The number of people in England with food allergies has more than doubled between 2008 and 2018, a reveals. The researchers, from Imperial College London, found that rates are highest among preschool children, with 4% having a “probable” food allergy.

They also found that a third of those people at risk of anaphylaxis – a life-threatening allergic reaction – don’t carry adrenaline autoinjector “pens”, such as EpiPens. People in deprived areas were found to be less likely to have been prescribed these life-saving injectors.

The true number of people with food allergies has been difficult to establish, with estimates varying between . This is because several methods are used to estimate the frequency of food allergies, including using either the number of prescriptions of adrenaline pens, self-reporting, or blood tests to identify telltale antibodies.

Self-reporting is the least reliable method because many people confuse food intolerance with allergy, as is evident from a by the UK’s Food Standards Agency.

Of the over 30% of adults who reported an adverse reaction to foods, only 6% were subsequently confirmed to have a true food allergy. To bridge this gap in understanding how common food allergies are, the new study from Imperial College took a much broader approach to better estimate the incidence of food allergy.

Population healthcare data from over 7.5 million people in England and a combination of clinical criteria were used to identify people with food allergies in these health records.

People were considered to have an allergy if doctors indicated they had either had a possible or probable allergy, or if they had been prescribed an adrenaline pen, or both. Using this combination, the number of people with food allergies was shown to have doubled in a decade. Curiously, since 2018, levels have plateaued somewhat at around 4% in preschool children, 2.4% in school-aged children, and under 1% in adults.

The study, published in The Lancet Public Health, used a broad range of criteria to identify people with food allergies. Not all cases were confirmed by medical professionals using additional tests, such as the presence of antibodies in blood or food-challenge tests where people are given increasing amounts of certain foods to see if an allergic reaction occurs.

Some types of food allergy may have been missed, such as . This occurs when people with specific pollen allergies eat some raw foods, including certain stoned fruits, that cause mild irritant symptoms, such as itching of the mouth. Still, there are important questions as to why food allergies have been rising, and why they may now be plateauing.

Puzzling

The trend in the increased rate of allergies in developed countries has puzzled scientists for years. The is one theory that may account for the growing incidence of chronic conditions such as allergies.

This hypothesis considers the role of the microbiome (the collection of helpful bacteria, fungi and viruses that live in and on us), infections and the environment in shaping our immune response and causing it to misfire.

Evidence to support this theory is accumulating. For example, studies show that in early childhood as the immune system and microbiome are developing is linked to a greater likelihood of allergy in later life.

Pollution exposure can also enhance the risk of allergy and .

The food we were exposed to in early life may be important in determining if we develop an allergy. from the UK government about avoiding early exposure to peanuts and eggs may inadvertently be linked to the rise in food allergy to peanuts and eggs.

Conversely, that early exposure before the age of five to is a reduced likelihood of developing an allergy.

The advice in the UK to avoid peanuts and eggs during pregnancy and early childhood was changed in , but the trials showing the positive effects of early exposure to eggs and peanuts were only published in 2015 and 2016. However, it is possible that the plateauing incidence of food allergy cases is linked to changes in advice and the published infant food exposure trials.

Diagnosis is only part of the story. People also need to be able to effectively manage their condition. This requires patients to have access to the right advice and support from experts, such as dietitians, as well as the drugs needed to halt an anaphylactic attack.

For babies diagnosed with a food allergy, there is now ) that incrementally reintroducing the food that causes the allergy can retrain the immune system and might help the child overcome their allergy. However, this must only be done under the guidance of a medical team.

The new study showed that allergy care was largely managed at GP practices in England. However, GP clinics may lack the specialist resources needed for proper allergy support, such as safely re-introducing foods.

It is clear that people in the UK with allergies need better support.

, Professor in Immunology,

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This summer has seen a large – one which is showing potential to be bigger than the 2023 winter wave was.

The current wave has largely been driven by the so-called variants, which have acquired greater immune evasion and ability to enter our cells. The rise in COVID cases has also been a .

COVID is not seasonal, as this current wave is stark evidence of. This is why vulnerable people are given . Nonetheless, most respiratory infections (COVID included) are at . Having access to a COVID booster in the autumn is of great importance, as it protects those who are most vulnerable from severe COVID infections.

The Joint Committee for Vaccination and Immunisation (JCVI) have just published their recommendations for the . Unfortunately, the recommendations they’ve made mean even fewer people will have access to vaccines for free on the NHS this autumn. And, the vaccines that will be made available may not be as effective against the current variants as newer formulations would be. This could leave more patients at risk of potentially serious infection.

The JCVI use a number of considerations in costing their recommendations for vaccine campaigns (although they have not fully released details of their costing model). What is clear is that the main concern is the cost of buying and delivering vaccines to prevent severe disease and deaths.

This year sees even fewer people able to access the vaccine for free on the NHS. The boosters will be offered to those over the age of 65, residents in old-age care homes and people who are at greater risk of catching COVID due to a compromised immune system. The JCVI haven’t advised offering the vaccine to frontline health and social care workers, staff in care homes and unpaid carers or household contacts of immunosuppressed people. Fortunately, the government has agreed to maintain the vaccine this year for .

Reduced vaccine coverage leaves those with regular, close access to vulnerable people unable to reduce their own risk of catching or spreading COVID. Although, it’s possible to purchase vaccines from many pharmacies, this is not cheap – with doses . Many people may not have the resources to pay for one.

Vaccines don’t just lower the risk of severe infection. They may also lower the risk of developing long COVID after an infection . Recent data shows that the risk of developing long COVID from an infection . The most recent Office for National Statistics data also shows are still being reported in the UK. Although fewer new cases are emerging, it’s still a significant number.

Despite the benefit of vaccination on reducing long COVID risk, the JCVI say there’s not enough evidence showing boosters reduce the risk of the condition. This is why they did not into their cost-benefit analysis.

The autumn vaccine campaign will also provide eligible patients with from the Autumn 2023 campaign instead of purchasing new vaccines.

Although using pre-procured doses means less money will be spent on the autumn booster programme, research shows older formulations of vaccines are less effective against variants which emerged after they were developed (such as the ). Modelling suggests they’ll be up to a against severe disease.

Indeed, the , in line with , have recommended boosters be updated to target the JN.1 variants. Several manufacturers have begun preparing updated formulas for . The US’s Food and Drug Administration noted the and requested a modification to vaccines in order to as well.

But even with vaccine modifications being made to it may still be too late, given FLiRT variants are . Recent data suggests the virus is even evolving away from the FLiRT variants with even more .

The fact we’re in a position where we’re using vaccines that may be less effective against current variants is enormously frustrating. Ideally we would be looking to develop or acquire more durable vaccines that confer longer-lasting immunity – such as or that may be more resilient against the ever-evolving virus.

These could potentially have been developed in the UK’s vaccine manufacturing production centre. However, was in 2022. This leaves us lagging well behind other countries, such as , and , which are continuing to invest in developing the next generation of vaccines.

Vaccines, of course, aren’t the only tool we have. We can reduce the impact of infection by widening access to anti-viral COVID drugs (such as Paxlovid). Access to Paxlovid was to be expanded to cover who aren’t eligible for the vaccine (such as people who are obese or have diabetes). But the reality is there aren’t enough supplies and funding to cover the 15 million people that could become eligible – so these plans . Patients currently eligible to access the drug have described difficulty getting hold of this .

Public health measures such as and in buildings could also help lower risk of infection. But again, no money is being invested into making these measures more accessible.

COVID is not just another cold. It still has the potential to cause serious disease – and this threat is not going away anytime soon. Ignoring it isn’t an option, which is why ensuring people still have access to the latest, most effective vaccines is so important.

, Professor in Biomedical Sciences,

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By , and ,

Giant panda reclining in cloudy hills eating bamboo, European bison picking their way through gloomy and lichen-draped forests and Cape mountain zebra roaming arid mountains. Ideas of how and where these species live are fixed in the public imagination, in conservation practice and even in some species’ names – but they may simply be stereotypes.

can develop when research is carried out on a small, biased sample that isn’t representative of a species’ entire natural range. They often give an overly narrow, or just plain wrong, idea of what is needed for survival and breeding.

This problem is particularly acute after range declines, as something can’t be studied where it no longer exists. The idea that the giant panda is so often depicted as eating bamboo may be an artefact of them being rather than a quirk of evolution. In an ideal world, pandas would use a wider range of forest types and have a varied diet much more similar to other bears.

What this means for conservation is that protected areas may not be ideal for the species they are supposedly there to protect.

Similar to the common assumption that pandas prefer to live only on bamboo, there has long been a belief among conservationists that the critically endangered black rhino, given the choice, prefer to eat acacia trees.

But we thought that understanding of black rhino biology, including its diet, could also be a stereotype because habitat loss and the ongoing threat of poaching mean populations are mostly fenced into isolated reserves dotted across the species’ former range.

They are also an excellent test case for busting stereotypes because intensive anti-poaching monitoring has produced some of the most detailed information on births and deaths for any free-living species.

Rhinos struggling in their supposedly ideal habitat

We conducted research in three reserves across the Laikipia plateau in northern Kenya: Lewa, Ol Jogi and Ol Pejeta. This region’s upland savanna ecosystem is exceptional as it has maintained a community of large mammals that can mostly freely migrate. Black rhino however are fixed in place by special fences, and growing numbers mean that . The risk of new populations failing to establish themselves is heightened if the identification of new areas are based on a species stereotype.

Black rhinos are considered to mainly eat trees and to prefer acacia, distinctively thorny and often flat-topped. So when rhinos eat grass it’s taken as an indicator of poor habitat, or of competition with other tree and shrub browsers such as elephants.

The first hint of a stereotype was our finding that females in Ol Jogi have than those in Lewa and Ol Pejeta. This was surprising because Ol Jogi should be an ideal habitat.

The Ol Jogi landscape is classic East African savanna, with rocky outcrops standing proud above wooded grassland. In the dry season the green of the dominant acacia trees stands out against the straw-coloured grass and the red-brown earth. Acacia makes up a higher proportion of the trees here than on the other two reserves, so why should the black rhino population be struggling? By picking up dung and sequencing the plant DNA found within it, we have uncovered .

Rhinos actually prefer grass

The idea for this research was that how an animal’s diet changes from season to season can uncover what its preferred diet would be. For a savanna herbivore, there is far more to eat in the wet season so we expect that they should focus on finding the best food available. In contrast, in the dry season they should eat whatever they can get their teeth into.

In the wet season, we found that black rhino consistently ate less acacia and more grass. The more acacia a rhino ate in the dry season, the larger the shift away from it in the wet season. Together, this suggests that grass is actually a preferred food and acacia functions as a “fallback food”.

Importantly for conservation, females with larger seasonal dietary shifts, which were restricted to acacia in the dry season, bred more slowly. Most of the acacia-eating, diet-shifting, slow-breeding females live on Ol Jogi, whereas rhinos on the other two reserves could consume more grass year-round and breed more often.

The heavy reliance of Ol Jogi rhino on acacia as a fallback food, which leads to slower breeding, and the historically overlooked importance of grass, can at least partly explain why the population does not perform as well. This is crucial for black rhino conservation because habitats are deemed suitable or not largely based on the availability of trees, and particularly acacia.

Conservation may be incorrectly estimating how many rhinos reserves can support, and risk identifying areas where rhino will breed slowly, and be at risk of dying out, as prime habitat. Money and effort may be wasted by trying to conserve this iconic species in the wrong places.

More widely, many species are confined to small parts of their historic range. We cannot just assume that they have clung on in optimal habitat, where they live now may just be a historical accident. Conservation needs to explicitly test where and how species do best, or it may squander its limited resources and the best chances we have to prevent extinctions.

, Postdoctoral researcher, and , University Research Fellow,

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Image credit: Nick Harvey Sky

Hearing loss and dementia both cause difficulties with listening, understanding and communicating. This can lead to breakdowns in relationships because something as simple as a conversation with a loved one can become impossible.

People with dementia often don’t know, or can’t communicate, that they have problems with their hearing. This means that a lot of the time, their carers don’t know either.

Crucially, many people with dementia, and especially those living in care homes, rely on carers to support their hearing needs. This might mean helping with hearing aids or other hearing devices, using communication techniques, writing things down or using flashcards and making sure background noise isn’t too loud.

When hearing care is given properly it can improve residents’ , mood and engagement with peers. Unfortunately, in a new study, my colleagues and I found that only of residents with dementia in UK care homes are given help with their hearing loss.

Poorly supported hearing loss leaves residents at risk of emotional and behavioural problems, worsened confusion and difficulties communicating with important people in their life like family, friends, carers and healthcare professionals. In the same study, just 27% of care staff said that they check that residents’ hearing aids are working properly. This is a huge problem as most residents with dementia aren’t able to do this themselves.

Complicated reasons

The survey results also revealed that the reasons residents with dementia aren’t receiving help with their hearing are complicated. The biggest problem in care homes appears to be access to resources, such as enough time, enough staff or enough things like hearing aid batteries or flashcards. Staff who completed the survey said that not enough resources in the care homes made it difficult to provide hearing-related care to residents with dementia.

Another part of the problem is that care staff don’t always have the relevant knowledge and skills to help residents with their hearing problems. Just under 25% of staff reported having had any training on hearing loss (despite over of residents having hearing loss), but almost all said that they wanted this training to be provided.

Hearing loss isn’t always prioritised in care homes. Compared to dehydration, infections or injuries, hearing and communication problems don’t cause immediate risk or physical harm to residents. So helping residents to hear well isn’t often a priority for staff, who have limited time and a heavy workload. That doesn’t mean that hearing and communicating aren’t essential for a person’s wellbeing and happiness.

Hearing loss isn’t always prioritised.

Results from our survey show that people with dementia living in care homes are not getting the care that they need and deserve to help them to hear, understand and communicate. Care home residents are often very vulnerable, and being able to hear well is essential to maintaining a good quality of life and engaging with .

, Postdoctoral Research Associate,

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There’s a long-held belief that people drink alcohol in excess to drown their sorrows. But into mood and drinking has found the opposite is also true.

Using data from 69 studies (12,394 people in total) in the US, Canada, France and Australia, all of which employed surveys to assess mood and drinking levels, the researchers found no evidence that people drank more on days when they felt down. Rather surprisingly, however, people tended to drink – and drink heavily – on days when they were in a good mood.

The authors found that participants were between 6% and 28% more likely to drink on days they were in a good mood, and 17%-23% more likely to binge drink (having more than four or five drinks within a few hours) on these days.

These findings suggest that, contrary to popular belief, we may actually be more likely to drink in excess when we’re happy than when we’re feeling down. So, what explains this phenomenon? In , we have identified several possible factors.

‘Desire thinking’

Drinking is associated with a thought process called “”. This is a way of thinking that’s geared towards anticipating positive outcomes from certain experiences, based on the associations we have with that experience.

Before we drink, we tend to have an expectation of it based on past experiences – such as how the alcohol will taste, the feeling of being intoxicated, or the idea that alcohol will make us more interesting. We may also have positive memories from other times we drank. If so, the next time we think about having a drink, we may immediately default to thinking of it in a positive light.

This can then lead to “”, where we remind ourselves of the reasons for drinking – such as because you did well at work, or because the weather’s nice. Both this and desire thinking can combine to maintain positive mood and expectations – intensifying the cravings for alcohol.

Adding another layer of positivity to the mix, our research has also found that people tend to hold what we call positive “” regarding the usefulness of desire thinking.

In other words, when desire thinking makes us crave alcohol by reminding us of all the good things that come with drinking, we’re likely to trust that positive thought and see it as a good thing. Thinking positively about the positive experiences we’re about to have may increase our motivation to drink more.

The downside to this potent cocktail of positive thoughts and feelings is that it appears to be incredibly hard to control and resist. For example, there’s evidence that positive beliefs can make us feel like we’re .

Taking control

In our clinical research with and various , we have found that being able to control the way we think about things – whether that thinking is positive or negative – is key to behavioural change and a balanced state of mind.

However, to take control of the way you think about something, you first need to become aware of your extended thought patterns. The better you become at “thinking about your thinking”, the easier it is to control both your positive and negative thoughts.

Let’s say this thought pops into your mind: “I am feeling good – I deserve to drink this weekend.” Instead of thinking more about this, choose to leave the thought alone – a technique called “”. It’s also worth reminding yourself that it’s difficult to if you think about it a lot.

Try to think of the positive and negative thoughts you have as similar to receiving a text message. We don’t always have control over whether the message we receive is good or bad, but we do have complete control over whether we choose to respond to it or not. This will help to show you that you have control over your desire thinking – and therefore your drinking choices.

Positive mood has also been implicated in other addictive behaviours, such as , , and . This tells us that positive mood may not be the pathway to a healthy body and mind, as we might believe.

Instead, what may be important is the ability to be flexible in the way we think and behave around positive and negative moods – and in particular, knowing that we can always make choices in how we behave, regardless of our patterns of thinking.

, Reader in Psychology, Psychotherapy and Counselling, and , Professor of Clinical and Experimental Psychopathology,

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Evidence tells us the COVID pandemic and measures put in place to contain the virus negatively affected the mental health of adolescents and young people in the UK and elsewhere. One published in August 2021 estimated that the global prevalence of children and adolescents with depression and anxiety had doubled since the start of the pandemic.

and typically start during adolescence or early adulthood. As well as being major health issues, both are coping mechanisms that often indicate .

In a , we found that GPs in the UK recorded a large rise in eating disorder diagnoses and self-harm episodes among teenage girls in the first two years of the pandemic.

The study was conducted jointly by the University of Swagֱ��, Keele University, the University of Exeter and the , a mental health research charity. We also worked with an advisory group of young people with lived experience of mental health difficulties, as well as parents and carers.

Comparing predictions and observed case numbers

We used data from the , a database of anonymised primary care electronic health records. We included over 9 million patients aged ten to 24 (both males and females) from 1,881 general practices across the UK.

We calculated the monthly incidence rates of eating disorder diagnoses and self-harm episodes from January 2010 through to March 2022. Based on data from the ten years preceding the pandemic, and using statistical models, we predicted what the rates of eating disorders and self-harm would be had the pre-pandemic trends continued. We then compared the rates actually observed in March 2020 until March 2022 with these predictions.

In the two years after the onset of the pandemic, we found that eating disorder diagnoses were 42% higher than would be expected for girls aged 13–16, and 32% higher for girls aged 17–19. There was little difference between observed and expected incidence for the other age groups.

The increase in rates of self-harm was also greatest among girls aged 13–16, 38% higher than expected. There was no evidence of an increase in self-harm in females in the other age groups.

Among males, the rates of eating disorders and self-harm were lower than, or close to, the expected rates across all age groups.

In the ten years before the pandemic, eating disorder diagnoses in females were more common among those from less-deprived areas than those from more-deprived communities. This socioeconomic difference widened following the onset of the pandemic. Since March 2020, eating disorder diagnoses for females living in the least-deprived communities were 52% higher than expected, compared with 22% higher for those in the most-deprived areas.

In contrast, self-harm rates before the pandemic were higher for those in the most-deprived compared with the least-deprived areas. Since March 2020, self-harm incidence for females in the least-deprived areas was 31% higher than expected, while there was no significant difference between observed and expected incidence for those in the most-deprived areas, therefore narrowing the pre-pandemic gap.

Limitations and possible explanations

Our study is large, but episodes of self-harm that were not treated by health services were not captured in our data, so the rise in self-harm incidence might have been even greater than we observed. However, it’s also possible that cases of self-harm not coming to the attention of services might have exhibited a different pattern.

Previous studies have reported increased hospital admissions and presentations to emergency departments for and symptoms of among teenage girls during the COVID pandemic. Our study complements these findings.

The reasons for the increase in eating disorder diagnoses and self-harm episodes among teenage girls are likely to be complex and could be due to a combination of factors. These include , anxiety resulting from changing routines, disruption to education, unhealthy , and increased awareness of mental health difficulties.

It’s also pertinent to note that youth mental health had been deteriorating even in the years in the UK, though at a less substantial rate of change.

The greater increases in eating disorders and self-harm among female teenagers living in less-deprived areas, relative to those in more-deprived areas, may reflect differences in service provision and access to clinical care between these areas.

What next?

The substantial rise in eating disorder diagnoses and self-harm episodes among teenage girls highlights an urgent need for intervention. Early identification of mental health difficulties in children and young people by primary care clinicians (including GPs, nurses and psychologists) is extremely important, as this facilitates timely access to treatment.

Potential barriers to help-seeking, including and concerns about long waiting lists to access services, need to be tackled. Given the current pressures on the NHS in both primary and specialist care, our study emphasises the need for sufficient capacity in mental health services to meet growing demand.

, Research Fellow, Centre for Pharmacoepidemiology and Drug Safety, and , Research Associate in Epidemiology,

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Fruit flies can be truly annoying when they are buzzing around your living room or landing in your wine. But we have much to thank these tiny nuisances for – they revolutionised biological and medical science.

Flies and mosquitoes both , the group of insects that have only two wings (from the Greek di meaning two and pteron meaning wing). However, just as most people accept the bothersome as well as the positive traits of their friends, we shouldn’t judge flies for their negative behaviour alone.

We should open our eyes to their enormous economic and environmental importance, as entomologist Erica McAlister argues in her book . For example, many plants (including the cacao plant that gives us chocolate) rely on Diptera as pollinators. Or try to imagine a world without flies to decompose dead animals.

I will argue from a different angle, though, to win your respect for one specific dipteran: the fruit or vinegar fly (Drosophila melanogaster).

Drosophila may be smaller than a fingernail but it can be a big nuisance in summer when it hovers over maturing fruit or emerges in swarms from litter bins. The species Drosophila was first mentioned by and has since earned a celebrity status among scientists. It has become the best-understood animal organism on the planet and a powerhouse of modern medical research. Ten scientists working on Drosophila have been awarded a .

Science’s partnership with flies started during the early 1900s when biologist at Columbia University in New York decided to test evolutionary theories, such as how genetic mutations are linked to other characteristics, and the rediscovery in 1900 of theories of inheritance, published 1865. Mendel remains the acknowledged father of genetics today.

Helping science take off

Morgan was to work with Drosophila. But his idea to harness the fly’s cheap husbandry (pieces of banana kept in milk bottles), and rapid reproduction (one generation in about ten days; about 100 eggs per female per day) would make it possible to study evolution in the laboratory. This is because it’s easier to see evolutionary changes in large populations of a species with high turnover.

His mass-breeding experiments with hundreds of thousands of flies led to the discovery of a single fly with white eyes, instead of the red eyes fruit flies normally have. Morgan and his team’s subsequent studies of its white-eyed progeny revealed that genes can mutate and are and (a long DNA molecule). This new understanding founded the field of classical genetics as we know it. For example, it

In the 1940s, scientists, including George Beadle and Edward Tatum, established that can and produce the molecules needed in cells.

Other researchers with fruit flies mapped the structure of the . Through these developments, long-debated questions came into focus. For example, how genes regulate complex biological processes, such as the development of an entire organism from a single fertilised egg cell.

Scientists gradually established techniques using microscopes to study Drosophila embryos in their tiny 0.5mm transparent eggshells. The plethora of genetic strategies we’ve learned about in flies has turned into a powerful means to dissect . Just like human gene mutations can cause body malformations in people, fly embryos also show such defects. For example, lacking their heads or tails.

Scientists can study mutant defects, even if the eggs never hatch, which can then inform us about the normal function of the affected gene. These kinds of genetic studies of Drosophila, combined with emerging technologies, such as gene cloning, helped us understand how gene networks can determine the development of a body and how they can sometimes . Gene networks are a set of genes, or parts of genes, that interact with each other to control a specific cell function. In 1995, three scientists won the Nobel prize for their contribution to this new understanding.

Fruit flies and humans have surprisingly similar biology. Andreas Prokop, Author provided

A startling likeness

Eventually, it emerged that the entire genomes of flies and humans showed astonishing similarities, and mechanisms or processes discovered in flies often turned out to apply to . Many human genes can even when inserted into the fly genome.

The common ancestor that founded the evolutionary lines of flies and humans, half a billion years ago, appears to have been equipped with biology so well-designed that many of its aspects are still maintained, such as mechanisms of growth or neuronal function. Because we are , many aspects of human biology and disease have been explored first in Drosophila. Meanwhile, is fast, cost-effective and extremely versatile. It’s ideal for .

Once knowledge has been gained in a fly, that knowledge can . Today, over 10,000 researchers worldwide are in many areas of science that relate to human biology and disease. It is used by for studying learning, memory, sleep, aggression, addiction and neural disorders. Not to mention cancer and ageing, processes of development, the gut microbiome, stem cells, muscles and the heart.

That said, flies are not mini-humans. They cannot be used to study personality loss seen in Alzheimer’s disease, for example. But they can be used to study why and bridge important gaps in our understanding of this type of disease.

Fruit flies hovering in your kitchen might be aggravating, but hopefully you will see them in a different light now.

, Professor of Cellular and Developmental Neurobiology,

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Centuries after the first golden coffins were taken to Europe, ancient Egyptian mummies still vividly capture people’s imaginations. Perhaps we’re awed by the grandeur of their rituals and tradition. But new discoveries keep challenging scientists’ perception of these ancient rites.

As a biomedical Egyptologist, I study mummies to learn about life in ancient populations. Over the last 10 years, I have seen a big change in our understanding of how, why and when mummies were created. This has mostly been driven by new scientific discoveries. Here are five of the most important ones that have changed what we know about this ancient process.

1. Mummification is older than archaeologists imagined

For decades, the oldest known mummies came from the Old Kingdom era (c.2500-2100BC) around the time Egyptians started using coffins more. These mummies are rare, but they show signs of being specially prepared by embalmers. Mummies from before the Old Kingdom period were thought to have been created naturally by burying bodies in graves cut into the hot, dry sand. Scientists thought embalming was developed to keep bodies preserved inside coffins.

But chemical tests published in and showed that resins and perfumes were already being used to help preserve the skin of the dead over 6,000 years ago, before coffins were common and long before the Old Kingdom era.

2. The ‘recipe’ varied across Egypt

Recent scientific studies of mummies and revealed how methods differed from place to place and weren’t standardised, as previously thought.

Each region had its own where mummies were produced in a complicated and closely guarded ritual. This secrecy means very few records survived.

Embalmers living in politically important areas such as (modern-day Luxor) had access to the latest mummification materials, as part of an extensive trade network. In more remote areas such as oases, embalmers had to make do. , used to dry the body, was heavy and difficult to transport. Resins and perfumes could be expensive as they were in exchange for other luxury goods.

Instead, the embalmers in these remote areas developed . For instance, they used sticks to make mummy bundles more rigid or to attach body parts that fell off during mummification. They also created composite mummies, made up of the parts of several people.

We don’t fully understand how experimentation in mummification emerged in different areas or time periods. There was probably an element of trial and error though.

3. Ancient accounts were not always reliable

The information we have about mummification comes mostly from two ancient Greek writers, and . They describe the steps of mummification such as using a hook to remove the brain through the nose. They also tell us the heart was left in the body because it was thought to be important for the afterlife.

using CT scanning have now shown the rules of mummification were less rigid than Herodotus and Diodorus Siculus thought. Only around a quarter of known mummies have their heart left in the body. And many mummies . If the embalmers did take the brain out, they sometimes used to avoid damaging the face. Holes have been found in the bottom of the skull and through different routes into the nose.

Not everyone could afford new linens or coffins for their dead loved one.

4. Egyptians upcycled coffins

In ancient Egypt, wood for coffins was scarce and . Not everyone could afford a new coffin or linen wrappings. A good coffin – but not a luxurious one – in the New Kingdom would or 250 loaves of bread.

Upcycling and recycling are not modern concepts. To save money, embalmers would often already in use. These could be repainted to include the name of the new owner or the parts were sometimes used to fashion a new coffin. Tombs were often raided by robbers looking for valuables, and afterwards they were often left open. This made it easy for others to search the tomb for coffins and wrappings to reuse.

Household linens were also often used as mummy wrappings once they outlived their usefulness. Modern research techniques such as are showing this practice was widespread. Coffin materials, linen wrappings and other materials are sometimes dated than the person they were buried with.

5. The tourist trade scrambled history

We now know mummies in museums outside of Egypt are . Many mummies are given a historical date based on their coffin style and decoration. The shape, decoration and religious texts on them changed over time.

But in the 19th and early 20th centuries, mummies were sold to tourists, scientists or collectors. Sellers put well-wrapped mummies into coffins from different tombs to encourage people to buy them. The mismatch only comes to light when a mummy is .

It is now illegal to take mummies or any other ancient artefact from Egypt. There are still a lot of mummies left in private houses though, bought more than a century ago and sometimes forgotten about.

Instead of one unwavering tradition, Egyptian mummification was variable. The funerary rituals available to someone demonstrated how important they and their family were. Being mummified using the most up-to-date techniques and materials not only helped secured a person’s position in the afterlife, it was an important sign of status.

It is impossible to know what the next archaeological or scientific find will show us. But one thing is clear: even ancient embalmers had to improvise sometimes.

, Lecturer in Biomedical Egyptology,

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Sometimes these infections can be very serious. The UK has seen a huge surge in hospital admissions during winter, putting the health service .

This had led some to question whether COVID damages our immune systems, leaving those who have been infected more vulnerable to other infectious diseases like the flu.

Another idea put forward to explain the surge in respiratory viruses is that children “missed out” on common childhood infections during the height of the pandemic, and that this has left them more vulnerable to these infections now owing to an “immunity debt”. But how credible are these explanations?

COVID and our immune systems

The human immune system has evolved to deal with a host of different infections. It has a variety of weapons it can deploy which work together not only to eradicate infectious agents, but also to remember them for a more rapid and tailored response upon any subsequent encounter.

Likewise, many infectious agents have developed tricks to try to evade our immune system. For example, a parasite called disguises itself to avoid the immune system detecting it.

SARS-CoV-2, the virus that causes COVID-19, similarly has tricks up its sleeve. Like many other viruses, it’s been shown to , particularly . Recent studies showed it can interfere with immune cells’ ability to detect it . This is concerning, but it’s not clear that such changes impact immunity to other infections.

Short-lived changes in a person’s immune defences are normal when they’ve been exposed to an infection. Several studies have now shown that, in response to SARS-CoV-2, specialised white blood cells called lymphocytes grow in number. These lymphocytes also display changes in their features typical of cell , such as changes in .

Such changes may sound dramatic to the non-expert if taken out of context (called “ascertainment bias”). But they’re normal and merely indicate that the immune system is working as it should. Research has confirmed that, for most people, the immune system following recovery.

Some exceptions

SARS-CoV-2, like many viruses, doesn’t affect everyone equally. We’ve known for some time that certain groups, including older people and those with underlying health complications such as , can be more susceptible to severe disease when they contract COVID.

This vulnerability is associated with an irregular immune response to SARS-CoV-2 that results in inflammation. Here we see, for instance, reduced numbers of lymphocytes and changes to known as .

Still, for most of these vulnerable people, the immune system over the next two to four months. However, a small subset of patients, particularly those who had severe COVID or have underlying medical issues, retain beyond six months after infection.

The significance of these findings isn’t clear, and longer-term studies considering the impact of underlying health conditions on immune function will be needed. But for most people, there’s no evidence to suggest immune damage following a COVID infection.

For some people with underlying health conditions, immune changes appear to last longer.

What about long COVID?

Emerging the most differences in immune cells after a COVID infection occur in people who have developed .

So far, no data points to immune deficiency in long COVID patients. But an overactive immune response can actually cause harm, and the immune cell changes seen in long COVID patients seem consistent with a vigorous immune response. This may explain the variety of post-infection consequences and symptoms that people with face.

Immunity debt

The “immunity debt” hypothesis suggests the immune system is like a muscle requiring near-constant exposure to infectious agents to keep it functioning. So, the argument goes, a lack of exposure due to lockdowns damaged immune development, especially in children, by making our immune systems “forget” earlier knowledge. This supposedly left them more vulnerable to infections when social mixing returned to normal.

Though this idea has gained traction, there’s no immunological evidence to support it. It’s not true to say we require a constant background of infection for our immune system to work. Our immune systems are immensely robust and powerful. For example, immune memory to the 1918 influenza pandemic was still evident .

It’s also not strictly true to say children weren’t exposed to viruses during the early pandemic. Lockdowns didn’t commence until after waves of the usual winter respiratory infections in 2019/2020, and schools in the UK reopened in autumn 2020 with variable preventive measures, so children were still exposed to infections, including COVID-19.

The cold-causing viruses didn’t completely vanish by any means. For example, there was a significant in the UK in 2021.

Nonetheless, lockdowns and other protective measures probably did reduce exposure to viruses, and for some children this shifted when and at what age they were first exposed to viruses such as RSV. This, taken alongside a high background of COVID, and relatively poor COVID and flu vaccine uptake, could all be making particularly bad. However, a change in the timing of when people are exposed leading to a surge of infections doesn’t necessarily mean that individual immunity has been damaged.

Our knowledge of the immune response to COVID is rapidly expanding. The most consistent findings show are protecting us from the very worst effects of SARS-CoV-2 and that, post-vaccination, our immune system is working exactly as it should.

However, findings of altered immune signatures in some recovered patients and those with long COVID require further investigation.

, Professor in Biomedical Sciences,

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In this study, “unsafe listening” relates to not only how loud the noise is, but for how long a person is exposed. A person’s maximum recommended noise exposure dose is no more than 85 dB (decibels) for eight hours a day. This is roughly as loud as city traffic or a busy restaurant.

For every three decibel increase in noise, this equates to a doubling in sound energy – meaning that the exposure time should be halved (known as the “”). So if the sound in a typical concert is around 105 dB, a person would exceed their daily noise dose within approximately five minutes of being there. Headphones and earphones can reach similar levels when put up to maximum volume.

Frequently engaging in unsafe listening practices can lead to permanent hearing loss. Fortunately, there are many easy things you can do to lower this risk.

Knowing your risk

It’s important to note this study only estimates the number of young people who could be at risk of hearing loss – it does not report on how many people have already developed hearing loss due to unsafe listening practices. The authors acknowledge that more well-designed studies are needed to better understand the effects of recreational noise exposure across the lifespan.

However, we do know from studies on other types of noise just how harmful it can be to hearing. For example, studies investigating the effects of (such as from loud construction machinery) have shown that it’s linked with high levels of hearing loss and tinnitus (a ringing or buzzing sensation in the ears). In such jobs, average daily noise exposures can exceed 100 dB. Similar problems have also been found in the music industry, with approximately .

In theory, the delicate parts of the inner ear are equally as susceptible to damage from loud music as they are from noisy machinery and power tools. Regular exposure to high levels of noise can destroy the sensory hair cells in the ear that are responsible for amplifying everyday sounds. , meaning that noise-induced hearing loss is permanent.

Early symptoms of hearing damage can include muffled hearing (like having wool in your ears) and tinnitus – both of which can be common after exposure to loud noise. But even though these symptoms may disappear within a couple of hours or days, it has been suggested that these symptoms could still be of more insidious damage to parts of the inner ear.

While these early signs of hearing loss might be nothing more than a minor annoyance when you’re young, as hearing loss worsens it can have a major impact on quality of life. Some studies have even shown it’s associated with later in life. This is why it’s vital to look after your hearing even when you’re young.

Protecting your hearing

The first and most effective way to reduce the risk of hearing loss is to eliminate the noise at its source. In other words, turn the volume down. This is easy to do with personal listening devices, since many smartphones are already wired to alert you when you’ve been listening for too long at a high volume.

But turning the volume down can be harder to do when attending loud events. To protect yourself, limit your exposure – either by moving away from the sound source (avoid standing in front of loudspeakers) or in a quiet space every 15 minutes or so. It’s also recommended you give your ears if you spend around two hours in a 100 dB environment, such as a club or concert.

You could also use hearing protection devices (such as earplugs) at noisy events. These are usually considered as a last line of defence, but may be the best option if you are unable to limit your exposure – or don’t want to.

Disposable foam earplugs will help to prevent noise-induced hearing loss if . But they aren’t really designed for listening to music and can make music sound muffled, which puts many people off using them. Musicians’ earplugs are a better solution, as these are designed to evenly balance noise reduction across all frequencies, which preserves the quality of the music.

Even if you follow these measures to protect your hearing, it’s still advisable to get your hearing checked by an audiologist. While there’s no rule on how regularly you should get your hearing checked when you’re young, some audiologists recommend having at least to serve as a baseline, and then to get retested approximately every five years to monitor any changes.

But if you’re regularly exposed to noise or already have some hearing loss, it’s advised you get your hearing checked more frequently. You should also if you notice any sudden changes in your hearing.

, Research Associate, Hearing Science,

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The primary remedy is the simple hearing aid. It is an essential helpmate to ensure continued social contact and quality of life. Simple, but not necessarily cheap. They cost around US$1,000 (£850) per ear for a reasonable quality device – not an insubstantial amount, especially in times of austerity. Although, in the UK they are free on the NHS.

The basic function of a hearing aid is to amplify sound in a pattern to match the profile of the loss of hearing sensitivity in the wearer. Legally, a hearing aid can only be dispensed by a registered clinician. But a new class of devices, called personal sound amplification products (PSAPs), bypass this legal restriction.

A PSAP is not a difficult device to build. Most of us already carry the core components around in our pockets in the form of a smartphone. A microphone, some computer processing and either a loudspeaker or earpiece are “all” that you need.

The processing, in the form of apps, has been available for many years. In its simplest form, even the ability to separately control the treble and bass of your smartphone performs like a PSAP.

Taking this further, a from researchers in Taiwan reports on the possible use of earbuds as PSAPs, specifically Apple AirPods, incorporating the Apple “Live Listen” function. Live Listen allows the microphone on an iPhone to amplify audio and transmit it wirelessly to AirPods.

Using technical measures, a few of these models meet some of the for PSAPs. In the paper, volunteers with hearing impairment were assessed on their ability to repeat back speech presented in either quiet or in noise. The researchers reported similar improvements in performance to those available from either a premium or a basic hearing aid when compared with unaided hearing.

Does this mean that the extensive development work put into hearing aids over the past 100 years has been usurped? Not really.

Hearing aids aren’t cheap.

The most common form of hearing loss that can’t be fixed with surgery is the loss in the cellular mechanisms of the cochlea – the tiny snail-shaped organ that sits at the end of the ear canal. This loss is not like blocking your ears. A person loses the sensitivity to soft sounds, but loud sounds often appear just as loud as to a person with unimpaired hearing.

The solution is an automatic volume control: turning up quiet sounds and turning down too-loud sounds. This automatic control can be performed in a smartphone app so that the user always has a comfortable listening experience. Since hearing loss also varies with audio frequency, the behaviour of the automatic volume controls has to change with frequency.

A modern hearing aid performs multiple channels of automatic volume control but has a host of other features operating at the same time. For example, reducing interfering noises, preventing squealing and operating “directional microphones” to focus on the desired sound source. All of these features contribute to the long-term wearability of any hearing aid. This latest study is light on detail as to what processing was performed in the AirPods other than the use of volume control.

Not a long-term fix

So why are hearing aids more expensive than PSAPs? When an audiologist measures hearing loss, they also look to identify the causes of the loss – which can be many more than just the changes expected with old age. Some of these causes can be very serious and require treatment. This necessary human expertise has to be paid for.

There are also serious consequences of untreated or under-treated hearing loss. Uncorrected losses of our senses are associated with longer-term declines in mental abilities, with an . These declines are , or even decades, and are associated with massive costs – costs that will need to be covered by families and healthcare systems.

The researchers in the new study say that PSAPs “could potentially bridge the gap between persons with hearing difficulties and their first step to seeking hearing assistance”. But it would be unwise to see them as a long-term fix.

, Senior Research Fellow, Division of Human Communication, Development and Hearing,

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When I was about seven or eight, I asserted that I wanted to be a scientist, or so my parents told me years later, even though I would have had little idea of what that word meant. In my mind, I was perhaps associating it with making momentous discoveries that were immediately recognised and applauded by the whole world. Soon after, I avidly read , the book by Eve Curie about her mother Marie and how she overcame poverty and the many challenges faced by women in the late 19th and early 20th century to become a Nobel prize-winning scientist. Marie Curie became my lodestar for the future and thanks to my parents’ support and self-sacrifice, I did eventually become a scientist.

Marie Curie won two Nobel Prizes in 1903 for Physics and in 1911 for Chemistry.

Many years later, I found myself confronting what seemed like insuperable odds just as Curie did, though in very different circumstances. I have been an independent researcher since the age of 26 when I completed my PhD. My subsequent research in a Cambridge University department on (a complex of DNA and proteins) went well. Then, after eight years, my husband and I moved to Swagֱ�� where the head of the institute where I worked for 12 years decided to end my contract, leaving me jobless and lab-less.

In the decades that followed, my research into viruses as a possible cause of Alzheimer’s disease was greeted with much hostility, and almost all my funding applications were refused: a hostility that has continued for 25 years and which has only recently abated, thanks to .

I, along with my tiny research group, survived only through the award of a few small grants from more open-minded charities and companies interested in new approaches. Once I even managed to swap a business class ticket to the US (that was provided for me to speak at a conference) for economy class, so I could use the several thousand-dollar surplus for my lab instead.

But, after years of struggle, there is finally hope for this line of research. An for Alzheimer’s – the first ever – is now taking place at Columbia University. This study is building on the years of work done by my team. Meanwhile, our is looking into the way infectious illnesses increase the risk of Alzheimer’s.

Dementia brought home

Career and academic challenges can always be balanced with the help of a support network: a family. I was always lucky with mine. During many of these years, my husband, Shaul Itzhaki, a retired academic who had worked on nucleic acid biochemistry, supported my struggles and never once suggested that I change to a safer, more conventional and non-contentious topic. He was always touchingly happy with any successes I had, and I will always remember our celebratory days when I was awarded a for Medical Research, and later a Newnham College Fellowship, during our years in Cambridge.

Sadly, he died in April 2022, after suffering for about ten years from vascular dementia (a dementia distinct from Alzheimer’s disease but with many similar symptoms) and latterly, from a fractured femur that disabled him. The last four or so years were particularly hard to endure as he became increasingly aware of his failing memory. The term “brain fog” is often used in this context, but to me, it seemed more like a mist through which he could very dimly see or perceive what he was struggling to recall; the frustration – desperation, perhaps – that he felt at his inability to grasp, hold, then voice these elusive thoughts was pitiful.

The author in her laboratory. Author provided

I often took him to talks on topics such as the climate, migration, history and ageing, hoping to keep his mind occupied. He seemed to understand many of them, but afterwards, he was quite unable to discuss them, as his memory and ability to speak were declining inexorably. Communication of any type between us was slowly becoming impossible, although he was the person with whom I had once shared my thoughts and hopes, just as he had done with me, and it became particularly sad and unsettling, as we had had so many interests in common. Eventually came the realisation that I had “lost” him. It was a bereavement – the loss of him as a person, loss of a mind, not the death of a body; he was existing but not really living.

Another common feature of dementia – sudden changes of mood – affected him during these years. He had been a generally gentle, courteous person. But when, at times, the illness overcame his natural traits, he became violently angry, often for no obvious reason. Part of the problem was that his sense of location had faltered and often during the evenings he became convinced that we were about to leave and go “home” to Swagֱ��, a place we had left in 2013. He would ask repeatedly and anxiously when we had to leave to catch the train to get there. Television programmes, even those on historical events, which would have been of particular interest to him, had to be vetted as he lost himself within them. So that after watching one that dealt with, say, the horrors of war, he thought that he was actually living in that frightening world.

Of course, there are so many families going through what my family went through. And there will be many more. That fact has provided one of the main motives for my pursuing my research, despite all the difficulties that have come with it.

Early challenges

During the last five years, studies supporting the idea of a viral role in Alzheimer’s disease have . Despite this, there is still much opposition to the concept, while many in the field still ignore it.

I am often asked why there has been such hostility. A charitable explanation is that the possible role of a virus in dementia is difficult for others to assess because it straddles two very different topics: virology and Alzheimer’s disease. Also, many cannot grasp the concept that people can be infected but not affected (asymptomatic, when the virus resides in the brain without causing symptoms) so they dismiss the data. Either way, I have always stressed that many possible factors lead to Alzheimer’s disease – a viral role is just one of them.

My interest in this particular area began, rather unpromisingly, in 1978 when the aforementioned head of institute ended my work contract. The reason he cited was that my research on chromatin, and on the effects of carcinogens on chromatin, was “rather individualistic”. I thought this was an extraordinarily inept criticism, as I had generally been acknowledged as being an innovative researcher, and innovation is surely the key to good research. The funding body offered me a post in Glasgow, but that would have meant leaving my husband and children in Swagֱ��.

Luckily, I was immediately given a home in the lab of a medical virologist friend, Richard Sutton. Sutton was an eccentric and pioneering man. He was dogged and wiley, in an endearing way. It was Sutton who first suggested to me the possibility of viral involvement in Alzheimer’s disease.

The argument for the role of the cold sore virus, herpes simplex type 1 (HSV1), in Alzheimer’s disease was first suggested by American neuropathologist in 1984. But he did not pursue the idea in any practical way. Sutton and I carried out what was probably the first convincing experiment seeking the DNA of HSV1 in the human brain. We had predicted that it might be detectable in the brain of immunosuppressed patients because in the absence of an adequate immune system to keep it under control, the virus would be able to multiply. We did indeed find it, and published our in 1986.

The central concept

is mainly transmitted by oral-to-oral contact, causing oral herpes (cold sores). Globally, an estimated 3.7 billion people under age 50 (67%) have HSV1 infection. Most infections are asymptomatic.

Over the years, the supportive data we gathered for the key role of HSV1 in Alzheimer’s led me to propose a central concept: that HSV1 is a major cause of Alzheimer’s disease; that in many people, the virus travels to the brain, probably in middle age, and remains present there in latent (dormant) form, but is frequently activated by episodes of stress, head injury, immuno- suppression and infections. These “reactivations” lead to productive HSV1 infection and inflammation (and consequent damage to the brain) over the years. The accumulated damage leads eventually to the development of the disease.

The possible role of HSV1, specifically, was proposed for three main reasons. The locations of the damage the virus causes in the brain during the rare but extremely serious acute disease herpes simplex encephalitis (HSE) – caused by HSV1 – are precisely the main sites of damage found in the brains of patients with Alzheimer’s disease.

The other reasons for implicating HSV1 were that it is very common, affecting of the population (in earlier decades more probably 90%), and its ability to remain dormant in the body for years.

These features meet two main characteristics of Alzheimer’s disease: that it is all too common, and that it almost always waits until old age to strike its victims. Certain other infectious agents are probably involved too, perhaps individually or in combination, but so far these have been less well studied than HSV1.

The laboratory work

I was offered a more long-term prospect for my research in a department of the University of Swagֱ��’s Institute of Science and Technology. The head of the department, John Cronley Dillon, was a larger-than-life character, a bon viveur and art lover, full of novel ideas and wild enthusiasm. He encouraged me to build up a research group (minuscule though it was) and eventually we started the research on HSV1 and Alzheimer’s.

It was known that when a person is infected with HSV1, the virus resides lifelong in the peripheral nervous system (PNS) – the part of the nervous system that doesn’t include the brain and the spinal cord — in a latent state. It is dormant until it is activated by events such as stress. In 1989 we decided to look for HSV1 in the brain, using the technique of polymerase chain reaction, or PCR. We used to examine DNA extracted from autopsy specimens of Alzheimer’s disease patients.

This was the first time PCR, then a new technique, had been used for this purpose. The principle of PCR is to detect a specific sequence in the target DNA by chemically amplifying it, thereby making it vastly more sensitive than the methods used in the previous few studies seeking HSV1 DNA in the brain. However, this method was prone to contamination and could produce spurious data. This meant that my poor PhD student, Gordon Jamieson, spent many frustrating months trying to get it to work satisfactorily. So we were overjoyed when , unambiguously, the DNA of the virus in the brain in 1991.

This was the first microbe to be detected in the human brain (in controls, in the absence of a disease). We were puzzled, though, as to why the virus was present in a high proportion of brains – both control brain specimens (people who had not been diagnosed with Alzheimer’s) as well as the brains of patients who had died with the disease. This near equality of prevalence does not undermine the role of HSV1 in Alzheimer’s, as some in the field have asserted. Many of the control brains were, in fact, infected with HSV1 but were asymptomatic.

So people can be infected but be asymptomatic, indicating that infection alone is not sufficient to cause disease. A very relevant example is that of cold sores which afflict only a proportion (ranging from 20-40%) of those infected with HSV1. The other 60-80% are asymptomatic. Clearly, another factor determines the degree of damage caused by the virus.

Other supporting factors

That was something we identified in 1997 when that the virus confers a high risk of Alzheimer’s disease when in the brains of people who carry a specific genetic factor. We were extremely excited by this finding, but also apprehensive about adverse reactions of some in the field, as had occurred before when we discovered HSV1 DNA in elderly brains.

So we were even more excited when, after I’d suggested examining cold sore sufferers (via a small blood sample), to find what variant of the specific genetic factor they carried, we discovered that it was the same variant as for Alzheimer’s. In other words, the same variant of the genetic factor conferred a risk of damage in the peripheral nervous system, as well as the central nervous system.

Of course, the question arose as to what it is doing, if anything, in the brain. Is it residing there merely as a passenger, doing little or nothing, or does it cause damage?

We by examining cerebrospinal fluid (the liquid that bathes the brain) looking for antibodies to the virus. We detected these antibodies in most samples of cerebrospinal fluid, again, consistently, in both Alzheimer’s patients and those in the age-matched control groups. This showed that indeed the virus was not just a passive fellow traveller.

We then decided to find if there were direct links between the effects of HSV1 infection and Alzheimer’s. Very hesitantly, like explorers in a new continent, we infected human brain cells with HSV1, then stained the cells with antibodies to the specific abnormal proteins seen in Alzheimer’s brains – and .

To our surprise and delight we saw accumulations of both types of protein. Also, we found amyloid deposition in the brains of infected mice. However, getting the results published was a Sisyphean task and journal reviewers’ comments were often incredulous.

We subsequently used a very complex technique (in-situ PCR) which revealed that in tissue sections of brain, most of the viral DNA was located very specifically within amyloid plaques. This suggested that amyloid might act to cage the virus, thereby inactivating it. All this work provided strong support for a major role of HSV1 in Alzheimer’s, and much has since been extended by .

that anti-herpes treatment was protective because it substantially reduced the damage level in the cell cultures we were testing. This further supported a role for the virus in the disease – and pointed to a potential treatment.

A heretic shunned

But a viral role in the development of Alzheimer’s was still seen as heretical by many researchers, so our papers continued to be rejected by one journal after another.

For academics, having research published in top journals is often central to keeping your job and career progression because of the perceived value to universities (related to university league table rankings, supposed research quality and performance management).

Similarly, almost all of our grant applications over that 25 years were refused, too, which was even more serious as without funding, the people in my lab couldn’t be paid nor materials bought. I was very fortunate in having three successive post-doctoral researchers, Woan-Ru Lin, Curtis Dobson, and especially Matthew Wozniak, who were so dedicated that they were willing to continue to work even when on repeated short-term contracts (sometimes for less than 12 months).

So most of my time was taken up in writing research proposals and filling in application forms, interspersed with writing and submitting articles to journals, and when rejected, trying another. I had to face derision and hostile rants unaccompanied by any meaningful, scientific criticism from reviewers. A typical example was: “This grant essentially centres on a question of belief; are viruses important in Alzheimer’s disease, in my view they are not.”

Each rejection seemed like the end of the world. It was a heart-stopping moment when opening the envelope or email from the funding body and scanning the lines in the hope of finding the words, “I’m pleased to tell you …” – though all too often, I found the words, “I regret to tell you”. I hid, weeping tears of despair, while a part of my brain questioned whether the work really was nonsensical and whether the ideas were just wild fantasies.

At conferences, I was often shunned by prominent people in the field. My poster presentations were too (posters were the poor man’s alternative to giving a talk, a privilege I was rarely given). Although, hearteningly, I found that younger people were interested and excited by the research.

Later, I benefited from the generosity of a colleague, . Kulikowski was another eccentric who lived an upside-down life, working at night and either sleeping during the day or else amusing himself by lobbing provocative remarks at colleagues. He was really interested in our research, despite working in the totally different field of vision research.

I do realise of course that many others have suffered refusals of grant applications, and I understand how especially heartbreaking it is for those at the start of their career, as it usually means the end of all their hopes and dreams of becoming a scientist. I realise too that I had been exceptionally lucky in being able to do such utterly engrossing work – a continuous, totally fascinating puzzle and challenge – and in having a loving family.

But after each rejection my fear that the work would end was overwhelming. When I did get a grant – any grant – I was elated: the world sparkled. I was so happy and exuberant, not just with the funding but with the fact that some people in the field were supportive of, or at least willing to consider, a possible role for HSV1. I felt so encouraged, vindicated and ready to face any challenge in my work or from fellow scientists, and brimming over with ideas for new approaches.

Quite often in the later years, some strongly supported our central concept. But there was a huge divide between them and its opponents. And the hostility continues to this day. In 2019, an application by a colleague to a US funding body for a clinical trial of an antiviral for Alzheimer’s was refused. I was involved as an adviser because it was based on my lab’s research, though I was not an applicant.

One reviewer said: “This application is peripherally related to the idea that Human Herpes Virus (HHV) infection could play a role in Alzheimer’s disease pathogenesis … the evidence is weak, the supporting data are weak.” The second reviewer proclaimed: “The novelty of this approach appears to be quite lacking. The suggestion of latent microbe-based activation by (unknown) factors coincident with a ‘deteriorating immune system’ as the cause for Alzheimer’s seems like hand waving”: poetic perhaps, but hardly a brilliant display of scientific disputation. In fact, no adverse comments had ever been supported by any scientific argument, despite a public assertion once by a senior government official that the HSV1/Alzheimer’s work had been refuted (though when challenged, he was unable to cite any such article).

Most researchers acknowledge that new, surprising and challenging ideas should be viewed with caution. But ideas should not be dismissed without any deliberation. Perhaps another major reason for the hostility is that many people in the field have been working for several decades on amyloid as a cause, and so are understandably distressed on learning that it might not be a direct cause, except in rare familial cases. This occurs despite our repeatedly stressing that numerous factors contribute to Alzheimer’s and amyloid is clearly an important feature.

Exciting developments

But, as the Columbia University study shows, attitudes to the topic of Alzheimer’s and HSV1 are slowly, but steadily, improving. Of course, I am very happy about this, for the sake of patients and their carers. And I have to admit that recognition of the work on HSV1 is personally gratifying as, like most people, I am heartened to know that my work has achieved something.

I am pleased that the research that I and others are carrying out is now moving forwards in even more exciting directions, including the use of a 3D bioengineered human which, when infected with HSV1, displays many Alzheimer’s-like characteristics.

We are now investigating the effects of and a possible role for vaccinations. This follows an explanation I with my then-senior post-doctoral associate, Curtis Dobson, to account for that certain vaccines decreased the risk of Alzheimer’s disease. We suggested that infections might reactivate latent HSV1 in the brain and that vaccines might decrease the consequent risk of Alzheimer’s disease by reducing the occurrence of such infectious diseases.

For example, in the case of shingles – which is caused by another type of herpes virus, varicella zoster virus (VZV) – I carried out with Swagֱ�� University epidemiologists showed that vaccination against the disease may protect against the development of Alzheimer’s. Two subsequent studies showed the same result. However, much further work needs to be done to elucidate the findings that certain types of vaccine appear to reduce the risk of Alzheimer’s.

Scraping of a skin lesion showing characteristic giant cells in a patient with chicken pox (Varicella Zoster Virus), a type of herpes.

I, along with researchers at Tufts University, then if VZV (which also causes chickenpox) plays a role similar to HSV1 in causing brain damage leading to the development of Alzheimer’s.

showed that VZV infection of the cells does not lead to the formation of the main characteristic Alzheimer’s features in the brain. However, VZV infection does result in certain other Alzheimer’s-like features, including increased inflammation. And – importantly – VZV was seen to reactivate the latent HSV1 infection in the brain model, with the consequent occurrence of Alzheimer’s-like characteristics. This is consistent with our suggestion that infections reactivate latent HSV1 in the brain.

The that another herpes virus, Epstein Barr, is a cause of another brain disease (multiple sclerosis) strengthens the likelihood of viral involvement in certain other such diseases.

We now plan to find out if other infections cause HSV1 reactivation from latency. If they do, the obvious corollary would be to try to limit infections by vaccination, and by improving standards of hygiene and living conditions – a particular need in developing countries – to reduce microbial transmission.

In addition, we now have some exciting preliminary findings suggesting that percussive brain injury (for example, concussion) can cause HSV1 reactivation. This is a very different type of injury from infection and the results suggest that the virus might be pivotal in the brain’s response to diverse types of damage.

This is an exciting field of study and I hope bright young scientists will enter it. Nobody said being a scientist was easy, but with the right encouragement from family, friends and open-minded peers, it is amazing what challenges can be overcome.

, Professor Emeritus of Molecular Neurobiology at the University of Swagֱ�� and a Visiting Professorial Fellow,

This article is republished from under a Creative Commons license. Read the . For you: more from our :

As the pandemic continues, many countries are rolling out COVID booster vaccines. In the UK, the is offering a fourth dose to those at higher risk from a COVID infection, including people with certain underlying medical conditions, and those aged over 50.

The autumn booster shots are , meaning they target the original strain of SARS-CoV-2 (the virus that causes COVID-19) alongside the omicron variant.

These vaccines are effective at topping up and broadening . But we expect that, as we’ve seen with the original COVID shots, the protection they provide, particularly against becoming infected, in the months afterwards.

So we need to consider a vaccine strategy that will provide longer-term immunity. A new kid on the block – – could offer promise on this front.

Mucosal vaccines are delivered in your nose or throat, as sniffable or inhalable formulations. They may sound new but actually we’ve been using them for years to vaccinate against .

While conventional needle-in-your-arm vaccines induce a more systemic immune response, mucosal vaccines do something different. Viruses such as SARS-CoV-2 enter our systems via our nose and mouth when we breathe in small virus-containing droplets. This means immunity in our nose, mouth and throat really matters to stop infections.

Mucosal vaccines are designed to target this “”. The mucosal immune system has the potential to stop the virus in its tracks when it enters the body, so scientists predict that mucosal vaccines could prevent infection.

Mucosal immunity may also be better at getting our immune system to remember SARS-CoV-2. Memory cells are specialised long-lived immune cells that remember the virus and carry instructions for our immune cells to be quickly deployed if it attacks again. Systemic vaccines are not so good at activating the memory cells in our nose and throat, but .

Meanwhile, the fact that mucosal vaccines work locally could mean a . This, coupled with less stringent storage requirements compared with some conventional vaccines, may mean mucosal vaccines could be deployed more efficiently in resource-poor countries and be an important tool for .

Mucosal vaccines would probably also be a lot more appealing to those with needle phobias. Roughly admit to being afraid of needles, with the highest rates of phobia seen in youth, black and Asian groups – groups we know have and more vaccine hesitancy.

Mucosal vaccines could make a big difference for people with needle phobias.

The advantages are clear – but what does the evidence say?

Several mucosal vaccine candidates are being explored in . Results just published on a nasal booster vaccine in mice showed that were induced in the nasal and upper respiratory tracts.

Similarly encouraging results have been reported in and . Several trials to see if these results can be replicated in humans.

Iran, Russia, India and China have already introduced mucosal vaccines despite published data on their candidate vaccines . But some data has been publicly released.

Results from phase II human trials of an inhalable vaccine, now being rolled out in , were released as (a study yet to be peer-reviewed). While the study didn’t assess mucosal responses, it did show that systemic antibody levels were higher and remained higher over the six months assessed compared with a conventional booster.

But the picture is mixed. A of a nasal formulation of the Oxford AstraZeneca vaccine showed little to no induction of mucosal immunity and weaker systemic antibody responses compared with a conventional vaccine.

The reasons for these disparities are not clear, but they could include the method of delivery. The administration of mucosal vaccines requires precise engineering and to ensure the small droplets containing the vaccine are easily inhaled.

Several strategies have been used to deliver mucosal vaccines including nebulisers (a machine that turns liquids into a fine mist that can be inhaled), nasal sprays and inhalable devices like the inhalers asthmatics commonly use.

The particle size, formulation (the ingredients and how they’re combined), as well as the vaccine’s ability to stick to and enter our cells will all affect how effectively the vaccine particles are taken up in the body. This is called the vaccine’s “bioavailablity”. We still have a lot to learn about which delivery strategy is optimal for which vaccine.

So where does this leave us?

This pandemic is still very much ongoing. And we’re learning more all the time about the long-term implications of COVID infections on our health, including and long COVID.

This, coupled with the emergence of ever-more persistent , mean it’s important to keep protecting ourselves and our loved ones from the worst effects of the disease. Vaccines are some of the best weapons we have.

It will be important to watch and learn from the mucosal vaccine rollout in other countries and scrutinise their data when it’s released.

Meanwhile, given the urgent need for long-term vaccines, it would seem prudent to invest in strategies, not just for the development but also the manufacture of such vaccines. They could be an invaluable tool in this pandemic, but also against many other infections, including those we have yet to encounter.

, Professor in Biomedical Sciences,

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The World Health Organization declared COVID a pandemic on March 11 2020. In the two years since, countries have diverged on their containment strategies, introducing many different ways of mitigating the virus, to varying effect. Here, four health experts look at what has worked well, what mistakes scientists and policymakers made, and what needs to be done to protect human health from here on.

Andrew Lee, Professor of Public Health, University of Sheffield

Most governments didn’t get their pandemic responses right. The initial response decisive, rapid, transparently communicated and delivered at scale. Often it wasn’t.

Before the arrival of effective treatments or vaccines, blunt measures such as lockdowns were necessary to minimise loss of life. Indeed, in places like New Zealand, Taiwan and South Korea, where the spread of infection was initially low, lockdowns were effective and . Countries that successfully pursued elimination strategies experienced lower case numbers and deaths, buying time until vaccine protection arrived.

However, we’re now in a different phase of the pandemic. Vaccines have changed the risk considerably. Eliminating the virus also seems unachievable currently, with widespread transmission in virtually every country. The value of lockdowns and travel restrictions is now greatly diminished and their need factoring in.

To live safely with the virus, we must heed lessons from the last two years. These include moving away from , which drives people to go to work or school when ill, as well as appreciating the importance of and face masks in reducing the spread of airborne diseases. The threat of new variants hasn’t gone away, so of the virus will still be needed globally.

We need to learn from our mistakes too. Narrow, hospital-centric perspectives meant we didn’t protect vulnerable and disadvantaged people enough, such as care-home residents, people with , and the poor. We also didn’t appreciate soon enough that the pandemic was a – interacting with and amplifying many other diseases, such as mental ill health, smoking and alcohol-related illnesses.

Sheena Cruickshank, Professor in Biomedical Sciences, University of Swagֱ��

Immunological discoveries have been critical in the fight against COVID. By and large they wouldn’t have happened without the cooperation of scientists across disciplines and nations – nor without help from the public worldwide. Scientific collaboration has been one of the major successes of the pandemic.

Early access to the coronavirus’s genetic code, coupled with our knowledge of other members of the virus’s family (such as Mers and Sars), enabled work on vaccines to start quickly. Knowledge that the virus used its spike protein to enter our cells then gave us an initial target for vaccines.

Decades of experience in vaccine development, together with investment from governments and the pharmaceutical industry, as well as the participation of hundreds of thousands of volunteers in clinical trials, then enabled vaccine development to be fast-tracked to an astonishing degree. On vaccine development, the world got it right.

Understanding the immune response to COVID has helped us work out why some groups (such as the elderly) are much more vulnerable to . National studies have used their size and breadth to that correlate with protection or , which can improve patient outcomes and inform new treatments.

However, lives continue to be lost because of poor vaccine equity, with many countries still deprived of vaccines and drugs that could help them. Lives have also been lost due to disinformation – fuelling mistrust, vaccine hesitancy and advocacy of dangerous or inappropriate “treatments” for COVID. There’s still so much to be done to ensure good access to and uptake of vaccines worldwide.

KK Cheng, Professor of Public Health and Primary Care, University of Birmingham

Very few countries with strong public health traditions have avoided catastrophes in the pandemic. Why?

One explanation is that most developed countries were completely untouched by the 2003 Sars outbreak and were only affected mildly by the 2009 swine flu pandemic. Complacency crept in, and there was also general lack of experience in dealing with a pandemic.

Also, in early 2020, there were : first that the coronavirus, like the influenza virus, simply couldn’t be contained, even for a few months; and second that extreme restrictive measures, which we now call “lockdown”, would be unfeasible in liberal democracies. Both turned out to be untrue.

In the UK, the failure to appreciate the importance of early action, as if one was dealing with wildfires, also resulted in delays in introducing or tightening control measures for fear of adverse economic impacts. These high-level problems culminated in downstream disasters including inadequate testing capacity, lack of PPE in health and care settings, inappropriate infection control in care homes, dysfunctional test-and-trace systems and failure of home isolation of cases.

The potential benefits of island states were also in many cases squandered by loose border controls. Australia and New Zealand showed countries like the UK what was theoretically possible in containing the virus – at least in the pandemic’s earlier stages.

One ongoing global failure is the inequitable distribution of vaccines. Still of people in low-income countries have received at least one dose.

Trish Greenhalgh, Professor of Primary Care Health Sciences, University of Oxford

We initially assumed the pandemic would be solved by evidence-based medicine – a school of research dominated by the search for generalisable truths (“what is the effect size of intervention X on outcome Y in disease Z?”). While this approach helped find for COVID, it threw us way off the scent for evaluating non-pharmaceutical interventions such as masks.

While obsessing over the need for (“masks on” versus “masks off”), we suppressed our scientific imagination. We failed to wonder sufficiently at the novelty of COVID and the significance of its unique patterns of spread, such as , and the vastly higher chance of catching COVID . All these things should have raised hypotheses early on about a predominantly and the potential value of masks.

We also viewed masks too simplistically, failing to understand them as a in a complex system. Masks vary in and can be fitted . They protect other people as well as the wearer – hence, their effects at population level need to be rather than just tested in one-off experiments. Plus, masking (or refusing to mask) is a , tied to identity and values; many people refused to mask, and became, sadly, part of masking.

Two years ago, I was writing my first academic paper about COVID, arguing for using the and introducing public masking “just in case”. It was another four months – and 40,000 deaths – before the UK did.

, Professor of Public Health, ; , Professor of Public Health and Primary Care and Director of the Institute of Applied Health Research, ; , Professor in Biomedical Sciences, , and , Professor of Primary Care Health Sciences,

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Ageing isn’t just a change in how we feel or look, ageing happens at a cellular level. In a lab culture dish, adult skin cells divide roughly 50 times before stopping. But skin cells from a newborn baby can divide 80 or 90 times. And on the flip side, cells from someone elderly divide only around .

Ageing is also evident in our genes. Our genetic material is modified over time – chemicals can be attached that change which genes are switched on or off. These are called , and they build up as we age. Another kind of change takes place at the ends of our cell’s DNA. Repeating segments of DNA called telomeres act like the plastic tip of a shoelace, preventing the twisted coils of genetic material from fraying at the ends or knotting together. But these telomeres shorten each time a cell divides. We don’t know if short telomeres are merely a mark of ageing, like grey hair, or are part of the process by which cells age.

Cells, chromosomes and telomeres

To keep alive and keep dividing, immune cells stop their telomeres shortening when they multiply, . This is probably a contributing factor in their apparent immortality. Drugs that stop telomerase from working also show (although cancer cells can evolve resistance).

Bigger question

Given that ageing has such a profound effect on our cells and genes – the effects mentioned here being just some examples – a much bigger question emerges: why does this happen? Why do we age?

It was once thought that ageing happened for the continuing evolution of species. In other words, the evolution of a species requires a turnover of individuals. However, one problem with this idea is that most life on Earth doesn’t ever reach old age. Most animals are killed by predators, disease, the climate or starvation. So an inbuilt limit on an animal’s lifespan may not be important to evolution.

Another view is that ageing is simply a side-effect of the damage that builds up over time caused by metabolism or exposure to ultraviolet light from the Sun. We do know that genes are damaged as we age, but it is not proven that this drives ageing directly. Another possibility is that ageing might have evolved as a defence against cancer. Since cells accumulate genetic damage over time, they may have evolved a process to not persist in the body for too long, in case this damage eventually causes a cell to turn cancerous.

As we age, some of the body’s cells enter a state called senescence, in which a cell stays alive but stops dividing. Senescent cells accumulate in the body over a lifetime – especially in the skin, liver, lung and spleen – and have both beneficial and detrimental effects.

They are beneficial because they secrete chemicals that help repair damaged tissue, but over a long period of time, as senescent cells increase in number, they can disrupt the normal structure of organs and tissues. These cells could be an underlying cause of many of the problems we associate with ageing. Mice in which senescent cells were cleared were profoundly delayed in showing .

We can describe a lot of what happens during ageing at the level of what physically happens to our genes, cells and organs. But the fundamental question of why we age is still open. In all likelihood, there is more than one correct answer.

Of course, nobody knows whether Bezos’s company can succeed in helping extend the human lifespan. But what is clear is that by studying ageing, exciting new discoveries are bound to emerge. Never listen to anyone who says the big questions have already been answered. As I’ve recently detailed in a book about new technology and the human body, , I’m confident that dramatic breakthroughs will profoundly change the experience of being human in the coming century.

, Professor of Immunology,

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On Friday, January 7 2022, David Bennett became the world’s first person to successfully receive a . The eight-hour-long operation by surgeons at the University of Maryland Medical Center in Baltimore, USA, was no doubt arduous. But it was a short final step in a 60-year-long journey to genetically alter the pig’s heart so that it would not be immediately rejected – a journey that began with a plane crash in Oxford in the summer of 1940.

It was a hot Sunday afternoon when Peter Medawar, then 25, enjoying garden life in Oxford with his wife Jean and eldest daughter Caroline, was startled by the sight and noise of a bomber flying low towards them. The plane crashed violently in a garden 200m away. The pilot survived but suffered horrific burns. Medawar had trained as a zoologist, but his recent research had been to find out which antibiotics were best at treating burns. For the pilot who just crashed, doctors were at their wits’ end in deciding the right medication and asked Medawar to help.

The visceral shock of pacing the war wounds hospital spurred the young Medawar to think and work to a degree of intensity that he hadn’t known he was capable of. He saw airmen with much of their skin incinerated, lying in agony: while their lives could be prolonged by new medical advances – blood transfusions and antibiotics - there was no way of treating these horrific burns.

When doctors transplanted skin from one person to the next, it was destroyed soon after. At the time, doctors didn’t think there was any fundamental problem, only that the actual practicalities had to be perfected – the cutting and sewing. But Medawar thought something else was the problem. He obtained a grant from the War Wounds Committee and left home to surround himself with the problem, spending two months in a cheap hotel to work with Scottish surgeon Tom Gibson in the Burns Unit of the Glasgow Royal Infirmary. Together, they set out to observe exactly what happened during transplant rejection.

Their first patient was a 22-year-old woman, named in papers only as Mrs McK. She had been rushed to the Glasgow Royal Infirmary with deep burns down her right side from falling against her gas fire. To treat her, one area of her wound was covered with skin from her thigh and another area with skin taken from her brother’s thigh. A few days later, under a microscope, Mrs McK’s immune cells had invaded the skin grafts taken from her brother. Days later, the brother’s grafts degenerated. Her immune cells had caused the rejection.

Next, back in Oxford, Medawar chose to test this carefully using rabbits. Taking 25 rabbits, he grafted pieces of skin from each one onto every other one. If you’ve ever wondered what it might take to win a Nobel prize, Medawar’s starts here - with an important idea to be tested by 625 operations on 25 rabbits (25 x 25 individual skin grafts).

He showed that skin could not be grafted between different rabbits. Crucially, he also showed that in the second round of grafts, rejection happened more quickly the second time around, the hallmark of an immune reaction. The revolution starts here because Medawar and his team discovered that transplantation can work as long as an immune reaction is stopped. Medawar worked before genes and proteins could be easily manipulated, but this is relatively easy nowadays.

In the limelight again

Science of the immune system is in the limelight today because of the current pandemic. But as the science of immunity progresses, there are other big spin-offs, like new ways of switching off immune responses for avoiding transplant rejection.

In fact, as I’ve detailed in a book, , so many scientific and medical breakthroughs are happening, from new cancer therapies to manipulating the body’s genes or microbiome, I think we are at the cusp of a revolutionary time in virtually every aspect of human biology.

Medawar’s name endures not only his work on transplantation but also because of the brilliance of his writing. Richard Dawkins calls him the “wittiest scientist ever” and dedicated his 2021 collection of essays to him. The day before his first stroke in 1969, Medawar ended a lecture with a quotation from the 17th-century philosopher Thomas Hobbes proclaiming that life is like a race and the most important thing is to be in it, to be fully engaged, ambitious and go-getting, to improve the world. Eighteen years later, that same quotation was engraved on his : “There can be no contentment but in proceeding.”

, Professor of Immunology,

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But there’s a problem. COVID antibodies don’t – hence the desire for boosters. Indeed, while these extra jabs maintain against severe COVID, it’s estimated that people receiving a third dose of the Pfizer vaccine will see their protection against developing COVID symptoms (of any degree) 75% to 45% over the ten weeks following their booster. Scientists have whether topping up antibodies, only to see them soon fade away, is sustainable.

If we want to develop lasting immunity to COVID, it’s perhaps time to look again at our wider immune response. Antibodies are just one part of our intricate and intertwined immune system. Specifically, it’s maybe time we focused on T cells.

How different immune cells work

When the body is infected, say with a virus, it responds by producing white blood cells called lymphocytes. The are B cells, which make antibodies, and T cells, which either support B cell antibody production or act as killer cells to destroy the virus. Some T cells and B cells also become long-lasting memory cells that know what to do if they meet the same infection again.

B cells and T cells “see” the virus in different ways. Generally speaking, B cells recognise shapes on the outside of the virus, creating antibodies that will lock on to those (a bit like two jigsaw pieces that match). T cells instead recognise bits of the amino acids that build the virus, including bits that might normally be found inside it.

Every virus has lots of unique features, both inside and out. A person’s immune response can end up making a variety of T cells and B cells that between them target a whole range of these features. This is sometimes called “breadth of response”. A good breadth of response has lots of different lymphocytes that see different parts of the virus, making it very tricky for the virus to completely hide from them.

Omicron because a key part of its external structure that’s targeted by antibodies – the (in red in the picture above) – is heavily mutated, lessening the ability of antibodies to bind to the virus and neutralise it. However, because T cells focus on other parts of the virus, such mutations might not stop them from identifying it.

Indeed, , which is still awaiting review, suggests this is the case. This is reassuring, because the virus’s spike protein has changed a lot during the pandemic, suggesting that it could always be mutating away from the reach of antibodies. T cells, though, should be less susceptible to viral mutation. T cells designed to fight COVID also appear to be in the human body than antibodies.

But do T cells have a strong effect?

We already know a lot about the of T cells in other viral infections. This knowledge suggests that, against COVID, a good T cell response is not only needed to help B cells produce antibodies but should also create killer T cells that can broadly recognise the coronavirus, protecting against multiple variants.

Evidence directly on COVID and T cells is still being gathered. However, it’s gradually becoming clearer that T cells do seem to play a big role in COVID.

Research has shown that generating that recognise a range of viral features with a strong response against the disease. Generating good amounts of broadly reactive killer T cells in particular seems to make COVID .

Conversely, a poor T cell response with worse outcomes for patients. Indeed, some people who have had severe COVID have been found to have in their T cell response.

A common feature of many of the studies demonstrating the effectiveness of T cells in COVID is the need for a wide breadth of response – having T cells (and B cells) that recognise multiple features of the virus. It’s thought that this could be the key to experiencing milder disease.

This breadth might even extend beyond this coronavirus specifically. The COVID virus is a betacoronavirus, and there are several betacoronaviruses that already infect us, including ones that cause the common cold. Shared features between these cold-causing viruses and COVID may mean that T cells we already had against the cold against COVID now. in both and is being uncovered.

What does this mean for vaccines?

Many of the vaccines designed to date – including Moderna’s, Pfizer’s and AstraZeneca’s – have focused on just one major target on the coronavirus: its spike protein. These vaccines have been tremendously effective at generating antibodies. They also stimulate a T cell response to the spike.

But now that we understand more about the role of T cells, the importance of having a broad T cell response, and the issue of antibodies waning, perhaps we should consider refocusing our vaccine strategies on generating T cells and on targeting more than just one protein.

Work is moving in this direction. of that can trigger much more broadly reactive helper and killer T cell responses have been completed, and several other are also .

These T cell vaccines may be the key to boosting existing immunity and generating long-lived protection against severe disease from a whole range of COVID variants. If so, they would be a huge part of the world living more safely with COVID.

, Professor in Biomedical Sciences,

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Many diets originate in a system for rating foods according to the effect they have on our blood sugar level. This way of characterising food came from at the University of Toronto back in 1981. They gave each type of food a score according to how much it raised blood sugar levels, with sugar as the benchmark, with a score of 100. Honey scored 87, sweetcorn scored 59, tomato soup 38, and so on. Today, every conceivable edible thing has been analysed this way and countless diet plans have built on this way of ranking food. Generally, those seeking to lose weight are advised to avoid foods that cause blood sugar levels to spike.

But we’ve all come across someone who seems to stay at a healthy weight no matter how much cake, chocolate or wine they consume. And this – the differences between us – is where vital advances are now being made, leading us to a new understanding of what the best diet plan really is.

In 2015, Eran Elinav and Eran Segal at the Weizmann Institute of Science in Israel . They recruited 800 participants, and instead of taking glucose measurements a few times over the course of a few hours, as was done in 1981, every participant’s blood sugar level was measured every five minutes over seven days, using a small sensor developed for people with diabetes. As well as this, each participant answered a detailed medical questionnaire, were subject to a variety of physical assessments, such as measurements of their height and hip circumference, and they all had their stool analysed for the types of bacteria they contain.

It turned out that glucose levels spiked exactly in accordance with earlier research. But crucially, this was only the case on average. The variation from one person to the next was enormous.

For any given food, some people’s glucose levels would spike dramatically, while others hardly seemed to react at all. This couldn’t be explained away as a random fluctuation because the same person responded similarly each time they ate that particular food. For one middle-aged woman, for example, her blood glucose level spiked every time she ate tomatoes. Another person spiked especially strongly after eating bananas.

Segal’s wife, Keren, was . As a dietitian, she had been trained to provide guidance to countless people about what they should and shouldn’t eat. Now her husband had evidence that her dietary advice might not have always been helpful. The fact that some people’s post-eating sugar levels spiked more in response to rice than ice cream was shocking to her. It dawned on her that she might have even directed some of her patients to a type of food that, though beneficial on average, was wrong for them personally.

A machine-learning algorithm (a type of artificial intelligence) was used to figure out which factors needed to be considered to generate the most accurate forecast of a person’s post-meal glucose response. One factor stood out as the most significant contributor by far: the types of bacteria found in their stool, which reflects their .

Exquisitely complex

So what does this mean? It means that there is no single best diet plan – everything is personal. What constitutes a healthy diet plan depends on who is eating it: their genetics, their lifestyle, their microbiome, perhaps even the state of their immune system, their history of infections and more. Each of which is exquisitely complex on their own terms, and how they interact even more so.

Our understanding of the details – what makes a diet work or not for an individual – is still in its infancy. But in the near future, with the help of computer algorithms and big data analysis, we are surely due a revolution in the science of diet and nutrition.

If it becomes clear that personalised nutrition would have a huge impact on human health, the question will present itself: should analysis of a person’s blood and microbiome to produce a personalised diet plan become part of routine, preventative healthcare, paid for by taxation? Indeed, where would we draw the line between a nutritional product, a dietary plan and a medicine? As any science matures, new policies must be developed. This will be especially important when it concerns such a vital part of our daily lives: .

, Professor of Immunology,

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This is surprising given that, from the get-go, public health strategies to reduce the spread of COVID-19 recognized workplaces as potential . Witness the that workers work from home if possible and, if not, be protected through masking, shielding, screening, distancing and other protective measures. Yet collecting information about work among those who tested positive for COVID-19 was minimal and inconsistent.

At the start of the pandemic, the collection of work information in many jurisdictions was limited to whether someone was a health-care worker or not. That was largely out of concern about transmission from workers to patients, not worker-to-worker or worker-to-community transmission.

If we had, from the early days of the pandemic, routinely and systematically collected information from COVID-positive people about their work, we would have enhanced our understanding of the role of workplaces in the spread of COVID-19, the relative importance of the potential routes of COVID-19 transmission and the effectiveness — or not — of mitigation strategies.

We would also have been able to identify with much more certainty the non-health-care workplace settings in which COVID-19 spread was and was not occurring, potentially allowing more people to continue working at the workplace with minimal risk.

The three of us came to the realization that our respective countries were similar in their limited collection of workplace-related information during the pandemic when we worked together on a panel presentation for the . The congress, which took place virtually Sept. 20-23, was co-hosted in Canada by the .

Here are three things we believe need to happen to mount a more effective public health response to pandemics in the future.

1. Routinely capture information about work in public health databases

Public health databases should collect information on the occupation, the industry in which they work and the name or location of the workplace of infected people. (Unsplash/Jason Goodman)

Health agencies, including hospitals, health units and infectious disease surveillance programs, need to routinely capture relevant information about work when assessing a person’s health or treating a health condition. At a minimum, these systems should collect information on if the person is working, their occupation, the industry in which they work and the name or location of the workplace.

During the COVID-19 pandemic this should have been further extended to whether they were at their workplace during the period when they were infected, or if their workplace was closed or they were working from home. This data would help gauge the effectiveness of these protective measures.

This is not simple. Accepted systems of classifying occupations and industries are complex. To get information that can be used at a policy level, the classification of occupation and industry must be done consistently across databases. Training health agencies to do this should start now.

2. Consider workplace exposures within a continuum of exposures

Where people work and what work they do intersect with many other determinants of health. They inform the length of their commute to work, the transportation they take and the type of housing and community they live in. Occupations, and occupational risks of infectious diseases, are not randomly distributed across racial, sex, immigration or age groups.

We’ve also learned from the pandemic that risk is , including home, community, transportation and work settings. Almost all settings have some risk. The degree of risk depends on factors such as proximity to others, interactions with the public, masking compliance, adequacy of ventilation, environment (indoor or outdoor), potential viral load, transmissibility of infected persons and more.

 A full parking lot at an Amazon fulfilment centre in Mississauga, Ont., during the during the COVID-19 pandemic in April 2021. Infection risk is continuous across settings, including home, transportation and work settings. THE CANADIAN PRESS/Nathan Denette

A consistent challenge throughout the pandemic has been trying to understand the relative contribution of workplaces versus other settings within the continuum of exposure. A study awaiting peer review looked at workplace outbreak estimates in Ontario. It found that in many industry settings, the risk of COVID-19 due to a workplace outbreak was .

In the U.K., an identified that it wasn’t necessarily the specific work activities that led to the outbreak, but activities associated with work such as car sharing or eating together in lunchrooms. However, given differences in identifying and defining workplace outbreaks, outbreak estimates are likely conservative in many jurisdictions.

3. Maintain and expand connections between public and occupational health agencies

Work is an important component of many . Yet, traditionally, government departments focused on workplace health and those focused on health-care delivery and public health have operated in silos. COVID-19 forced occupational health and safety and public health to work more closely together, and each learned the important contributions the other can make. We need to formalize and continue these collaborations going forward.

The COVID-19 pandemic has shone a spotlight on the importance of work on health outcomes. Without better work data about people who have tested positive, we remain in the dark about where and how to target prevention measures for a potentially important route of transmission.

, Senior Scientist, Institute for Work & Health. Associate professor, Dalla Lana School of Public Health, ; , Chief Scientific Adviser, Honorary Professor, , and , Research epidemiologist, Instructor,

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A therapy for infants showing early signs of autism reduces the chance of the child meeting diagnostic criteria for autism at three years of age. That’s according to our new research, published today in the journal .

Therapy for children with autism often begins after receiving a diagnosis, which usually doesn’t occur until after the child turns two.

Our findings suggest starting therapy during the first year of life, when the brain and mind are developing rapidly, may provide even greater benefits.

Infants who received the therapy at 12 months of age were re-assessed at age three. They had fewer behaviours of autism, such as social communication difficulties and repetitive behaviours, compared to infants who didn’t receive the therapy.

Infants who received the therapy were also less likely to meet criteria for an overall diagnosis of autism when they were three.

Autism diagnosis

Like all neurodevelopmental conditions, autism is diagnosed using “deficit-focused” diagnostic criteria. In other words, children are assessed on what they can’t do.

The is the authoritative guide describing the behaviours we use to diagnose neurodevelopmental and psychiatric conditions. It specifies individuals must have “persistent deficits” in social communication and behavioural interaction to receive a diagnosis of autism spectrum.

Significantly more children are now recognised as having difficulties learning social communication skills than previously. This has led to an increase in the numbers of children being diagnosed with autism – now estimated to be .

These social and communication difficulties, restricted behavioural repertoire and sensory issues, can present significant barriers to relationships, education and employment as they mature. So reducing these challenges can be important to helping individuals thrive into adulthood.

The aim of the therapy we trialled in our study was to help support social communication skills early in life, with the aim of reducing these long-term barriers.

The therapy

The therapy, called iBASIS-VIPP, was based on the (VIPP) program. This program was adapted by our colleagues in the United Kingdom to specifically support social communication development.

The therapy is parent-led, which means parents and caregivers, who are the most prominent and important people in their babies’ lives, are trained to deliver it.

iBASIS-VIPP uses video-feedback to help parents recognise their baby’s communication cues so they can respond in a way that builds their social communication development.

Parents are taught to recognise their baby’s communication cues.

Parents are videoed interacting with their baby in everyday situations, such as feeding and playing. The trained therapist then provides guidance to the parent about how their baby is communicating with them, and they can communicate back to have back-and-forth conversations.

We know these back-and-forth conversations are crucial to support early social communication development, and are a precursor to more complex skills, such as verbal language.

Importantly, parent-infant interactions are in no way the “cause” of autism. Infants are born with developmental vulnerabilities, which other studies tell us are likely of genetic origin.

This therapy focuses on supporting parent-child interactions as a way of enriching their social environment, creating learning opportunities for the child. And this is tailored to the child’s unique abilities.

The therapy takes the approach that children who develop differently experience the world and learn skills in different ways. By understanding unique abilities and interests of each baby, we can use these strengths as a foundation for future development.

What we found

In our study, we identified 103 infants in Perth and Melbourne who were showing early behavioural signs of autism, such as reduced eye contact, imitation or social smiling.

Fifty of the infants were randomised to receive the iBASIS-VIPP therapy for five months. The other 53 infants received the usual services they would receive in their local community, such as allied health therapy, working with psychologists, speech pathologists and occupational therapists.

The babies then received developmental assessments at around 18 months of age, two years, and three years.

When the babies were aged three, independent clinicians who did not know which therapies the children had received, reviewed all of the developmental information collected. And they determined whether the children met diagnostic criteria for autism.

Half the babies in the study received the therapy, with the other half treated as usual.

The iBASIS-VIPP therapy was so effective in supporting children to learn social communication skills that only 6.7% of the children met diagnostic criteria for autism at age three years, compared to 20.5% of children who did not receive the therapy. That’s a reduction of two-thirds.

While most children in the study still had some level of developmental difficulties, the therapy supported the development of social communication skills. This meant they no longer met the criteria for a diagnosis.

The iBASIS-VIPP therapy led to increased parental responsiveness to their child’s unique communication. It also improved parent-reported language development, compared to the control group.

This is the first time a “pre-emptive” therapy – that is, a therapy provided before diagnosis – has shown an effect on autism diagnostic outcomes.

What do the findings mean?

This therapy represents a new way of providing support to infants showing early developmental difficulties.

Many therapies for autism try to improve development by working with children directly to shape more “typical” behaviours.

By contrast, this therapy does not work with the child directly but with the social environment around the child. It adapts to each child’s unique differences, and helps them learn in a way that is best for them.

By doing so, this therapy was able to support social communication skills and behavioural expression to the point that infants were less likely to meet the “deficit-focused” diagnostic criteria for autism.

Each child is different and treatment needs to be tailored to them.

This finding provides strong evidence for a new model of how we provide clinical support to children with developmental differences.

Rather than waiting until a diagnosis to start therapy – typically at two years of age at the earliest – we need to identify developmental differences as early as possible. Then we need to provide developmental supports that nurture each child’s strengths.

At its most basic, this is a change of clinical support from “wait and see” to “identify and act”.

The finding also emphasises the importance of providing supports to children based on functional difficulties, rather than the presence or absence of a diagnosis. This approach is consistent with Australia’s .

By understanding who a child is (their strengths and challenges) rather than what they are (a diagnostic label), we can provide individualised therapy supports that will help them towards their full potential.

, Bennett Chair of Autism, Telethon Kids Institute, ; , Professor of Child/Adolescent Psychiatry, , and , Associate Professor of Developmental Psychology,

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– including – are now offering third COVID-19 shots amid reports of vaccines proving less effective over time. But do these countries really need to embark on widespread booster campaigns? Here’s what research tells us so far about how vaccines are performing.

One study suggests that after four months of the second dose, the Pfizer/BioNTech vaccine is less effective at preventing infection (classified as a positive PCR test), with protection falling from . However, the research is a preprint, meaning that its results have yet to be formally reviewed by other scientists.

Similarly, real-life data from suggests that over-60s who received their second dose of the Pfizer vaccine in March 2021 were 1.6 times better protected against infection than those who received their second dose two months earlier. However, the data was less clear cut when looking across other age groups. This study also hasn’t yet been peer reviewed.

Data for the Moderna vaccine shows that functional antibodies (those able to stop viruses from entering cells) persisted in most people for six . However, there was a gradual decrease in performance against the beta variant of the virus, and the study didn’t assess the vaccine against the now-dominant delta variant.

A has looked at vaccine effectiveness against delta, and found both the Oxford/AstraZeneca and Pfizer vaccines were less effective at preventing infection when facing this variant. Similar findings by the US Centers for Disease Control and Prevention.

While all these studies may sound alarming, most are yet to be formally reviewed, so their results need to be treated with caution. They also measure different things. Some look at numbers of positive PCR tests rather than symptoms or disease. Others consider antibody levels or the response to different variants. Really, we need to consider what the most important goals of vaccination are when assessing performance.

Vaccines still protective

An ideal vaccine would completely prevent infection and so stop people catching and spreading the virus. However, earlier on in the pandemic, appeared of people being reinfected with COVID-19 as well as of – and high levels of antibodies are thought to be important in preventing infection from starting. So it’s been suspected for a while that creating a vaccine that completely blocks infection wouldn’t be possible.

Indeed, antibodies are just one indicator of an effective immune response. We also need T lymphocytes that kill the virus, and immune memory to enable us to quickly produce lots of these killer T cells and antibody-producing B cells. Here the news is . Studies have shown that both killer T cells and immune memory persist well.

What this could mean is that some people might not have enough antibodies to completely prevent infection, but can still fight the infection off and stop it from taking hold. If this were the case, you would expect vaccines to reduce the impact or severity of disease. And this is where we are seeing good news.

Reports in the and the are showing fewer vaccinated people requiring hospitalisation or developing severe symptoms from the delta variant. For example, fully vaccinated people in the US to be five times less likely to get COVID-19 and ten times less likely to be hospitalised or die from it.

Similarly, the mentioned above showed that in people aged 40-59, four months after vaccination, vaccines were 98% effective at preventing people from being hospitalised with COVID-19. After six months, protection remained high, at 94%.

For people over the age of 60, though, the data shows a bigger drop off in performance, with protection against hospitalisation lower after four months (91%) and six months (86%). This difference may be due to older people being less able to following vaccination, as well as the challenge of the delta variant.

However, what’s clear is that the vaccines are highly effective at protecting against severe disease compared with those who have not had a vaccine. And this, really, is the most important goal of vaccination – to stop people getting dangerously ill and dying.

Turning on the boosters

Despite protection against severe disease remaining high many months after vaccination, a number of governments have chosen to launch vaccine booster programmes. Will the third doses being rolled out by the UK and other governments be sufficient to provide long-term and even more highly protective immunity in the most vulnerable? The truth is, we don’t yet know.

We should remember that vaccination is just one of the ways we protect ourselves from infection, and that maybe other measures, such as mask wearing and ventilation, will still be needed if we cannot achieve sufficient protection. Indeed, as well as boosters, the British government has also for reintroducing home working and mask wearing over the winter should the virus threaten to get out of hand.

The other question we have to ask ourselves is whether we should actually be looking to help other vulnerable people across the world. It’s been estimated that the richest countries have more than already, even if boosters are used and children are vaccinated.

The most important goal of vaccination is to protect against severe disease and death, yet many countries a first vaccine dose, enabling the virus to thrive at a huge cost to lives. Really, can we look the other way?

, Professor in Biomedical Sciences,

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By  ,

Every few years, the Intergovernmental Panel on Climate Change (IPCC) – the United Nation’s climate science body – produces a major report on the state of the climate crisis. However you slice it, the told the world what it already knew – and added even greater urgency.

Like the last two in and , the doesn’t say it directly in the text, but you can clearly infer from the numbers that to have anything like a decent chance of limiting warming to 1.5°C – the goal of 2015’s – global emissions need to peak by around 2025 and then plunge rapidly towards zero. We had 11 years to reach that peak and turn it around. Now we have four.

The report sets out five different pathways that emissions could take in the coming decades, with different “climate futures” attached to them. The pathway in which emissions fall as fast as possible gives us a bit less than a 50% chance of limiting warming to 1.5°C. In this scenario, the world has to limit total greenhouse gas emissions over time to the equivalent of around 500 gigatonnes of carbon dioxide (CO₂).

The report shows that at the moment, the world emits around 40 gigatonnes a year (and growing). That leaves about 12.5 years of emitting at current levels. So if the world reaches zero emissions by 2050, in each year until then, emissions must be no higher than 40% of 2021’s emissions on average.

To get emissions to peak and then start on a downward trend is fairly simple in theory. There are several major changes that can be made in sectors like electricity, construction and transport, where lots of emissions come from, and where there are readily available alternatives. These include:

• A ban on new fossil fuel infrastructure. No new , no new operations, and no airport expansions. In essence, the world could agree a .

• Existing coal plants could be rapidly replaced with sources of energy, like windfarms.

• Radical improvements could be made in the .

• Natural gas could be eliminated in buildings, replaced with heating and cooking which use .

• could be decarbonised by a shift to electric vehicles (cars, trucks, buses, trains) and from cars to bikes, walking and public transport.

Fewer cars, more cycling.

Achieving all of this in ten years is technically possible. But there are significant obstacles which are fundamentally political.

What’s the hold-up?

Fossil fuel companies to prevent action that threatens their profitability, lobbying governments to and to . They have enough support in enough countries – think , , and – and enough countries with contradictory interests – , the , the and – to stall action in a range of forums, as in the latest . Even in countries with relatively strong climate policies, the power of the fossil fuel industry generates various contradictions, as in the for North Sea oil and gas.

Global inequalities in emissions remain an important issue to deal with too. There are in developing countries but emissions in most industrialised nations. Peaking emissions globally means curbing emissions growth in and other countries, with much more rapid declines in the US, UK and Germany than the global average. The politics of this are delicate and complicated.

Then there is the question of how to finance this rapid shift. This entails mobilising investment in renewable energy, doing huge amounts of retrofitting buildings for energy efficiency and electrification, and accelerating the construction of electric vehicle infrastructure. It also entails significant global financing of such transitions in developing countries. But how should this money be mobilised?

The neoliberal consensus of the last four decades favours private finance. But leaving this effort to the free market is likely to be inadequate. Fossil fuels are often than renewables, despite the latter’s cost-competitiveness. Reviving notions of public finance to generate sufficient investment in low-carbon sectors may be necessary. There has been some shift towards this approach in the emergence of green new deals in different countries, but a much bigger push in this direction is needed.

And of course, the world remains distracted by other crises. The most obvious of these is COVID-19, which has in most countries, delaying new policy announcements, focusing attention on both the pandemic and the economic recovery. The level of investment needed to overcome COVID-19 has presented some , but the evidence so far seems to suggest that the world economy is bouncing back towards .

Meanwhile, COVID-19 has reduced the pressure on political leaders to act on climate change. It has been much harder to organise the protest movements – the school strikes, Extinction Rebellion – that were burgeoning before lockdowns came into force globally.

The pandemic has cost the climate movement precious momentum.

The importance of COP26

The IPCC report will be used to inform the discussions of world leaders at the UN climate talks, otherwise known as , which are to be held in Glasgow in November 2021. But if there are so many things preventing putting emissions on a downward trajectory, what can the world expect from this fortnight-long meeting?

Clearly it can do some things. It is the key site for negotiating global inequalities, such as how richer countries should compensate poorer ones for having to bear the brunt of a crisis largely not of their making. Such issues have dogged the UN climate process since negotiations started in 1991. It is where national governments are supposed to make new sets of commitments, known as nationally determined contributions, to meet the overall goal of the Paris Agreement’s proposed global temperature limit.

Some of these commitments have already been published, that they are significantly strengthening global action are not good. So far, and despite in April, there is no sense that leading states are successfully persuading each other to improve their commitments, generating the kind of momentum in 2015 which led to the Paris Agreement.

To expect much from COP26 itself is to miss the key sites of action involved in causing emissions to peak and decline however. In the Paris Agreement, these are national governments. And most of the conflicts preventing action occur within countries.

It’s at this level that people must focus much of their attention, to outweigh the influence of fossil fuel companies, find novel ways to fund decarbonisation and steer the economic recovery from COVID-19 towards a low-carbon future.

, Professor of International Politics,

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Most COVID-19 vaccines require two doses, and the usual strategy is to give people the same vaccine type for both. But the , led by the University of Oxford, recruited over 800 participants from across the UK to investigate the effects of giving people different vaccines for their first and second jabs. Two vaccines were studied: those made by Pfizer and AstraZeneca.

So, is mix and match an option? The are preliminary, having yet to be reviewed by other scientists, but the answer appears to be yes. Giving people different types of COVID-19 vaccine appears not only to be safe, but also a potential way of boosting protection against the coronavirus.

However, the exact benefits depend on which vaccine goes first and which second. Taking the AstraZeneca vaccine followed by the Pfizer one resulted in a striking increase in antibodies against the coronavirus’s spike protein (a key part of its outer structure) compared to using the AstraZeneca vaccine for both doses or Pfizer followed by AstraZeneca.

Taking the AstraZeneca vaccine followed by Pfizer resulted in a better T cell response than all other combinations of doses. T cells – also known as – are immune cells that help kill invading germs (such as the coronavirus) and support antibody production.

The Com-Cov study will next look at whether mixing and matching doses like this provides as good results when a larger gap is left between doses. The time between doses in this initial trial was 28 days, but a parallel study is stretching this to 84 days. The results are yet to be reported.

An expected outcome?

Other researchers have also been studying mixing vaccine types to fight COVID-19. A recently reported that people who initially received the AstraZeneca vaccine experienced a massive increase to their antiviral immunity when given a second dose of the Pfizer vaccine – providing more evidence that Pfizer works well as a booster.

The body may mount an immune response against vaccines themselves – particularly those that use adenoviruses for delivery.

To understand why these beneficial effects might be happening, it’s important to understand how the AstraZeneca and Pfizer vaccines work. Both present a key element of the coronavirus – again, the – to the immune system, but do so using different methods.

The Pfizer approach packs the genetic code for the coronavirus’s spike protein into fatty nanoparticles. When these particles enter the body’s cells, the code is read and copies of the spike protein are produced, leading to an immune response. The AstraZeneca vaccine delivers the same genetic code but uses a weakened form of a common cold virus (an adenovirus) from chimpanzees to carry the code into cells.

When the first vaccine doses are given, it is possible that an immune response is raised not just against the spike protein created, but also against the carriers that are used to deliver the code for it. This is a for treatments or vaccines that use viruses for delivery. If the second dose is then the same, the immunity developed against the carrier will react against the second dose, clearing some of it before robust, protective and long-lasting immunity develops.

This is why Russia’s Sputnik V vaccine – which is based on the same delivery method as the AstraZeneca vaccine – uses two different adenoviruses as carriers for its first and second doses, and has achieved .

Why mixing doses is so important

There are additional benefits to mixing vaccine doses on top of improving protection. Logistical problems can arise when a second vaccine dose has to be identical to the first. Producing double the quantity of one vaccine takes time. Boosting with a different vaccine could allow the world’s population to be vaccinated quicker.

Next we need to see what happens when mixing COVID-19 vaccines from other manufacturers.

Second, if a person reacts badly to their first vaccination, they are more likely to get a second dose if they know it is a different one – and it’s clear that for good protection. Governments may also decide a certain type of vaccine is less suitable for different groups of people, as with the AstraZeneca vaccine in younger people in some countries. Having more potential vaccine combinations available may help overcome any public uncertainty in the wake of these sorts of decisions.

Supplying vaccines to some low- and middle-income countries can also be difficult, particularly if they do not have the necessary cold storage requirements for large batches of a vaccine that need to be kept at low temperatures. Including vaccines into the distribution plan that do not need storage at very low temperatures may make widespread vaccine delivery easier.

So there are clearly huge benefits to vaccine mixing. However, this study only looked at two vaccine types – in time, every combination will need to be tested, in every age group and in every ethnicity. Vaccines may also behave differently if mixed in different contexts, for example, against a backdrop of malnutrition or other infectious diseases. These factors will need to be included in future testing too. But for now, this study suggests that a mix-and-match approach to COVID-19 vaccines is an acceptable, useful option.

, Professor of Inflammatory Disease,

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To fully vaccinate all adults is going to take a final big push. For it to be successful, those responsible for the vaccine rollout need to ensure that the public are sufficiently capable, have sufficient opportunity, and are sufficiently motivated to take the vaccine.

Capability is about having the knowledge and skills to take up the vaccine. For example, some people might not have had enough information to convince them that the vaccine is safe. They may not know when, where and how to get the vaccine. Or they may not be able to make plans to have the vaccine.

Opportunity is about having the necessary conditions to take up the vaccine. For example, someone might not have the encouragement or social support from family and friends. Or the vaccine might not be available in their region, so they don’t have the opportunity to be immunised.

Motivation is about having the desire to have the vaccine. For example, some people might not believe the vaccine will protect them from COVID-19, or they may not be able to overcome their .

People differ in their capabilities, opportunities and motivations, so steps to increase vaccination uptake need to target the appropriate barrier. For example, it is not helpful to tell people about the positive outcomes of COVID-19 vaccination if the vaccination isn’t available to them. It would be irresponsible to increase people’s fear by telling them about the health risks of not vaccinating but not ensure they can easily get to the vaccination centres at a time that’s convenient for them.

New guidance

Researchers in the UK recently about what works to encourage people to take up vaccinations in pandemics and epidemics. They found that the focus of previous interventions were mainly on changing capability (explaining why vaccines are safe and correcting misunderstandings) and motivation (telling people about the benefits of vaccination). There was little in the interventions that seemed to address opportunities.

This research formed the basis of a , written by the British Psychological Society, to be considered by people in public health when trying to get people to have the vaccine. It recognised that people’s capability, opportunity and motivation to take up the vaccine differed because of factors that are often outside of people’s control.

For example, some countries have low opportunity because of the cost of the vaccine prevents mass vaccination. Some people may have low capability as there may not be enough information about vaccine safety for their particular group – for example, pregnant women. And some people may have low motivation if they are afraid of leaving the home after shielding.

A person can have different capability, opportunity and motivation over time. For instance, some may worry more about vaccine safety for the first dose but have problems with opportunity, because of a lack of local vaccination sites, for the second dose. Public health experts need to address all of these barriers to ensure that people can have the vaccine so we can all be protected from COVID-19 and get back to normal life.

, Lecturer in Health Psychology,

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Some viruses, such as , can cause hearing difficulties, but what about SARS-CoV-2, the virus that causes COVID-19?

In the first few months of the pandemic, a of COVID-19 and hearing difficulties revealed a possible link between COVID-19 and audio-vestibular symptoms (hearing loss, tinnitus and vertigo). However, both the quantity and quality of the early studies were low. Now that the pandemic has been with us for over a year, more studies have been published and researchers have been able to estimate how common these symptoms might be.

have identified about 60 studies that report audio-vestibular problems in people with confirmed COVID-19. Our analysis of the pooled data, published in the , reveals that 7%-15% of adults diagnosed with COVID-19 report audio-vestibular symptoms. The most common symptom is tinnitus (ringing in the ears) followed by hearing difficulties and vertigo.

Tinnitus

Tinnitus is a common condition, affecting around 17% of all adults. Most people with tinnitus also have hearing loss, suggesting a close link between the two. In fact, tinnitus is often the first warning that, for instance, exposure to loud noise or drugs that are toxic to the ear has damaged the hearing system. Interestingly, that tinnitus is a common symptom of long COVID, which is where symptoms last weeks or months after the infection has gone.

The hearing organ is clearly extremely sensitive because will experience temporary tinnitus if they are in a very quiet environment. There are also strong links between . If people lie awake at night, stressed and anxious because of an impending deadline, financial concerns or bereavement, it is not uncommon that they will find themselves attending to noises in their ears.

This usually becomes less bothersome when the source of the stress and anxiety is removed. Surprisingly, there are no clinical tests that can diagnose tinnitus, so hearing specialists rely on self-reports.

Why tinnitus is being reported in people with confirmed COVID-19 is unclear. It is possible the virus attacks and damages the auditory system. On the other hand, the mental and emotional stress of the pandemic may be the trigger. But we need to be careful when interpreting these findings as it’s not always clear if studies are reporting existing or new symptoms. What is lacking are good-quality studies that compare tinnitus in people with and without COVID-19.

Hearing loss and vertigo

Hearing difficulties associated with COVID-19 have been reported across a wide age range and COVID-19 severity, ranging from mild (and managed at home) to severe (requiring hospitalisation). There are several case reports of sudden loss of hearing in one ear, often accompanied by tinnitus.

Sudden hearing loss occurs in around . It is treated with steroids to reduce swelling and inflammation in the inner ear. But the treatment only tends to work if it is started soon after the hearing loss occurs.

We know that viruses can cause sudden hearing loss, so SARS-CoV-2 may be responsible for the of hearing loss in COVID patients. Yet the number of COVID-19 cases worldwide is so high that it is difficult to say with any great certainty if the cases of sudden hearing loss are higher than what we would generally expect to see each year.

Another commonly reported symptom of COVID-19 is dizziness. It can be quite difficult to differentiate this from the rotatory vertigo that is characteristic of damage to the balance system in the inner ear. However, the best estimate is that rotatory vertigo occurs in around 7% of COVID-19 cases.

Start of our understanding

Given the importance of providing timely evidence to inform health services, the information from this new systematic review is to be welcomed, but so far, the evidence is based on surveys and case reports. It is important not to diagnose audio-vestibular symptoms where they do not exist or where they are coincidental, given the high rates of COVID-19 in the population. However, the findings of the review might simply reflect the start of our understanding of this emergent health condition.

What is lacking are carefully conducted clinical and diagnostic studies that compare a sample of people who tested positive for COVID-19 and a sample of non-COVID controls. To that end, we are leading a year-long study to investigate the long-term effect of COVID-19 on the audio-vestibular system among people who have been previously in hospital with the virus.

, Ewing Professor of Audiology,

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To understand whether immunity is possible – and why this has even been questioned – it is important to consider the nature of SARS-CoV-2. It is a betacoronavirus, and several betacoronaviruses already circulate widely in humans – they are most familiar to us as a cause of the common cold. However, immunity to cold-causing viruses is not long-lasting, leading many researchers to question whether longer term immunity to SARS-CoV-2 is possible.

However, studies considering the closely related betacoronaviruses that cause the diseases and offer a glimmer of hope. With these viruses, immunity has proved more durable. Could this be true for immunity to SARS-CoV-2 too?

Well-trained protection

The first of the body’s immune cells to respond to an infection are designed to attack the invading substances to try to control the infection’s spread and limit the damage done. The immune cells that respond later that are responsible for immunity are known as lymphocytes, which include . Lymphocytes need time to learn to identify the threat that they are facing, but once trained they can be rapidly deployed to seek and destroy the virus.

Our T cells and B cells work together to combat infection, but they have quite different functions that enable them to deal with a huge variety of threats. B cells make antibodies that neutralise infections. T cells are broadly divided into two types – T helper cells and cytotoxic T cells. Cytotoxic T cells directly kill viruses and cells that viruses have infected. T helper cells support the functioning of B cells and cytotoxic T cells. Collectively these are known as “effector” cells.

Studies have now demonstrated the that these effector cells play in the fight against COVID-19. Once the infection is gone, these cells should then die off in order to avoid causing excessive damage in the body.

But some effector cells persist. In an yet to be reviewed by other scientists, functional T cells have been detected six months after infection. Similarly, even patients who have had have detectable antibodies six to nine months . However, antibodies do wane over time, so these antibodies against SARS-CoV-2 could eventually disappear.

Remembering the danger

Such discoveries raise real optimism about protection from reinfection. But what happens if or when effector lymphocyte levels finally drop off? Well, our immune system has another trick up its sleeve to protect us for the long term, even after people’s effector cells and antibody levels have fallen. Once lymphocytes have been trained to deal with a virus, a pool of the cells remember it and are kept for the future. These “memory” cells can then be rapidly deployed if the threat is encountered again.

Memory cells are incredibly powerful tools for our immune system and can be very long-lived, with studies showing memory B cells for smallpox persisting at least 60 years after and for Spanish flu at least 90 years after the . In order to understand whether long-term immunity to SARS-CoV-2 is possible, it’s therefore critical to consider not just effector cells but all types of memory cells – B, T helper and cytotoxic T memory cells.

Fortunately, memory cells can be identified by specific structures and proteins that they express on their surfaces, enabling researchers to distinguish them from effector cells. Now that COVID-19 has been with us for a year, researchers are becoming able to make great leaps in understanding about memory responses to COVID-19. Evidence is emerging of lasting six to nine months after infection, and a recent preprint study (yet to be reviewed by other scientists) has also identified what appear to be .

Studies have also been investigating whether prior exposure to the virus confers protection, with showing that in the UK’s second wave, previously infected health workers were either completely protected from reinfection or were asymptomatic if they picked up the virus again. Such observational studies give real hope for the durability and potential of protective immunity.

We still have much to learn about the immunology of COVID-19, but the pace of research is astounding, and the more we learn, the more we are empowered to beat this virus. Our immune system is incredibly powerful, and these studies showing persistent immune responses nine months after infection are real cause for celebration. They give us confidence that, with vaccination, we have a real chance to win the war against COVID-19.

, Professor in Biomedical Sciences,

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The COVID-19 lockdown upturned the lives of teenagers at a time when they are usually becoming more independent and taking steps toward their future. Instead, they were confined to their homes, exams were cancelled, and their next steps looked suddenly less certain.

Our research on – Teenagers’ Experiences of Life in Lockdown – explored how 109 UK-based 16 to 19-year-olds coped under coronavirus restrictions, with an emphasis on their wellbeing.

show that lockdown was an intense, challenging experience, raising feelings of loss and fear about the future. However, participants also described considerable effort to adapt, actively working to counter the negative personal impact of the lockdown and trying to think positively.

Coping with stress

Our participants described feeling overwhelmed and trapped, fearful about COVID-19, missing people that they couldn’t see face to face, and feeling uncertain about the future. Many teenagers found that milestones they had worked towards for years, such as exams, were suddenly gone. “When it was announced that GCSEs were cancelled, I was distraught,” one participant told us.

For some, being confined in family homes was distressing:

I’ve already got a history of mental health issues, being shoved into a house with none of my friends and any sense of normality shredded has certainly not helped.

They also expressed some mistrust and frustration with the government and media in lockdown. Some felt that the government was being vague about restrictions and easing the lockdown too soon, and this was making them feel anxious generally but also worried about the return to education:

I am unsure if I want to go back in September because I’m unsure that the government has the best supervisions.

Participants in the study reported often assessing the impact that the lockdown was having on them, and then proactively finding self-care and coping strategies to specifically counteract these negatives.

This included finding ways to distract themselves and escape, in order to avoid negative thoughts, and finding ways to relax, to counter difficult feelings and stress – such as engaging in hobbies, exercising, and spending time with (or virtually with) loved ones.

Our participants generally described working to ensure their coping strategies were in line with restrictions, although this sometimes caused conflict when household members disagreed about what was allowed and what was not.

For instance, one participant explained: “[Some days I’ll] go for a walk with a friend. However, [I] come back to face confrontation with my brother as he believes that to be unsafe.”

Staying positive

Teenagers told us they were attempting to stay optimistic. Many identified positive opportunities in lockdown, such as time to learn new skills and deepen relationships with their families. Some used lockdown to evaluate their lives, identifying things they appreciated and things they’d like to change.

Teenagers reported that spending time with family was a positive aspect of lockdown.

They also worked on creating routine and goals, as their days had lost structure and purpose, and being kind to themselves – with recognition that the situation was inherently stressful.

One teenager told us:

If I didn’t keep myself busy with the baby [brother], films or sketching I would allow the loneliness to consume me.

Teenagers reported taking up exercise at home.

Of course, self-care isn’t always easy. Some participants felt less able to look after themselves, and others described strategies they thought were problematic, like smoking or suppressing their feelings.

Participants often expressed gratitude for their circumstances, noting they were lucky to have resources such as access to outdoor spaces or positive relationships in their household:

I am very grateful for the position I am in, I generally get along well with my family and, with mum and dad working from home, we have been able to stay safe.

Hope for the future seemed important. Participants focused on what life would be like after lockdown and the things they would do. However, some were growing less hopeful about the pandemic ending soon, and felt disheartened:

I know it can be hard during such worrying times to be optimistic or hopeful but I think that it is really important that we remind each other that this is only temporary and that the best thing to do is just keep going forward.

Supporting teenagers

Our findings highlight the capacity for adaptation among our teenagers, offering a clear demonstration of resilience in the face of the pandemic.

On the one hand, this adaptation shows we must not underestimate the resourcefulness of teenagers. Supporting their emotional wellbeing at this time should include recognising and celebrating this, encouraging teenagers to reflect and feel empowered by their adaptation to the pandemic.

However, we cannot shift ultimate responsibility for their wellbeing onto teenagers themselves. Resilience depends on , such as family life, education, recreation, and healthcare. COVID-19 has in many ways to many of these systems.

Teenagers need to be given the tools they need to actively cope and should be supported when they are struggling. This can include having opportunities to reflect on and discuss how they are feeling, seeing those around them make use of healthy coping responses, and having time and space to relax and care for their own needs.

It will be extremely important to provide hope for the future for teenagers as the pandemic continues to unfold. Without a sense of promise for a future they can look forward to, adaptation and optimism may well become increasingly difficult.

, Lecturer in Psychology of Education, ; , PhD researcher in Education and Mental Health, ; , Lecturer in Psychology, ; , Research assistant in Psychology and Education, , and , Reader in Counselling Psychology,

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If antibodies fade over time, how worried should we be? Does this mean we cannot be immune to COVID-19? To answer this question, we need first to consider what antibodies are and what they can tell us about immunity.

When we are infected, our immune system quickly responds to try and contain the threat and minimise the damage infection causes. This initial stage of immune reactivity is covered by immune cells known as innate cells that are resident in our tissues, which use a range of fairly generic strategies to both recognise and kill off the infection. But to truly deal with an infectious challenge, we need another part of our immune system – our lymphocytes.

Lymphocytes are more flexible cells that are “educated” to recognise and target a specific infectious agent. They come in – B lymphocytes, which make antibodies, and T lymphocytes, which can help the B cell response or directly kill the germs. Crucially, T and B lymphocytes work together to eradicate an infection.

Once a threat has been managed, a pool of these educated lymphocytes that know how to deal with that specific germ survive. These are known as memory cells. Memory cells are remarkably long-lived, patrolling our body ready for when they might again be needed. This whole system of lymphocyte responses is known as our adaptive immune response, and antibodies are only a portion of it.

So to properly understand and measure immunity after an infection, you would ideally assess both T and B lymphocytes and then see what happens when people face the same infection. But while testing for these cells is possible, it is expensive and impractical in large numbers of people, requiring costly reagents and detailed testing protocols.

As antibodies can be readily measured in blood samples, they are often used instead as an indication of whether there has been a good adaptive immune response. Over time, though, the levels of antibodies in our blood naturally fall – but this doesn’t necessarily mean protection is lost. Some of those educated memory cells should remain, including memory B cells that can quickly make more antibodies if needed. So the findings from React2 don’t necessarily mean that people are losing immunity to COVID-19.

For instance, have also looked at T cells and found in patients who have recovered from mild and severe COVID-19. We can therefore be somewhat optimistic that we could have some lasting protection against this disease.

We can also look at other viruses for clues. COVID-19 is caused by a beta coronavirus. There are several beta coronaviruses common in the human population – those that are most familiar cause the common cold. Long-lasting immunity to these cold-causing viruses , but immunity to more serious conditions caused by other beta coronaviruses – Mers and Sars – is . We do not yet know if immunity to the virus causing COVID-19 will be more akin to Sars or the cold-causing viruses, but the potential for longer lasting immunity to Sars and Mers offers some hope.

Finally, the React2 study looks at what happens after natural infections, but we should keep in mind that immunity generated by a vaccine might not be the same. Lymphocytes recognise germs by selecting some of their unique features to remember and react to and this matching process can be influenced by many factors, such as how the features are presented to lymphocytes or the available lymphocytes that recognise that feature. Although this allows for massive flexibility in the germs that can be recognised, it might not always result in the best viral killing in the future.

But with a vaccine, you can instead select the best bits of the pathogen to target in order to provoke the most effective T and B lymphocyte responses, which could in turn provoke bigger and better memory responses. This is being factored into the , with several vaccine candidates already being shown to promote .

Some vaccines are focusing the immune system on targeting the coronavirus’s spike proteins, shown here in orange.

However, if there is longer lasting immunity, it may not be present across all groups of people. Some, such as the elderly, are disproportionately affected by COVID-19, and the React2 study showed that older people had a . These results may be explained by the fact that many older people have – including the B lymphocytes needed for antibody protection.

Such findings emphasise the need to look at diverse groups of people to fully understand if immunity to COVID-19 is possible, particularly when developing vaccines. This is exactly what is being assessed in the happening now. Right now, we shouldn’t be overly worried. COVID-19 is a giant puzzle we are gradually unlocking. Every piece of the puzzle we master contributes to our growing knowledge and ability to beat this infection.

, Professor in Biomedical Sciences,

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To date, there have been of COVID-19 reinfection, with various other unverified accounts from around the world. Although this is a comparably small fraction of known to have been infected, should we be concerned? To unpick this puzzle, we must first consider what we mean by immunity.

How immunity works

When we are infected with any pathogen, our immune system quickly responds to try to contain the threat and minimise any damage. Our first line of defence is from immune cells, known as innate cells. These cells are not usually enough to eliminate a threat, which is where having a more flexible “adaptive” immune response comes into play – our lymphocytes.

Lymphocytes come in two main varieties: B lymphocytes, which make antibodies, and T lymphocytes, which include cells that directly kill the germy invaders.

As antibodies are readily measured in blood, they are often used to indicate a good adaptive immune response. However, over time, antibodies levels in our blood wane, but this doesn’t necessarily mean protection is lost. We retain some lymphocytes that know how to deal with the threat – our memory cells. Memory cells are remarkably long-lived, patrolling our body, ready to spring into action when needed.

Vaccines work by creating memory cells without the risk of a potentially fatal infection. In an ideal world, it would be relatively easy to create immunity, but it’s not always that straightforward.

Although our immune system has evolved to deal with a huge variety of pathogens, these germs have also evolved to hide from the immune system. This arms race means that some pathogens such as malaria or HIV are very tricky to deal with.

Infections that have spilled over from animals -– zoonotic diseases –- are also challenging for our immune system because they can be completely novel. The virus that causes COVID-19 is such a zoonotic disease, originating in .

COVID-19 is caused by a betacoronavirus. Several betacoronaviruses are already common in the human population – most familiar as a cause of the common cold. Immunity to these cold-causing viruses isn’t that but immunity to the more serious conditions, Mers and , is more durable.

Data to date on COVID-19 shows that antibodies can be detected three months after infection, although, as with Sars and Mers, antibodies gradually decrease .

Of course, antibody levels are not the only indication of immunity and don’t tell us about T lymphocytes or our memory cells. The virus causing COVID-19 is structurally similar to , so perhaps we can be more optimistic about a more durable protective response – time will tell. So how worried then should we be about reports of reinfection with COVID-19?

How worried should we be?

The handful of case reports on reinfection with COVID-19 don’t necessarily mean that immunity is not occurring. Issues with testing could account for some reports because “virus” can be detected after infection and . The tests look for viral RNA (the virus’s genetic material), and viral RNA that cannot cause infection can be shed from the body even after the person has recovered.

Conversely, false-negative results happen when the sample used in testing contains insufficient viral material to be detected – for example, because the virus is at a very low level in the body. Such apparent negative results may account for cases in which the interval between the first and second infection is short. It is hugely important, therefore, to use additional measures, such as viral sequencing and immune indicators.

Reinfection, even in immunity, can happen, but usually this would be mild or asymptomatic because the immune response protects against the worst effects. Consistent with this is that most verified cases of reinfection reported either no or mild symptoms. However, one of the latest verified cases of reinfection – which happened just 48 days after the initial infection – actually had a more severe response to .

What might account for the worse symptoms the second time round? One possibility is the patient did not mount a robust adaptive immune response first time round and that their initial infection was largely contained by the innate immune response (the first line of defence). One way to monitor this would be to assess the antibody response as the type of antibody detected can tell us something about the timing of infection. But unfortunately, antibody results were not analysed in the recent patient’s first infection.

Another explanation is that different viral strains caused the infections with a subsequent impact on immunity. Genetic sequencing did show differences in viral strains, but it isn’t known if this equated to altered immune recognition. Many viruses share structural features, enabling immune responses to one virus to protect against a similar virus. This has been suggested to account for the lack of symptoms in young children who frequently get colds caused by betacoronaviruses.

However, a , yet to be peer-reviewed, found that protection against cold-causing coronaviruses did not protect against COVID-19. In fact, antibodies recognising similar viruses can be dangerous – accounting for the rare phenomenon of antibody-dependent enhancement of disease (ADE). ADE occurs when antibodies enhance viral infection of cells with potentially life-threatening consequences.

It should be emphasised, though, that antibodies are only one indicator of immunity and we have no data on either T lymphocytes or memory cells in these cases. What these cases emphasise is a need to standardised approaches in order to capture the critical information for robust evaluation of the threat of reinfection.

We are still learning about the immune response to COVID-19, and every piece of new data is helping us unpick the puzzle of this challenging virus. Our immune system is a powerful ally in the fight against infection, and only by unlocking it can we ultimately hope to defeat COVID-19.

, Professor in Biomedical Sciences,

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Every living human is controlled by an internal “clock” which drives our circadian rhythm – the natural internal process that regulates our sleep-wake cycle during a 24-hour period. This internal clock controls most of our body processes over this period, including our sleep cycle, digestion, metabolism, appetite and immunity.

External light levels, eating times and physical activity all act to keep the body clock synchronised to the external environment. Every cell in our body also has its own clock, which helps keep these processes working so seamlessly. For example, clocks in individual tissues, such as the liver, work to ensure timely supply of energy to the rest of the body.

But our circadian rhythm can be disrupted by any number of factors, including going to bed later than usual, or eating late at night. While occasional disruptions are no cause for alarm, research shows that long-term circadian rhythm disruption can cause poor health. For example, many studies have found that regular shift work increases the and . And unfortunately, is becoming more common in our society, thanks in part to light pollution, noise and electronic devices, all of which could increase instances of these chronic health conditions.

But why is the body able to manage one-off instances of circadian rhythm disruption – such as staying up late on the weekend, or eating a late-night meal – without any health consequences? Our looking at how the circadian rhythm controls metabolic processes to match our daily patterns of food intake holds the answer.

Liver gene ‘clock’

One important component of our body clock is a protein called REVERBα. It is one of the network of proteins which keeps our body clock “ticking” in each organ of the body. However, natural genetic variation of the REVERBα gene is in humans. Research has also found that mice in all tissues accumulate fat in and around their organs – and can become very obese when given a fatty diet.

We wanted to study more closely the action of REVERBα in the liver, as the liver is critical for maintaining energy balance, and its function is highly circadian, to cope with fasting during sleep. To do this, we used a new type of genetically modified mouse with the only in the liver.

To our surprise, we discovered that deleting REVERBα has relatively little impact. In particular, we didn’t see the accumulation of fat in the liver that we were expecting, and which is seen in animals which lack REVERBα in all tissues. However, when we mapped liver genes that were likely to be under the control of REVERBα, we found thousands – including genes that are major regulators of energy and fat metabolism.

So we had a paradox: a circadian clock regulator with an extensive range of targets in the liver, yet it was not essential for normal liver function. This raised two important issues. First, that under normal conditions REVERBα is ready, but not required to regulate fat metabolism. And second, that the earlier findings linking REVERBα to obesity (and to the accumulation of fat in multiple organs) might actually arise from body-wide cues.

Specifically, we thought that eating at unexpected times may be the cause for obesity. This is because mice lacking REVERBα throughout their body had an irregular eating pattern, especially feeding during their rest, or sleep period.

To test this idea, we analysed what happened when mice with REVERBα deleted in the liver were subjected to disrupted feeding schedules, rather like how shift work disrupts eating schedules. Here, we discovered that disordered feeding caused a major change in the expression of genes that control fat metabolism – but only when REVERBα was deleted from the liver. This suggests that REVERBα acts to smooth out the effects of disordered eating, as shown in our diagram below.

How REVERBα stops circadian rhythm ‘disruptions’

SOURCE NAME, Author provided

In this way, all the internal clocks embedded in our body’s tissues serve to protect against occasional changes in behaviour (such as the odd late-night meal). However, when we are constantly doing things that go against our natural circadian rhythm – such as always eating late, or working night shifts – this protective system is overwhelmed, leading to obesity and diabetes.

Our study therefore highlights the importance of eating meals in sync with the body clock, during the day. To keep our liver clock ticking – and to keep our whole circadian rhythm working properly – it’s important to develop an eating schedule that has a clear separation between the fed period (typically during the day), and the fasted period (typically during the night). This is hard for shift workers, depending on shift schedule, so strategies to help are urgently needed.

, Professor of Endocrinology, ; , Professor of Physiology, , and , Lecturer in Endocrinology & Diabetes,

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So it’s alarming that hospitals in the UK – – saw the number of people attending with suspected stroke fall during the pandemic. Although it’s possible that fewer people were having strokes during the outbreak, the concern is that people with a stroke were not using hospital services when in need.

In response to this, investigated changing stroke attendance between January and May 2020 in Greater Swagֱ��, and the possible reasons behind this.

Hospital visits significantly down

The Greater Swagֱ�� and Eastern Cheshire region contains three hyperacute stroke units. Together, they admit approximately in England, Wales and Northern Ireland.

During March 2020, a 16% drop in the number of people admitted with stroke and a 21% drop in people coming to hospital following transient ischaemic attacks (TIAs) – also known as “”. Overall, fewer people were arriving with less severe strokes, whereas attendance with moderate to very severe stroke remained consistent.

The reasons for a reduction in milder strokes presenting at hospital aren’t clear. In parallel to the pandemic, the UK’s quarantine and lockdown measures influenced lifestyle factors, environmental factors and attitudes towards seeking healthcare, all of which could be associated with reducing stroke activity.

Clean air and clean living

Reduced numbers of patients presenting to hospital could simply be due to fewer strokes and TIAs occurring in the population. such as diet and exercise habits are associated with stroke risk – and anecdotal evidence suggested both positive and negative lifestyle changes occurred during the spring. Sales of and both increased.

But it’s difficult to determine if these increases translated to a relative change at the individual level. Was there an increase in alcohol consumed, or did supermarket sales simply replace alcohol sales in bars and restaurants? And did people use their new exercise equipment? Regardless, it’s thought unlikely that such changes would have had such an immediate influence on stroke risk.

Despite shops selling more alcohol, overall beer sales were down this spring, suggesting people drink differently at home.

Environmental factors could also have had an influence. and have previously been associated with increased immediate risk of stroke. Levels of nitrogen dioxide, one of the primary traffic-related emissions, were . However, in our study, adjusting for changes in nitrogen dioxide and air temperature didn’t appear to account for the change in stroke activity.

Were fewer people seeking help?

The alternative is that strokes and TIAs were occurring at the same rate in the population, but fewer people went to hospital. This seems the more likely reason for the change in recorded strokes, though we can’t be sure.

Patients having had a TIA or who have mild stroke symptoms may see improvement within 24 hours, which may encourage them to delay seeking help. Such patients from a GP, family or friends before reaching out for further medical assistance.

But under social distancing, self-isolation and shielding, identifying symptoms and seeking advice may have been difficult, especially if GPs were also under restrictions. The fear of getting infected or diverting resources away from more urgent needs may also have made people reluctant to seek medical care, particularly for milder or transient strokes.

China also in stroke activity during the pandemic, and one study has shown that some with stroke symptoms. We shouldn’t jump to conclusions, but this suggests it’s possible that stroke victims in the UK avoided hospitals when the pandemic was at its worst. Equally, we can’t yet rule out other factors influencing China’s lower rate of stroke admissions either.

But while it is plausible that stroke patients were missed during the early months of the pandemic, it’s going to be very difficult to prove this. The true population-level incidence of stroke is difficult to estimate at the best of times, and this year’s estimates will probably be more unreliable than usual (national stroke reporting was disrupted) and may be .

Stroke activity within the UK healthcare system now appears to be returning to normal. But with social restrictions now again being imposed it’s important to reiterate the for identifying symptoms and seeking help. A stroke, regardless of how mild it may appear, is a medical emergency. Early identification and accessing appropriate care can make all the difference.

, Lecturer in Biostatistics, ; , Associate Visiting Lecturer, , and , Professor of Stroke Medicine,

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Young people with chronic health conditions cope with all of the usual challenges of growing up – making friends, changing schools, adapting to new situations, developing a sense of self, and dealing with interpersonal conflict. But they also have to deal with the challenges of their illness.

Young people with (IBD), a group of chronic conditions that includes Crohn’s disease and ulcerative colitis, have to deal with unpleasant symptoms, intrusive treatment and uncertainty. include diarrhoea, abdominal pain, weight loss, blood in their stools and fatigue. The disease can go into remission, but there is no cure and flare-ups can result in hospital stays and missing school or work.

Findings from on mental health among young people with IBD show that when experiencing symptoms, some young people feel negatively about their friendships because they are embarrassed about their condition. And we found that this can lead to loneliness along with depression and anxiety.

‘Hiding my condition’

Many young people with IBD choose to conceal their diagnosis from friends and colleagues. found this is often out of a desire to present themselves as “normal” along with wanting to keep health issues private for fear of being judged.

Being diagnosed with IBD can create an abrupt shift in a young person’s expected biography, derailing their plans and expectations of life. Challenges to our identity are difficult to manage at any age, but can be particularly hard for as they transition towards .

Some young people we talked to said they feared being stigmatised because of their condition – which has been shown to happen to . This can be a key concern for young people with IBD, particularly just after diagnosis and during major life transitions such as moving schools, going to university, or starting a job.

To disclose or not

In , all of the young people had told at least one friend something about their IBD. Mostly their decision to tell had been their choice. But, visible indicators of their condition, such as a , meant several young people felt compelled to disclose.

For such long-term chronic conditions, disclosure is ongoing and young people must make decisions throughout their life about what to disclose (or not) as they meet new people and enter into new situations. And although the of talking about bowels is being challenged, there is still a strong sense that toilet habits are awkward to talk about.

Many of the young people we spoke to said their friendships were important but they struggled with knowing how much to share.

Starting a conversation about IBD was described as “tricky” and young people had to judge who they could trust – typically close friends – and how much to share. They generally avoided going into “too much detail”, or “making a big a thing about it” but also wanted friends to know it isn’t “just an upset stomach” as one young woman explained:

It’s hard to explain colitis, it’s the hardest thing in the world, still now after so many years. It’s not just an upset tummy, it’s the whole body and lots more complications and medication.

Some young people told stories of negative reactions from friends arising from misconceptions about IBD. Some friends worried they could catch IBD. Others were scared by the word “disease” or did not want to be friends with someone who was “different to them”. Some young people’s friendships were severed. Yet many found their friends to be supportive and their friendship ties strengthened.

What helps?

about their and sharing images of previously hidden aspects of treatment – such as – young people are breaking down taboos and reducing the sense of isolation that can come with having a chronic health condition.

But while challenging social stigma is essential, our study also shows how important it is for young people with IBD to look after their – and friendships can be a key part of this. This is why we’ve worked with young people to come up with the “” resources, that will hopefully help other young people with Crohn’s or colitis talk to their friends about their condition.

It’s also important to highlight that our findings show that despite the struggles young people with IBD experience, none of them wanted to be or felt defined by their condition. They have the same concerns, aspirations and desires as other young people, and ultimately just want to be seen as normal – whatever that might look like.

, Professor of Children's Nursing, ; , Research fellow, , and , Professor of Psychology for Education,

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However, in our – in which we’re exploring public attitudes to COVID-19 and social distancing – we’re finding that people are stigmatising those who might have the disease or might transmit it. At its core, this stigmatisation is based on what social scientists call . This is where we define, often negatively, certain individuals or groups in terms of how they are different from us. Othering is at the root of stereotyping and discrimination.

Most if not all infectious diseases are stigmatising to some extent, precisely because coming into contact with those who have the disease may lead to us becoming sick. But the fact that COVID-19 is a new disease with no cure or vaccine – and (compared say to flu) has a case fatality rate – adds to the fear factor that often drives othering. Stigma can also, as we are seeing in this pandemic, potentially undermine efforts to control and fight disease.

How stigma is playing out

shows that what were once relatively innocuous behaviours like coughing and sneezing are now being experienced as significant, dramatic, anxiety-provoking events. For example, one participant, who has a long-term cough from being a smoker, reported feeling as though they were being treated like a “leper” while out shopping.

Not wearing a mask in public divides public opinion – but face coverings are soon to become compulsory in UK shops.

Another participant, a hay fever sufferer, reported feeling “on edge” going out for fear of sneezing and worrying over what people might think or say. Many of our participants also described strong reactions to others’ coughs and sneezes in public spaces:

It’s interesting how we have gone from being polite and saying “bless you” to now having to defend people’s coughs and sneezes. If somebody does cough, it draws a really strong negative reaction towards them.

Often these reactions were expressed as anger toward those getting too close or not adhering to new social norms, such as sneezing into the elbow. We’ve also seen general condemnation of those perceived not to be adhering to social distancing rules, for example by getting too close to others in shops or on pavements. Of course, where distancing and hygiene guidelines are being blatantly flouted, frustration and anger are arguably both expected and justified.

There is also a broader form of othering taking place between people with different interpretations of the guidelines, or between those who have differing opinions over whether those guidelines are too cautious or not cautious enough. For example, in we found a general division between those who were keen to be “living completely as normal” as soon as possible and those who felt things were moving too fast. Those who were taking advantage of or stretching the guidelines were deemed “inconsiderate” and a source of “frustration”.

As we continue to emerge from lockdown and socially reintegrate, the rules on how to behave – and what we can and can’t do in public – are getting increasingly complex. We can expect new forms of social division and social stigma to emerge as a result.

The wider negative impact

The worry is that this divisiveness will deepen over the course of the pandemic as measures continue to ease. The real problem is that official guidelines have often lacked clarity. It’s little wonder that the recent government equivocation around facemasks is a source of contention. Conversely, clear guidelines can help to reduce othering and divisiveness by reducing confusion and uncertainty around what is or isn’t acceptable.

There’s a clear need to avoid social division. Research on past pandemics has shown how stigma can detection and treatment efforts, cooperation with contact tracing and isolation measures, and the effective distribution of resources for disease prevention and control. In the current climate, if stigma is associated with having COVID-19, then some people may be reluctant to report symptoms, take a test or input information into a contact-tracing app.

For example, in we found that one of the initial misconceptions some people had about contact-tracing apps – and one of the reasons they wouldn’t consider using them – was that the app might allow users to specifically identify others (or be identified themselves) as having COVID-19 (though this ).

One participant said about the app: “It’s like being branded with a horrendous black mark. I could look and be like, ‘my friend, my neighbour has COVID’.” Another participant felt as though “it could cause hate crime as well, finding out ‘oh, you know, I got it from this person’”.

These views reveal implicit assumptions around COVID-19 being something shameful, socially undesirable, and a potential cause of discrimination and social exclusion. And they demonstrate the power of stigma to undermine efforts to control the virus through the government’s track and trace programme.

There is, though, some guidance available on reducing stigma. Past research on other diseases such as and , as well as advice from organisations like and the , offer a number of lessons. Avoiding military metaphors (such as the “war” on COVID-19 and there being COVID-19 “victims”), addressing misinformation surrounding the disease, and not allowing a person’s identity to be defined by having COVID-19 can all have a positive effect.

, Senior Lecturer in People and Organisation, and , Lecturer in Psychology and Mental Health, Swagֱ��

A copy of their peer reviewed study published in BMJ Open is now available : 

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