controls a central signalling pathway. It slows down ageing by oxidising an amino acid in another enzyme, protein kinase A, which is important for metabolic regulation. The oxidation reduces the activity of protein kinase A by destabilising a portion of the enzyme that binds to other molecules. Thus, nutrient signalling via protein kinase A is reduced, which in turn downregulates the division of cells and stimulates their defence against stress.

More about: Related results from other research groups:

Other studies have also shown that low levels of reactive oxygen species can be linked to several positive health effects. These oxidants are formed in the mitochondria, the 'powerhouse' of a cell, and the process, called mitohormesis, can be observed in many organisms, from yeast to mice. In mice, tumour growth is slowed by mitohormesis, while in roundworms it has been possible to link both peroxiredoxins and mitohormesis to the ability of the type 2 diabetes drug metformin to slow cellular ageing.

Metformin is also relevant in the hunt for drugs that can reduce the risk of older people being severely affected by Covid-19. Studies in China and the United States have yielded some promising results, and one theory is that metformin may counteract the deterioration of the immune system caused by ageing.

VANCOUVER, Wash. - Workers experiencing job and financial insecurity are less likely to follow the CDC's guidelines for COVID-19, such as physical distancing, limiting trips from home and washing hands, according to a Washington State University study.

The researchers, who surveyed 745 workers in 43 states, also found that state unemployment benefits and COVID-19 policies affected the connection between economic concerns and compliance with COVID-19 precautions.

The study shows that a scarcity mindset can play a role in how well people are able to focus on responding to the pandemic, said Tahira Probst, a WSU psychology professor and lead author in the study published recently online in the Journal of Applied Psychology.

"We all have a finite set of resources at our disposal, whether it's money, time or social support, and individuals who have fewer of those resources appear less able to enact the CDC-recommended guidelines," said Probst. "The extent to which economic stressors will impact that behavior is in part a function of where we live. Having a fall back, a strong safety net to catch you, seemed to help mitigate the risk factors of job insecurity that was otherwise associated with less adherence to the guidelines."

In states with lower unemployment benefits, job insecurity was associated with a 7% decline in compliance with COVID-19 prevention behaviors.

State-imposed COVID-19 mandates also had a positive effect on compliance but seemed to primarily benefit the financially secure workers more. In states that had fewer restrictions on behavior that could spread the disease, workers were less likely to follow the CDC's recommendations, whether the respondents were financially secure or insecure.

However, in states with a stronger response, including measures such as stay-at-home orders and shutting down non-essential businesses, financially secure employees had 13% higher enactment of the prevention behaviors compared to workers who felt more financially insecure.

These differences could have significant public health ramifications, the authors argue, since research suggests that even modest reductions in social contacts among adults can reduce infection and eventual death rates.

"It's important to acknowledge as a society that there are certain segments of the population, namely the economically secure, that are better equipped to follow the CDC recommendations to prevent the spread of COVID-19," said Probst. "This is a red flag since precarious work and financial strain can also co-occur with other COVID-19 risk factors and pre-existing health disparities."

The researchers recruited survey participants using Amazon's Mechanical Turk, an online crowdsourcing platform. The authors acknowledge that the demographics of that sample skewed more male, 62%, and more college-educated, 68%, than the general U.S. population which is about 50% male and 35% college-educated. However, using the platform did allow the researchers to survey groups of workers representing most states in the U.S. The respondents' median household income of $50,000-$59,000 was also close to that of the United States' median of $60,293.

The data for this study were collected in April, the month after the World Health Organization officially declared the pandemic on March 11. Probst and her colleagues are continuing to follow up with this survey group every 1-2 months to collect a total of seven waves of survey data. The researchers are looking to see if the disparities related to economic stress and protective behaviors translate into greater COVID-19 infection rates.

Bologna, Italy and Huntingdon Valley, Pa. -- Menarini Silicon Biosystems, the pioneer of liquid biopsy technology, today announced the publication of a research study providing support for the reliability of using circulating tumor cell (CTC) count to guide frontline therapy choice for patients with estrogen receptor-positive (ER+), HER2-negative (HER2) metastatic breast cancer. Published in the November issue of JAMA Oncology, this is the first study to support clinical utility of CTC count in a randomized clinical trial.

"Based on our research, the use of the CTC count represents the first objective and reproducible decision tool to help physicians choose between hormone therapy or chemotherapy for this particular group of patients," said lead author Francois-Clement Bidard, MD, PhD, Professor of Medical Oncology at Institut Curie and University of Versailles. "Furthermore, our results indicate that the CTC count complements but does not duplicate the physician's opinion on which treatment to choose and should be included in the decision algorithm. This CTC test may help customizing treatment decisions for all women suffering from ER+ HER2- metastatic breast cancer."

The randomized Phase III trial, known as the STIC CTC study, included 778 women with Stage 4 ER+, HER2- breast cancer and compared the outcomes of treatment decisions based on physician assessment vs. CTC count. Half of the patients were randomly assigned to the clinically driven treatment group, where treatment was selected by a physician based on clinical factors. The other half were assigned to a CTC-driven treatment group, in which patients with 5 or more CTCs in 7.5 mL of blood received chemotherapy, and those with less than 5 CTCs in 7.5 mL received hormone therapy. Menarini Silicon Biosystems' CELLSEARCH® CTC System was used to capture and isolate tumor cells circulating in the blood in all patients.

The results supported the reliability and clinical utility of using the CTC count to guide front line therapy choice. For most patients in the clinically driven arm, the CTC count correlated with the physician's choice of treatment. In the CTC-driven group, escalation of treatment to frontline chemotherapy for patients with high CTC count significantly improved progression free survival (PFS), while de-escalation to hormone therapy for patients with low CTC count did not have a detrimental impact on PFS or overall survival (OS).

"The results of the STIC CTC study provide evidence that the CTC count can support physicians when making effective treatment decisions," said Fabio Piazzalunga, President and CEO of Menarini Silicon Biosystems. "As a company, we will continue to support research aimed at demonstrating the clinical utility of CTC and we maintain our commitment to improve patient management."

Since the trial began, the introduction of CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) in combination with endocrine therapy as a frontline option has changed the treatment algorithm for patients with ER+ HER2- metastatic breast cancer. As a result, Menarini Silicon Biosystems has now been asked to support the analysis of CTC count in an ongoing phase III study known as AMBRE, promoted by Unicancer, the only French hospital network entirely devoted to fighting cancer, and conducted within the French breast cancer intergroup (UCBG) network. The study (NCT04158362) compares chemotherapy and a combination of endocrine therapy with one of the new CDK4/6 inhibitors (abemaciclib) as the initial treatment for metastatic ER+/HER2- breast cancer with high tumor burdend.

Research has confirmed the nationwide Alert Level 4 COVID-19 lockdown had a significant toll on New Zealanders' well-being, especially for younger people - but the results were not all negative.

Researchers from the University of Otago conducted a demographically representative survey of adult New Zealanders between 15 and 18 April, corresponding to days 19 to 22 of the 33-day lockdown.

They found almost a third of participants experienced mental distress during the lockdown, but that many people also experienced some form of 'silver linings'.

They asked Kiwis about their levels of stress, anxiety and depression, about the state of their family relationships and whether there were any positive outcomes from lockdown.

Dr Susanna Every-Palmer, the Head of the Department of Psychological Medicine at the University of Otago, Wellington, says 30 per cent of those surveyed reported moderate to severe psychological distress and 16 per cent had moderate to high levels of anxiety. Almost 40 per cent said their level of well-being was low.

"New Zealand's lockdown successfully eliminated COVID-19 from the community, but our results show this achievement brought a significant psychological toll," Dr Every-Palmer says.

"Substantially increased rates of distress were seen among those who reported having lost their jobs or experienced a reduction in work as a result of the pandemic, those who had potential vulnerabilities to COVID-19, or identified their health status as poor, and those who had a past diagnosis of a mental illness."

The level of mental distress was much higher in younger adults, with almost half of those aged between 18 and 24 experiencing moderate to severe psychological distress compared to less than one in 10 adults aged 65 years and older.

Dr Every-Palmer says the lower level of mental distress among older people likely results from higher baseline levels of well-being. It may also reflect the resilience they have developed through overcoming past adversities and the fact that they were experiencing fewer daily disruptions and economic impacts as a result of lockdown.

"Older people may also have felt they were safer in New Zealand than elsewhere."

Just over six per cent of participants reported having suicidal thoughts during lockdown, although for most this was not a new experience, with 83 per cent saying they had similar thoughts in the 12 months prior to lockdown.

Almost one in 10 participants directly experienced some form of family harm over the lockdown period, including sexual assault, physical assault, or harassment, and threatening behaviour. This is three to four times higher than that reported in the 2018-2019 NZ Crime and Victims of Crime Survey. Reports from China, the US, Brazil and Australia also indicate increases in family violence coinciding with lockdown orders.

Dr Every-Palmer says not all the consequences of the lockdown were negative, with 62 per cent of respondents saying they enjoyed the 'silver linings' experienced during lockdown, including working from home, spending more time with family, and living in a quieter, less polluted environment.

"People reported taking the opportunity to pause, reflect, consider priorities, recreate healthy habits, and they appreciated the environmental benefits brought by reduced travel."

Dr Every-Palmer says the study is unique in international terms, with researchers able to conduct the survey during a stringent lockdown but in the absence of widespread direct effects of the virus.

"It is clear that the consequences of the pandemic will be pervasive and prolonged. Our findings emphasise the need to put resources into supporting mental well-being both during and after lockdowns.

"Governments should make providing mental health support a similar priority to other health measures, such as contact tracing, provision of personal protective equipment and procurement of ventilators."

Supporting the population's psychological well-being includes ensuring people have ready access to accurate information, basic necessities and community connection as well as specialist mental health services, she says.

"Free access to high quality e-therapies and telehealth support also becomes increasingly important if people are afraid or are not allowed to leave their homes."

Fast facts:

Planetary habitability, defined by a planet's ability to sustain liquid water on its surface, is one of the most important concepts in exoplanet science.

Exoplanets (planets that orbit stars outside of our solar system) are subject to space weather in the form of stellar flares, emissions of radiation from stars.

These emissions consist of extreme ultraviolet (XUV) photons and charged particles and can alter the upper atmosphere of the exoplanet. Current methods to determine a planet's ability to support life do not take stellar activity into consideration.

Abu Dhabi, UAE, November 9, 2020: In a new study researchers, led by Research Scientist Dimitra Atri of the Center for Space Science at NYU Abu Dhabi (NYUAD), identified which stars were most likely to host habitable exoplanets based on the calculated erosion rates of the planetary atmospheres.

In the paper titled Stellar flares versus luminosity: XUV-induced atmospheric escape and planetary habitability, published in the journal Monthly Notices of Royal Astronomical Society: Letters, Atri and graduate student Shane Carberry Mogan present the process of analyzing flare emission data from NASA's TESS (Transiting Exoplanet Survey Satellite) observatory.

It was found that more frequent, lower energy flares had a greater impact on an exoplanet's atmosphere than less frequent, higher energy flares. The researchers also determined how different types of stars extreme ultraviolet radiation (XUV) through stellar flares, and how nearby planets are affected.

The ability to sustain an atmosphere is one of the most important requirements for a habitable planet. This research provides new insights into the habitability of exoplanets, as the effects of stellar activity were not well understood. This study also highlights the need for better numerical modeling of atmospheric escape - how planets release atmospheric gases into space - as it can lead to the erosion of atmosphere and the diminishment of the planet's habitability.

"Given the close proximity of exoplanets to host stars, it is vital to understand how space weather events tied to those stars can affect the habitability of the exoplanet," said Atri. "The next research step would be to expand our data set to analyze stellar flares from a larger variety of stars to see the long-term effects of stellar activity, and to identify more potentially habitable exoplanets."

Public health agencies across the UK should launch a National Covid-19 Resilience Programme to support older people through the pandemic and to keep them healthy and resilient over the winter - that's the recommendation from a leading group of scientists and clinicians working in the fields of physiology, nutrition and physiotherapy.

The recommendation will be made in a new report by The Physiological Society and Centre for Ageing Better to be launched this Monday at a meeting of Parliamentary and Scientific Committee (1). The Expert Panel for the project brought together 20 leading scientists and clinicians. (2)

New polling carried out by YouGov for the project found that almost 1 in 3 older people did less physical activity during the first lockdown in March. Of those, 43% said that this was because they no longer had a reason, or had less reason, to get out of the house and be active; 32% were worried about catching Covid-19; and 29% reported lacking motivation to exercise. (3)

Physical activity is an important factor in staying healthy and resilient. Home confinement in older people will be associated with muscle loss, body fat gain and the development of insulin resistance, which are driving factors in the development of weakness and Type 2 diabetes. These changes happen within days if inactivity is marked. This could have dramatic functional consequences for older people, perhaps tilting the balance from being just able to do something, such as rise from a chair, to not.

Increased risks of Covid-19 hospitalisation, disease severity and death are associated with a high body mass index and frailty in older people. Therefore, it is essential to support older people in staying fit and healthy during lockdown to improve their resilience to Covid-19.
A National Covid-19 Resilience Programme would bring together a package of measures to support older people through the lockdown and beyond, keeping them healthy and resilient over the winter. The Government should repeat the approach taken at the start of the first national lockdown in March to identify and proactively contact those at highest risk to offer support and advice (4).

A National Covid-19 Resilience Programme should include:

A tailored exercise programme, focused on older people with key Covid-19 risk factors (obesity, type 2 Diabetes, cardiovascular disease, and sarcopenia). This can draw on existing programmes such as "Make Movement Your Mission"; (http://www.facebook.com/groups/MakeMovementYourMission);

Clear guidance about the importance of a healthy balanced diet containing sufficient levels of protein and appropriate energy content;

Enhance mental health through the creation of virtual communities to counter social isolation;

Enlist help of relatives and volunteers to support behaviour change among older people.

This programme should be supported by a digital platform and by national broadcasters such as through regular televised activity classes on the BBC.

Professor Paul Greenhaff, University of Nottingham, UK and Expert Panel Co-Chair said:

"With England now in its second lockdown it is likely that people across the country will be less physically active. Physical activity is an important factor in staying healthy and resilient and will help protect against risks from Covid-19.

"Lockdowns, while important to reduce transmission of Covid-19, can have a detrimental effect on both the physical and mental health of older people. These changes happen rapidly: within 3 days of not using muscles, people can experience significant decreases in muscle mass and quality which might be the difference of an older people being able to get out of a chair by themselves or not.

"We are calling on public health agencies to urgently address this by launching a National Covid-19 Resilience Programme to support older people through the pandemic. Older people need clear, tailored guidance, about how to keep healthy and resilient, that covers physical activity, nutrition and mental wellbeing.

"Older people are facing this lockdown as the days are getting shorter and colder and therefore we must all re-double efforts to keep older people healthy."

Dr Alison Giles, Centre for Ageing Better, and Expert Panel Co-Chair said:

"As this report highlights, coronavirus lockdowns can be particularly challenging for older people as they can exacerbate a variety of health issues, such as cardiorespiratory deconditioning and weight gain, as well as increased loneliness and social isolation.

"As the country enters a second national lockdown it's important to acknowledge that blanket advice based on age can lead people to feel that they don't have control over managing their own health and risk around COVID-19.

"A National Covid-19 Resilience Programme would give older people more control and offer guidance on how to take care of themselves as the pandemic continues. We must provide people with tools that will allow them to make their own informed decisions on their health, wellbeing and resilience."

A researcher from University of Southern California published a new paper in the Journal of Marketing that explores whether attractive food might seem healthier to consumers. The study forthcoming in the Journal of Marketing is titled "Pretty Healthy Food: How and When Aesthetics Enhance Perceived Healthiness" and is authored by Linda Hagen.

Consumers see almost 7,000 food and restaurant advertisements per year, with the vast majority touting fast food. In marketing materials, food is extensively styled to look especially pretty. Imagine the beautiful pizza you might see on a billboard--a perfect circle of crust with flawlessly allocated pepperoni and melted cheese. Advertisers clearly aim to make the food more appetizing. But do pretty aesthetics have other, potentially problematic, effects on your impressions of food?

On one hand, beautiful aesthetics are closely associated with pleasure and indulgence. Looking at beautiful art and people activates the brain's reward center and observing beauty is inherently gratifying. This link with pleasure might make pretty food seem unhealthy, because people tend to view pleasure and usefulness as mutually exclusive. For instance, many people have the general intuition that food is either tasty or healthy, but not both.

On the other hand, a specific type of aesthetics called "classical" aesthetics is characterized by the ideal patterns found in nature. For instance, a key classical aesthetic feature is symmetry, which is also extremely common in nature. Another prominent classical aesthetic feature involves order and systematic patterns, which, again, are ubiquitous in nature. It seems possible that sporting more of these nature-like visual features might make food depictions feel more natural. Seeming more natural, in turn, may make the food seem healthier because people tend to consider natural things (e.g., organic food or natural remedies) to be healthier than unnatural things (e.g., highly processed food or synthetic chemicals). So, by virtue of reflecting nature, the same food may seem healthier when it is pretty (compared to when it is ugly).

In a series of experiments, the researcher tested if the same food is perceived as healthier when it looks pretty by following classical aesthetics principles (i.e., symmetry, order, and systematic patterns) compared to when it does not. For example, in one experiment, participants evaluated avocado toast. Everyone read identical ingredient and price information, but people were randomly assigned to see either a pretty avocado toast or an ugly avocado toast (the pictures had previously been, on average, rated as differentially pretty). Despite identical information about the food, respondents rated the avocado toast as overall healthier (e.g., healthier, more nutritious, fewer calories) and more natural (e.g., purer, less processed) if they saw the pretty version compared to the ugly version. As suspected, the difference in naturalness judgments drove the difference in healthiness judgments. Judgments of other aspects, like freshness or size, were unaffected. Experiments with different foods and prettiness manipulations returned the same pattern of results, suggesting that the effect is unlikely idiosyncratic to certain pictures.

Importantly, these healthiness judgments affect consumer behavior. In a field experiment, people were willing to pay significantly more money for a pretty bell pepper than an ugly one, and a substantial portion of this boost in reservation prices was attributable to an analogous boost in healthiness judgments. In another study, even when people had financial incentives to correctly identify which of two foods contained fewer calories, they were more likely to declare a target food to be the lower calorie option when it was pretty than when it was ugly--even though this choice lost them money.

There are some key qualifications. First, the pretty=healthy effect is limited to classical aesthetics. "Expressive" aesthetics do not involve nature-like patterns, but instead please through imaginative execution of creative ideas, such as food cut into fun shapes or arranged to depict a scene. Second, the pretty=healthy bias can be muted by displaying a disclaimer next to the food reminding people that the food was artificially modified.

This effect of classical aesthetic principles has implications for marketers and public health advocates, albeit different ones. Hagen explains that "Classical aesthetics may be a costless and subtle new way to convey naturalness and healthfulness--attributes that consumers increasingly demand in food products. At the same time, pretty food presentation may optimistically distort nutrition estimates and negatively impact dietary decisions. Given these findings, policy-makers may want to consider modification disclaimers as an intervention or strengthen regulations around providing objective nutrition information with food images."

A new study led by Maria Manuel Mota, group leader at Instituto de Medicina Molecular João Lobo Antunes (iMM; Portugal), now shows that malaria parasites secrete the protein EXP2 that is required for their entry into hepatocytes. These findings, published today in the scientific journal Nature Communications*, open a new avenue for prophylactic anti-malarial strategies, since blocking or decreasing the infection of the liver can prevent the disease.

Plasmodium parasites are the causative agents of malaria, one of the most prevalent infectious diseases, that still infect yearly over 200 million people worldwide. After being transmitted, Plasmodium parasites travel to the liver, where they infect its cells, called hepatocytes. It is still largely unknown how parasites invade hepatocytes and consequently, few therapies are available to prevent this initial step. Now, a research team led by Maria Manuel Mota at iMM has discovered that these parasites secrete a protein named EXP2, before invading the hepatocyte, creating pores in the host cell's membrane. "We observed that the Plasmodium parasites, that are called sporozoites at this stage, secrete EXP2 molecules before entering the cell and this protein creates pores in the outer membrane of hepatocytes, facilitating parasite entry. If you image the hepatocyte as a house, the parasites are breaking window- in this case with the EXP2 proteins - to trigger the alarm system of the hepatocytes", explains João Mello-Vieira, PhD student and first author of this work.

EXP2 had been widely studied during the blood stage of infection, where it has a crucial role only after the parasite has established itself inside the red blood cell. However, its role during the liver infection was unclear. Vanessa Zuzarte Luis, senior author of the work explains: "We observed that sporozoites that lack EXP2, are not able to invade hepatocytes. But, if we produce this protein and add it to the cells, the parasites that lack EXP2 are now able to enter cells normally. This created another question: the pores created by EXP2 are not big enough for the parasite to go through them. So, how is EXP2 facilitating invasion?".

Other pathogens, such as adenoviruses, bacteria and another parasite (Trypanosoma cruzi) have been shown to invade using this type of pore-forming proteins. In such cases, the secreted pore-forming proteins, induce a damage in the membrane of the cell, so that the cell actively engulfs the pathogen, as it is repairing the pore. "If we go back to the image of the house, the parasites are breaking the window and using the moment that owner comes out to see who did it, to go in through the door.". We hypothesized that Plasmodium sporozoites induce a similar response. In fact, if we block the key human enzyme for this repair process, acid sphingomyelinase, we can reduce invasion of hepatocytes by sporozoites", adds Vanessa Zuzarte Luis.

On the importance of these results, Maria Manuel Mota states: "Our results hint at the convergent evolution of different pathogens, that evolved a common strategy to hitchhike their way into the cells. It also creates an opportunity for prophylactic interventions. If we are able to block parasite proteins or the repair process, we are able to prevent infection of the liver by Plasmodium parasites, preventing malaria before the parasite can cause any harm. Moreover, if we are able to block EXP2, we might be able to prevent the development of the parasite in the ensuing blood stage."

A genetically edited form of a herpes simplex virus -- rewired to keep it from taking refuge in the nervous system and eluding an immune response -- has outperformed a leading vaccine candidate in a new study from the University of Cincinnati, Northwestern University and the University of Nebraska-Lincoln.

Published Nov. 6 in the journal Nature Vaccines, the study found that vaccinating guinea pigs with the modified live virus significantly increased the production of virus-combating antibodies. When challenged with a virulent strain of herpes simplex virus, the vaccinated animals displayed fewer genital lesions, less viral replication and less of the viral shedding that most readily spreads infection to others.

The modified virus is actually a form of herpes simplex virus type 1, best known for causing cold sores around the lip. The fact that it demonstrated cross-protection against HSV type 2 -- the sexually transmitted type usually responsible for genital herpes -- suggests that an HSV-2-specific edition of the vaccine could prove even more effective, the researchers said.

The World Health Organization estimates that more than 500 million people have HSV-2, which persists for a lifetime and often flares up in response to stress. In addition to causing blisters, HSV-2 increases the risk for HIV infection and may contribute to Alzheimer's disease or other forms of dementia.

Despite the prevalence of the viruses, more than four decades of research have yet to yield an approved vaccine for HSV-1 or HSV-2. Part of the difficulty: The alphaherpesviruses, which include HSV, have evolved an especially sophisticated way of evading the immune responses aimed at destroying them.

After infecting mucosal tissues of the mouth or genitourinary tract, HSV works its way to the tips of sensory nerves that transmit signals responsible for the sensations of pain, touch and the like. With the help of a specialized molecular switch, the virus then breaks into the nerve cell, hitching a ride on the molecular equivalent of a trolley car that transports it along a nerve fiber and into the nucleus of a sensory neuron. Whereas the mucosal infection is soon cleared by the immune response, the infected neurons become a sanctuary from the body's immune system, with HSV leaving only when stirred by rises in steroids or other stress-elevated hormones in the host.

Nebraska's Gary Pickard and Patricia Sollars, alongside Northwestern's Gregory Smith and Tufts University's Ekaterina Heldwein, have spent years studying how to prevent HSV from reaching the safety of the nervous system. Heldwein advanced those efforts when she characterized the architecture of a certain alphaherpesvirus protein, pUL37, that the team suspected was integral to the virus moving along nerve fibers. Computer analyses based on that architecture suggested that three regions of the protein might prove important to the process.

Smith then carefully plucked out and replaced five codons, the fundamental coding information in the DNA, from the viral genome of each region. The researchers hoped that those mutations might help impede the virus from invading the nervous system.

Their hopes were rewarded when Pickard and Sollars injected mice with a virus modified in region 2, or R2, of the protein. Rather than advancing deeper into the nervous system, the virus was stuck at the nerve terminal. But the team also knew that modifying HSV could have unintended consequences.

"You can keep the virus from getting into the nervous system," said Pickard, professor of veterinary medicine and biomedical sciences at Nebraska. "That's not that hard to do by making broadly debilitating mutations. But when you knock down the virus so much that it doesn't replicate well, you are not rewarded with a robust immune response that can protect you from future exposures."

So the researchers were heartened when further studies showed that the R2-mutated virus performed well as a vaccine in mice. Moreover, it circumvented certain stubborn issues that have cropped up with other vaccine approaches. Some approaches have involved challenging the immune system with only a subset of HSV components, or antigens, priming the body to recognize them but potentially miss others. Some have modified the virus so that it can replicate just once, preventing long-term persistence in the nervous system but also reducing spread in mucosal tissues and, by extension, a stout immune response.

"So it's the same story over and over again: Either your subunit vaccine doesn't present enough antigens, or you make the live virus essentially so sick that it doesn't work really well to generate an immune response," Pickard said. "That's why we're so optimistic about our R2 platform, because it avoids all those problems."

David Bernstein, a researcher at Cincinnati Children's Hospital Medical Center who evaluates herpesvirus vaccine candidates through a program supported by the National Institutes of Health, took note of the team's success and reached out to Northwestern's Smith in 2018. Armed with an R2-modified form of HSV-1, Bernstein decided to test its effectiveness against HSV-2 infection in guinea pigs. As promising as their prior results had been, Pickard conceded that he wasn't sure an HSV-1 vaccine would be up to the task of generating immunity against HSV-2.

But just one of the dozen R2-inoculated guinea pigs developed acute lesions after being injected with HSV-2, compared with five of 12 animals receiving another promising vaccine candidate that recently failed a human clinical trial. Whereas that latter vaccine candidate had no discernible effect on the number of days that guinea pigs shed the virus, the team's R2 vaccine cut the shedding period from 29 days to about 13. And unlike the guinea pigs receiving no vaccine or the other candidate, those receiving the R2 vaccine showed no sign of HSV-2 in the cluster of brain cells that normally house it. Neutralizing antibodies, meanwhile, registered about three times higher in the R2-inoculated guinea pigs than in those inoculated with the other vaccine candidate.

"The fact that the viral shedding was knocked down so much with the R2 vaccine is really important, because it's the viral shedding -- even if it doesn't cause lesions -- that can then pass on the virus," Pickard said. "If you have genital herpes, you can pass that on to your significant other, not knowing that you're doing it. It's very problematic. So the fact that the shedding was knocked down so much is a really good sign."

With an HSV-1 version of the R2 vaccine showing such promising cross-protection against its sexually transmitted counterpart, the researchers' to-do list now includes making and testing an HSV-2 vaccine against the HSV-2 virus.

"If you're making antibodies against the proteins of that particular virus, it stands to reason (that) it would work better than if you're making an antibody against something that's slightly different," he said. "So that's our expectation."

'IT'S GOING TO HAVE A BIG IMPACT'

Around the time that Bernstein and his NIH program were expressing interest in the R2 vaccine design, Pickard and Smith were launching a startup, Thyreos LLC, aimed at further developing and eventually licensing their R2 vaccine design.

Fittingly for a couple of researchers based in Nebraska and Illinois, the duo is working on vaccines for livestock -- cattle and hogs, specifically -- that contend with alphaherpesviruses of their own. In cattle, the bovine herpesvirus can cause respiratory disease, curb appetite and even contribute to aborted calves, all of which add up to billions of dollars in lost revenue annually. Though a modified live-virus vaccine for cattle does exist, it also gets into the bovine nervous system. And that, Pickard said, can spell trouble in cattle just as easily as in people.

"What happens, then, is that when those cows are loaded on a truck and shipped to a feedlot, it's a stressful environment," he said. "The virus hiding in the immune system reactivates. They start shedding the virus from excretions in their nose, and they can then pass that virus on to other animals in that feedlot, and the cattle can get respiratory disease.

"So the fact that our R2-modified viruses don't enter the nervous system is not just an academic thing. Actually, it has a real, practical application for the cattle industry."

As they prepare to embark on a new series of studies that they hope will show the R2 design's superiority to the current industrywide vaccine, Pickard and Smith are also kicking off an initial round of seed funding for the enterprise.

Given that the team initially developed its R2 design in the alphaherpesvirus that infects pigs -- the so-called pseudorabies virus -- Pickard also expressed confidence in the design's promise for protecting hogs. In the late 1990s and early 2000s, the United States waged a successful campaign to eradicate pseudorabies from the country, in large part through vaccination. As with cattle, though, the vaccine can enter the nervous system of hogs and has proven less successful in countries that are less vigilant about outbreaks.

"Again, we are pretty confident that our pseudorabies virus R2 vaccine is going to be more effective than what's been out there," Pickard said. "In terms of protecting pigs, it's going to have a big impact at some point.

"These pathogens can survive trans-Pacific transport in feed ingredients or feed products. When you talk to people who are concerned about biosecurity, they say that whatever is going on elsewhere in the world in terms of these viruses, eventually, they may show up here. It's just a matter of time."

A small team of astronomers have found a new way to 'see' the elusive dark matter haloes that surround galaxies, with a new technique 10 times more precise than the previous-best method. The work is published in Monthly Notices of the Royal Astronomical Society.

Scientists currently estimate that up to 85% of the mass in the universe is effectively invisible. This 'dark matter' cannot be observed directly, because it does not interact with light in the same way as the ordinary matter that makes up stars, planets, and life on Earth.

So how do we measure what cannot be seen? The key is to measure the effect of gravity that the dark matter produces.

Pol Gurri, the PhD student at Swinburne University of Technology who led the new research, explains: "It's like looking at a flag to try to know how much wind there is. You cannot see the wind, but the flag's motion tells you how strongly the wind is blowing."

The new research focuses on an effect called weak gravitational lensing, which is a feature of Einstein's general theory of relativity. "The dark matter will very slightly distort the image of anything behind it," says Associate Professor Edward Taylor, who was also involved in the research. "The effect is a bit like reading a newspaper through the base of a wine glass."

Weak gravitational lensing is already one of the most successful ways to map the dark matter content of the Universe. Now, the Swinburne team has used the ANU 2.3m Telescope in Australia to map how gravitationally lensed galaxies are rotating. "Because we know how stars and gas are supposed to move inside galaxies, we know roughly what that galaxy should look like," says Gurri. "By measuring how distorted the real galaxy images are, then we can figure out how much dark matter it would take to explain what we see."

The new research shows how this velocity information enables a much more precise measurement of the lensing effect than is possible using shape alone. "With our new way of seeing the dark matter," Gurri says, "we hope to get a clearer picture of where the dark matter is, and what role it plays in how galaxies form."

Future space missions such as NASA's Nancy Grace Roman Space Telescope and the European Space Agency's Euclid Space Telescope are designed, in part, to make these kinds of measurements based on the shapes of hundreds of millions of galaxies. "We have shown that we can make a real contribution to these global efforts with a relatively small telescope built in the 1980s, just by thinking about the problem in a different way," adds Taylor.

ATLANTA -- New research shows that corticosteroid injections for knee OA treatment do not hasten a patient's progression to a total knee replacement when compared with hyaluronic acid injections. Details of this study was presented at ACR Convergence, the American College of Rheumatology's annual meeting (ABSTRACT #1652).

Osteoarthritis (OA) is a common joint disease that most often affects middle age to older people. It is commonly referred to as "wear and tear" of the joints, but it is now known that OA is a disease of the entire joint, involving the cartilage, joint lining, ligaments, and bone. OA is characterized by breakdown of the cartilage, bony changes of the joints, deterioration of tendons and ligaments, and various degrees of inflammation of the joint lining, or synovium.

The researchers wanted to know if corticosteroid injections for knee OA sped up the progression of the disease, leading to a need for total knee replacement surgery sooner. Recent research suggests that steroid injections have a threefold-higher risk of progression for people with knee OA. However, many patients in this and other studies of corticosteroid therapy have more advanced knee arthritis, which is a risk factor for disease progression in and of itself. To clarify the potential risks of steroid injections for knee OA progression, this new study compared steroid injections to hyaluronic acid injections, which is not associated with cartilage loss.

"The treatment options we have for knee OA are limited. Weight loss can reduce pain from knee OA and delay progression of disease, but this is very difficult for most patients to achieve," says the study's co-author, Justin J. Bucci, MD, assistant professor of medicine at Boston University School of Medicine. "Pain medications cannot be used safely by many patients with OA because of co-existing heart or kidney disease. Steroid injections are considered a safe and effective intervention for relieving pain from knee OA. Recent studies have raised the possibility that steroid injections are associated with progression of OA. Clinicians and patients need to know if steroid injections are making knee OA worse so they can make informed decisions about their treatment."

The researchers used two large cohort studies of people with knee OA who received either corticosteroid or hyaluronic acid injections. They reviewed the rates of radiographic progression, or joint damage seen on X-rays, and total knee replacement surgery. Patients in the first cohort had medical visits every 12 months, and those in the second cohort had visits every 30 months. Their exams included knee X-rays and questions about their steroid or hyaluronic acid injections over the previous six months. Knee OA progression was measured using two standard scores Kellen and Lawrence grades (KL) and medial joint space narrowing, both of which are radiographic measures

When they analyzed X-ray progression, the researchers excluded anyone with a baseline KL 4 score and anyone who had received either corticosteroid or hyaluronic acid injections in the past. They compared X-rays from each patient's medical visits before their first injection to those taken after their last injection. They assigned KL and joint space narrowing scores to each X-ray at medical visits where total knee replacement surgery was prescribed.

In all, the researchers analyzed 792 knees, including 647 treated with corticosteroid injections and 145 with hyaluronic acid injections. They found that the rate of total knee replacement surgery was greater among patients with a single exam where they reported hyaluronic acid injection compared to those with a single exam where they reported corticosteroid injection. They did not find a difference in those patients reporting injections at multiple exams. Further analysis showed similar rates of X-ray progression for both injection treatments at either single or multiple medical exams.

Corticosteroid injections are not associated with higher risk of two key signs of worsening knee osteoarthritis, either radiographic progression or progression to a total knee replacement, compared to hyaluronic acid injections, the study's findings show.

"We did not find any association between steroid injections and worsening knee OA in our study. Patients and clinicians should see this study and feel reassured that these injections are not causing progression of OA or earlier total knee replacement," says Dr. Bucci. His group's future research will focus on magnetic resonance imaging (MRI) of knees undergoing steroid injection treatment for OA. "MRI provides a more detailed look at structures within the knee compared to X-rays and these images were obtained as part of the cohorts we studied. This information will add to the findings from our current study, and give patients and clinicians a better understanding of what happens to knees treated with steroid injections."

ATLANTA -- New research presented at ACR Convergence, the American College Rheumatology's annual meeting, reveals that romosozumab, an osteoporosis drug, produces substantial gains in bone mineral density in the hip and lumbar spine within one year, and that transitioning patients to a potent antiresorptive drug can lead to even more bone density gains (ABSTRACT #1973).

Osteoporosis results from a loss of bone mass, measured as bone mineral density (BMD), and from a change in bone structure. Many factors will raise your risk of developing osteoporosis and breaking a bone. Bone is living tissue that is in a constant state of regeneration. The body removes old bone (called bone resorption) and replaces it with new bone (bone formation).

Earlier studies have shown that another bone building medication, teriparatide, which stimulates both bone formation and bone breakdown, boosts BMD in both the spine and hip when used first, followed by an antiresorptive drug. However, when antiresorptive drugs are given first, particularly bisphosphonates, such as alendronate, and denosumab, the effect of teriparatide is different, and a patient's BMD may decline in their hips.

To find out more about how romosozumab may be given in sequence with different antiresorptive drugs, researchers launched this new study that reviewed results from four recent, large-scale trials.

"Romosozumab exerts a unique mechanism of action on bone tissue. It increases bone formation and decreases bone resorption. When it's given as initial therapy for one year, followed by an antiresorptive medication such as alendronate or densosumab, the treatment sequence significantly increases BMD and reduces fracture risk compared to both placebo and alendronate treatment," says the study's co-author, Felicia Cosman, MD, professor of medicine at Columbia University College of Physician and Surgeons in New York City. "This study was designed to determine if, despite the different mechanism of action for romosozumab versus teriparatide, the effect on BMD would be different when romosozumab was given as the second treatment, after an antiresorptive medication, compared to using romosozumab first."

The researchers found that osteoporosis patients had noticeably different results when romosozumab was administered first, rather than after, an antiresorptive treatment. In the two studies where romosozumab was given first, over the year of romosozumab treatment, patients' total hip BMD increased 6% in one study and 6.2% in the other. In contrast, when they took alendronate first, the total hip BMD increased only 2.9% with romosozumab treatment. When denosumab was given first, the total hip BMD increased only 0.9% with romosozumab administration.

Over two years, when romosozumab was followed by alendronate, the 2-year total hip BMD gain was 7.1% and when romosozumab was followed by denosumab, the 2-year total hip BMD gain was 8.5%. In contrast, with the inverse sequence, when denosumab was given first, followed by romosozumab, the 2-year total hip BMD gain was less than half - only 3.8%.

What about the effect of different treatment sequences on bone density in the lumbar spine? The researchers found similar results here. Over one year, when romosozumab was given first, patients' spine BMD increased 13.7% in one study and 13.1% in the other. When romosozumab was given after alendronate, lumbar spine BMD gain was 9.8%. When romosozumab was given after denosumab, the spine BMD gain was only 5.3%.

Similarly, over two years, when romosozumab was followed by alendronate, two-year spine BMD gain was 15.2%, and when romosozumab was followed by denosumab, two-year spine BMD gain was 16.6%. When denosumab was followed by romosozumab, two-year spine BMD gain was lower, at 11.5%.

Because women who have had recent or multiple fractures in adulthood are at very high risk for more, this data could help both osteoporosis patients and their doctors make more effective preventive treatment choices, says Dr. Cosman.

"These women need medication that can build BMD fast to improve bone strength and reduce the risk of fractures. The standard approach that most health care providers use is to start treatment with antiresorptive medicine. However, bone building agents like romosozumab, abaloparatide and teriparatide reduce fracture risk faster than antiresorptive medicines. There are about two million fractures every year from osteoporosis," she says. "Patients need to know that the best option for them might be to receive a bone building medication first, rather than an antiresorptive treatment."

ATLANTA -- New research shows that children with Kawasaki Disease remain at an increased risk for cardiovascular events more than 10 years after hospitalization for their condition, highlighting the need for long-term heart disease surveillance and risk reduction strategies for these young patients. Details of the study was presented at ACR Convergence, the American College of Rheumatology's annual meeting (ABSTRACT #0937).

Kawasaki disease (KD) is a childhood illness that causes blood vessels to become inflamed (vasculitis) and swell. KD is most common in children younger than five years old; however, older children can be affected too. Its exact cause is unknown. Without prompt medical evaluation and treatment, serious damage to the blood vessels of the heart may develop. KD is associated with coronary artery aneurysms.

Researchers in Ontario, Canada noticed that the incidence of KD has significantly increased in their province over the past two decades. However, the risk of long-term cardiovascular events after childhood KD diagnosis remains unknown. They launched this study to determine the risk and timing of long-term cardiovascular events and death among KD survivors.

"The motivation to perform this study came from a conversation I had with a patient's family as a first-year pediatric resident. Their child had been diagnosed with KD and was almost ready to be discharged from the hospital. They asked me whether their child would be at risk of heart disease later in life," says study co-author Cal Robinson, MD, BSc, Pediatric Nephrology Resident at The Hospital for Sick Children and the University of Toronto. "Not knowing the answer, I dug deeper into the published literature about cardiovascular outcomes after KD and found that a significant knowledge gap existed, particularly in children who did not develop coronary artery aneurysms during their acute illness. It's very important that we better understand the cardiovascular risk after childhood KD. Earlier diagnosis provides opportunities for intervention, which may mitigate the risk of heart disease later in life."

The researchers identified all children up to 18 years of age who survived hospitalization for KD in Ontario between 1995-2018 using health administrative databases. They included only the first eligible hospitalization, excluding children who were previously diagnosed with KD, as well as non-residents of Ontario. They matched each KD case to 100 non-exposed control cases by age, sex and year. They then followed these patients until death or March 2019, or up to 24 years old. They determined the rates of cardiovascular events, major adverse cardiac events (such as heart attack or stroke) and death, comparing children who had KD with those who were not exposed to the disease. They looked specifically at four time periods after hospital discharge: 0-1 year, 1-5 years, 5-10 years and more than 10 years.

They found that, among 4,597 KD survivors, 746 or 16.2% experienced cardiovascular events compared with 5.2% of children without the disease. They also found that 79 or 1.7% experienced major adverse cardiac events compared to 0.7% of children without the disease, and nine died during the median 11-year follow-up period. The most frequent cardiovascular events experienced by KD survivors were ischemic heart disease, arrhythmias, high blood pressure and peripheral vascular disease. KD survivors were at higher risk of heart problems compared to patients who did not have the disease and they experienced cardiovascular events sooner. Their risk was highest in the first year after they were discharged from the hospital. They were also at higher risk of heart surgery like coronary artery bypass grafting. However, their risk of death during follow-up was lower than non-exposed patients.

"Our study results provide a signal that KD survivors have a higher risk of developing heart disease more than ten years after their initial diagnosis. This suggests that KD survivors should be screened at regular intervals for cardiovascular diseases and associated risk factors," says Dr. Robinson. "Cardiovascular risk reduction strategies should be implemented for all KD survivors, including healthy active lifestyle counselling and early intervention when cardiovascular risk factors are identified."

ATLANTA -- A new study shows that patients with rheumatic diseases across Africa, Southeast Asia, the Americas and Europe had trouble filling their prescriptions of antimalarial drugs, including hydroxychloroquine, during the 2020 global coronavirus pandemic, when antimalarials were touted as a possible COVID-19 treatment. Patients who could not access their antimalarial drugs faced worse physical and mental health outcomes as a result. Details of the research was presented at ACR Convergence, the American College of Rheumatology's annual meeting (ABSTRACT #0007).

Systemic lupus erythematosus, also called lupus or SLE, is a chronic (long-term) disease that causes systemic inflammation which can affect multiple organs: the skin, joints, kidneys, the tissue lining the lungs (pleura), heart (pericardium) and brain. Many patients experience fatigue, weight loss and fever. Antimalarial drugs are taken regularly by most people with lupus, as well as many with rheumatoid arthritis (RA) and other rheumatic diseases.

In the early weeks of the global SARS-CoV-2 (COVID-19) pandemic, two antimalarial drugs often used to treat lupus and RA, hydroxychloroquine and chloroquine, were touted to potentially prevent or treat COVID-19 infections. Both drugs were suddenly repurposed as COVID-19 treatments despite a lack of data to support this use, leading to worldwide shortages of both. A team of international researchers launched this study to assess the effects of antimalarials on COVID-19 infection and the impact of drug shortages on people with rheumatic disease.

"The COVID-19 Global Rheumatology Alliance's Patient Experience Survey was launched in April 2020 during the early days of the pandemic, when the scientific and research communities were under extraordinary pressure to identify safe and effective treatments for SARS-CoV-2. Since hydroxychloroquine is an essential treatment for RA and lupus, reported drug shortages of antimalarials became a major concern," says the study's lead author, Emily Sirotich, a doctoral student at McMaster Centre for Transfusion Research in Hamilton, Ontario. and Patient Engagement Lead of the COVID-19 Global Rheumatology Alliance. "The aims of this study were to assess the prevalence and impact of drug shortages during the COVID-19 pandemic, and whether the use of antimalarials in patients with rheumatic disease was associated with a lower risk of COVID-19 infection."

Data for the new study was collected using the COVID-19 Global Rheumatology Alliance Patient Experience Survey. The survey was distributed online through patient support organizations and social media. Both patients with rheumatic diseases and parents of pediatric patients anonymously completed the surveys with information on their rheumatic disease diagnosis, medications they take, COVID-19 status and any disease outcomes. The researchers evaluated the impact of antimalarial drug shortages on patients' disease activity, as well as their mental health and physical health.

Of the 9,393 people who responded to the survey, 3,872 were taking antimalarial drugs and 230 said they were unable to continue taking their medications because of a lack of supply at their pharmacy. Antimalarial shortages were worse for people in Africa and Southeast Asia: 26.7% of respondents in Africa and 21.4% of respondents in Southeast Asia reported inadequate supplies at local pharmacies. Patients in the Americas (6.8%) and Europe (2.1%) also reported being unable to fill their prescriptions at their pharmacy due to lack of supply.

The study found that patients on antimalarials and those who did not take these drugs had similar rates of COVID-19 infection. A total of 28 patients with COVID-19, who were also taking antimalarials, were hospitalized. Of 519 patients diagnosed with COVID-19 in the survey, 68 reported that they were prescribed an antimalarial for their coronavirus infection. Patients who could not fill their antimalarial prescriptions experienced higher levels of disease activity and also experienced worse mental and physical health symptoms, the study found.

"The findings from this study highlight the harmful consequences of repurposing antimalarials, without adequate evidence for benefit, on patients who rely on access to their hydroxychloroquine or chloroquine prescriptions for their rheumatic diseases," says Ms. Sirotich. "It is necessary to maintain scientific rigor even in the context of a pandemic and recognize the potential impacts of drug shortages. It is also important to address regional disparities in access to medications, to ensure all people, particularly those living in developing countries, receive fair and equitable access to their essential medications."

Researchers at the Francis Crick Institute and University College London have found that some antibodies, created by the immune system during infection with common cold coronaviruses, can also target SARS-CoV-2 and may confer a degree of protection against the new viral strain.

In response to infection with a virus, the immune system creates antibodies to help fight it. These antibodies remain in the blood for a period after infection, and in the case of re-infection, they are able to tackle the virus again.

In their paper, published in Science today (Friday 6 November), the scientists found that some people, notably children, have antibodies reactive to SARS-CoV-2 in their blood, despite not ever having being infected with the virus. These antibodies are likely the result of exposure to other coronaviruses, which cause a common cold and which have structural similarities with SARS-CoV-2.

The researchers made this discovery while developing highly sensitive antibody tests for COVID-19. To see how well their assay tests were performing, they compared the blood of patients with COVID-19 to patients who had not had the disease. Surprisingly, they found that some people who had not been exposed to SARS-CoV-2 had antibodies in their blood which would recognise the virus. To confirm their findings, they analysed over 300 blood samples collected before the pandemic, between 2011 and 2018.

Nearly all samples had antibodies that reacted with common cold coronaviruses, which was expected given how everyone has been exposed to these viruses at some point in their lives. However, a small fraction of adult donors, about 1 in 20, also had antibodies that cross-reacted with SARS-CoV-2, and this was not dependent on recent infection with a common cold coronavirus.*

Notably, such cross-reactive antibodies were found much more frequently in blood samples taken from children aged 6 to 16.

Kevin Ng, lead author and post-graduate student in the Retroviral Immunology Laboratory at the Crick says: "Our results show that children are much more likely to have these cross-reactive antibodies than adults. More research is needed to understand why this is, but it could be down to children being more regularly exposed to other coronaviruses.

"These higher levels we observed in children could also help explain why they are less likely to become severely ill with COVID-19. There is no evidence yet, however, that these antibodies prevent SARS-CoV-2 infection or spread."

In the lab, the researchers tested the antibodies they found in blood from uninfected people to confirm they are able to neutralise SARS-CoV-2. They found the cross-reactive antibodies target the S2 subunit of the spike protein on the surface of the virus.

George Kassiotis, senior author and group leader of the Retroviral Immunology Laboratory at the Crick says: "The spike of this coronavirus is made of two parts or subunits, performing different jobs. The S1 subunit allows the virus to latch onto cells and is relatively diverse among coronaviruses, whereas the S2 subunit lets the virus into cells and is more similar among these viruses. Our work shows that the S2 subunit is sufficiently similar between common cold coronaviruses and SARS-CoV-2 for some antibodies to work against both.

"It was previously thought that only antibodies to the S1 could block infection, but there is now good evidence that some antibodies to S2 can be just as effective. This is exciting as understanding the basis for this activity could lead to vaccines that work against a range of coronaviruses, including the common cold strains, as well as SARS-CoV-2 and any future pandemic strains.

"But it is important to stress that there are still many unknowns which require further research. For example, exactly how is immunity to one coronavirus modified by exposure to another? Or why does this activity decline with age? It is not the case that people who have recently had a cold should think they are immune to COVID-19."

A large study is now underway, in partnership with researchers at Imperial College London and University College London, to uncover the role that different antibodies and other immune defences play in protection against COVID-19 and how severely ill people become.