Your B’s and T’s: How they reflect COVID-19 infection

24th August 2022 – By Aaruthy Suthahar

Antigen and positive Covid-19 blood sample

TwinsUK researchers have found that your B cell and T cell responses are linked to COVID-19 infection.  

The immune system is made up of lots of different cells and organs that help your body fight off infections. B cells create antibodies, which neutralise viruses, with the help of T cells. Doctors and scientists have been using antibody tests to find people with previous COVID-19 infections, particularly for research. The TwinsUK team wanted to see if T-Cell tests would be a helpful addition, or replacement, for antibody tests. This is particularly important now many people cannot access PCR (swab) tests from the NHS when they think they have COVID-19.  

The study looked at T-cell responses in participants who did or did not have a positive antibody response to the virus that causes COVID-19 (SARS-CoV-2) in participants who were symptomatic and asymptomatic during the COVID-19 pandemic. 

The team gathered data from the TwinsUK cohort who participated in the home visit study and the COVID Symptom Study cohort. They were put into groups based on if they presented symptoms associated with COVID or not, and if they had taken part in TwinsUK’s antibody testing during the first wave in the UK in Spring 2020.  

There were 32 participants who were part of the final analysis. None of the 17 participants without antibodies showed a T cell response, when their blood was tested against peptides specific to the virus. 14 out of the 15 participants who had antibodies against COVID-19 experienced a T cell response.  Therefore, the study found that there was a strong correlation between antibody responses, and T cell responses to the peptides specific to SARS-CoV-2. Also, individuals who were symptomatic, but didn’t have antibodies after the infection wave in Spring 2020, had no proof of T cell memory of COVID-19 infection either. 

The researchers also found no evidence of cellular immunity suggestive of COVID-19 infection in individuals with COVID-19-like symptoms but negative antibodies. 

First author Dr Marc Österdahl said: 

“Now that access to COVID-19 PCR testing is restricted, it is important for the public, doctors and researchers to know how we can pick-up previous COVID-19 infection. The standard is IgG Spike antibody testing, but not everyone who had symptoms that looked like COVID-19 showed antibodies. 

We wanted to know if T-Cell testing, which is more expensive and complicated, would be needed to pick up all cases. However, in people who had symptoms in recent months, antibody and T-Cell responses are strongly linked, and T-Cell testing didn’t add any benefit. This suggests that the established IgG Spike test is best, and that symptoms in antibody negative people might be from another similar illness.”  

Study explores how belly fat increases risk of metabolic disease

19th July 2022 – King’s College London

Changes that occur in the body in response to an increase in belly fat have been put under the microscope as part of a study from TwinsUK, offering new insight into the cause of metabolic disease.

The study, led by King’s College London researchers Dr Jordana Bell and Colette Christiansen and published in the medical journal Genome Medicine, looked at how epigenetic marks (measures of how the human body reads DNA to affect the way genes work) in fat tissue change as belly fat accumulates.

Using samples from 538 TwinsUK participants and combining genetic, gene function, diet, and health data, the researchers examined epigenetic marks across the genome (the complete set of a person’s genetic material) and found nine genes that are highly relevant to metabolic disease risk.

Among these was a gene where the identified epigenetic changes were recognised as a potential mechanism through which diet can affect belly fat accumulation, as well as other epigenetic marks that translate genetic risk effects on metabolic health.

The findings also allowed the researchers to characterise the molecular changes that occur because of an increase in belly fat and the impact these changes have on gene function and insulin resistance.

Dr Jordana Bell, reader in Epigenomics in the School of Life Course & Population Sciences said:

“With rapidly rising rates of obesity worldwide, it is important that we understand how elevated body fat affects us at the molecular level and how this translates to metabolic disease risk,”

Metabolic diseases – the most common of which is diabetes – disrupt normal metabolism or the process of converting food to energy on a cellular level.

While previous studies in this field have explored the role of epigenetic marks in overall obesity using body mass index (BMI), the build-up of belly fat deep within the abdomen is known to be a greater risk factor for metabolic disease than BMI alone.

Dr Jordana Bell added:

“Our study brings us one step closer to this goal by identifying an epigenetic signature of excess belly fat, understanding its genetic and dietary triggers, and characterising its functional impacts and clinical consequences for insulin resistance,”

Based on the results of the study, the researchers also developed an epigenetic predictor of insulin resistance, relating their findings to the clinical consequences of elevated belly fat.

Colette Christiansen, PhD researcher in the School of Life Course & Population Sciences said:

“It is exciting to see that when we combine many different layers of biological information, we can start to unravel the mechanisms which drive the state of our biological health.”



Up to one in six people with COVID-19 report long COVID symptoms

29th June 2022 – King’s College London

One in six (17%) middle-aged people who report being infected by SARS-CoV-2 also report long COVID symptoms, while this falls to one in 13 (7.8%) among younger adults who reported having Covid-19, according to a new study led by King’s and UCL which is now published in Nature.

coronaviruses

The preliminary findings, part of the UKRI-NIHR funded multi-institution CONVALESCENCE study and submitted to the preprint server medRxiv, also found that women were 50% more likely to report long COVID than men, and that the risk for long COVID symptoms increases with age, is linked to poorer pre-pandemic mental and physical health and is associated with a previous diagnosis of asthma. Non-white ethnic minority groups had lower odds of reporting long COVID (about 70% less likely).

Using a stricter definition of long COVID as impacting routine daily activities, the researchers found that it affected 1.2% of 20-year-olds who had Covid-19, but 4.8% of people in middle age.

The researchers analysed anonymised data from 1.2 million primary health records across the UK together with 10 population-based cohort studies with 45,096 participants. Using existing cohort studies, whose participants are surveyed regularly, allowed the research team to include cases not reported to the GP and to look at people’s health before the pandemic.

Knowing which factors increase the risk of long COVID is an important first step in understanding how best to prevent and treat this condition.

Professor Nishi Chaturvedi (MRC Unit for Lifelong Health and Ageing at UCL), who leads the ongoing CONVALESCENCE study, said: “Getting consistent findings from this combination of many different studies gives us greater confidence that our findings are robust, which is critical given that we know so little about long COVID.”

First author Dr Ellen Thompson, of King’s College London, said:

“It’s really important to identify risk factors in the population so we can prepare and devise prevention strategies, protecting people at increased risk of poor outcomes from COVID-19.”

First author Dr Dylan Williams (MRC Unit for Lifelong Health & Ageing at UCL) said:

“Amassing this body of evidence would usually take many months or years to assemble but we achieved this more quickly through massive, constant collaboration by researchers at many different institutions.

Dr Claire Steves from the School of Life Course Sciences said:

“Our findings hint at the mechanisms behind long COVID. Next, we need to identify the predispositions that might explain, for example, why women or individuals with asthma appear to be at higher risk. Could a liability to suffer from autoimmunity or allergies play a role? Establishing concrete research avenues to go down will eventually lead to benefits for people with long COVID.”

The study forms part of the larger COVID-19 Longitudinal Health and Wellbeing National Core Study, which is investigating the health, social and economic impacts of the COVID-19 pandemic by combining rich pre-COVID data collected from participants of numerous national research studies with national anonymised electronic health records.

The researchers investigated if the risks of developing long-term Covid symptoms differed by several pre-pandemic socioeconomic and health characteristics. Coordinated analyses of the longitudinal studies and health records data showed consistently that female sex and increasing age (up to 70 years) were associated with increased odds of long COVID.

Pre-existing adverse mental health was associated with a 50% increase in the odds of reporting long COVID, while asthma was the only specific prior medical condition consistently associated with greater risk of developing lasting Covid-19 symptoms (a 32% increase). Participants were identified as having pre-existing adverse mental health if they had been diagnosed with one of a number of conditions such as depression and bipolar disorder, or their responses to questionnaires indicated they had a mental health condition before the pandemic.

Analysis was conducted on 6,899 individuals self-reporting COVID-19 from 45,096 surveyed adult participants of ongoing longitudinal studies in the UK, and on 3,327 cases assigned a long COVID code in primary care electronic health records out of 1,199,812 adults diagnosed with acute COVID-19. Long COVID, identified as Post-COVID-19 syndrome in the study, is defined as symptoms persisting for longer than 12 weeks after the initial infection.

The research team included researchers at the Universities of Bristol, Edinburgh, Glasgow, and Oxford, as well as the London School of Hygiene & Tropical Medicine, and the Bradford Royal Infirmary.

Dr Fiona Glen, programme director for the NICE Centre for Guidelines, said:

“There is still much we do not know about the long-term effects of COVID-19. We continue to monitor and assess the latest evidence on the long-term effects allowing us to continuously update our guideline recommendations. We welcome this new research which will ensure we have a better understanding of how to manage the care and treatment of patients with prolonged symptoms of COVID-19.”

HOW COVID-19 AFFECTED THE UK’S MENTAL HEALTH

TwinsUK is one of many population cohorts that form the National Core Studies Longitudinal Health and Well-being. The aim of the National Core Studies Longitudinal Health and Well-being programme is to understand the health, social and economic impacts of the COVID-19 pandemic by analysing established population cohorts, as well as national electronic health records to guide implementation of, and changes, to government policies.  

One study looked at how mental health of the UK population has evolved across the COVID-19 pandemic. The study looked at how mental health changed since before the pandemic, how experiences of mental health varied under different lockdown measures, and how the pandemic impacted already existing mental health inequalities. To address these questions, a coordinated analysis of data was carried out from 11 longitudinal population-based studies, including data from TwinsUK’s regular COVID-19 questionnaires sent to twins (known as our COPE study).  The team assessed the prevalence of poor mental health using measures of psychological distress within each cohort at 4 time periods: pre-pandemic (first lockdown Spring 2020); easing of lockdown (summer 2020) and then during a subsequent of lockdown at the end of 2020 and start of 2021.  

The info-graphics below show the key results:  

A nation in distress: There was a sustained increase in mental distress in the UK during the COVID-19 pandemic, according to results from 11 longitudinal studies.


The pandemic did not affect everyone equally: Age, sex, and education levels affected people’s experiences of the pandemic.


Age: Middle-aged people (35-44) and older people (65 and over) saw the highest increase in their distress levels.


Conclusion

Hear here! Hope for future treatments against hearing loss as researchers find 10 new genes and identify the affected ear structure

16th May 2022 – By Paz García

doctor and ear

Researchers led by Karolinska Institute, TwinsUK at King’s College London and Erasmus University have identified 10 new genes linked with hearing loss and located the part of the ear affected. 

The findings, published today in American Journal of Human Genetics, cast doubt on the dogma that age-related hearing impairment originates mainly from sensory hair cells and propose the stria vascularis in the cochlea as a new target for treatments to help people with hearing loss.  

Many people gradually lose some of their hearing ability as they get older, and an estimated 2.4 billion individuals will have some form of hearing loss by 2050. Age-related hearing impairment is a top contributor to years lived with disability and is also an important risk factor for dementia. 

The team studied genetic analyses previously carried out in centres around the world using samples from 723,266 people from 17 studies — including TwinsUK — who had clinically diagnosed or self-reported hearing impairment. The researchers identified 48 genes linked to hearing loss, including 10 new variants newly linked to hearing. 

Further analysis looking at mouse genetics indicated that age-related hearing loss is due to changes in the stria vascularis, a part of the cochlea in the ear, which is necessary for hearing. 

Co-main author Christopher R. Cederroth, Associate Professor at the Karolinska Institute, said: 

“It was hypothesized since the 1970s that the stria vascularis may play a role in hearing loss in humans, but the molecular evidence for this was missing until today.”  

Co-main author Frances Williams, Professor at King’s College London and TwinsUK researcher, said: 

“Our findings point to genes we could target for screening purposes, drug development and even gene therapy in the future. This study provides a solid foundation for ultimately improving therapies against hearing loss.” 

Bad Bacteria? Think again!

12th April 2022 – Laarayb

sphygmomanometer

We were delighted to join the I ♥ Research Academy to mentor students from local schools who were interested in science. We delivered 6 workshops with the students to teach them about how to communicate science with non-scientists. In their last workshop, the students were asked to write up a news story on one of our research articles. Below is a news story written by one of our students, Laarayb. 

Research has found a link between bacteria and hypertension, or, in other words, high blood pressure. By targeting gut bacteria, researchers can find evidence that high blood pressure can be prevented and lead to solutions to make it less prevalent.  

This remarkable research finding can help explain what makes high blood pressure more dangerous and risk-worthy, which can help treat the most complex of cases, including heart disease. 

Why should we care about this? High blood pressure can lead to extreme cases of damaged arteries and is an enormous factor in causing kidney and heart disease. It is also known that high blood pressure can cause arteries to be less elastic, reducing the amount of oxygen intake. 

Therefore, researchers conducted a study that can help us see how the amount of gut bacteria can affect levels of high blood pressure. As high blood pressure is quite common, this study is particularly important to help us understand how we can reduce the risks of disease. 

Researchers studied blood pressure and the measurements of gut bacteria of over 800 female TwinsUK participants, discovering that there were fewer types of gut bacteria in women living with high blood pressure. There were also lower levels of Ruminiclostridium 6, a type of bacteria, and more levels of Erysipelotrichacea, another type of bacteria, in women with high blood pressure. 

Due to this, the Ruminiclostridium 6 bacteria was further researched, and our innovative scientists learnt that the bacteria plays a significant role in 84 chemical processes, including ones that are linked to blood pressure. 

The researchers supported the study by stating that it will ‘be a novel means to prevent or treat hypertension’ if the gut bacteria are further researched and targeted. 

Further work should be done on participants from different ethnic groups and male participants as the majority were white, female twins, so the outcome of the study may not apply to other groups. Furthermore, more work should be done on the Ruminiclostridium 6 bacteria to find out more about its role linked to blood pressure.  

Did you know reducing your intake of vegetables can lead to decreased white blood cells?

12th April 2022 – Kira

Basket filled with vegetables

We were delighted to join the I ♥ Research Academy to mentor students from local schools who were interested in science. We delivered 6 workshops with the students to teach them about how to communicate science with non-scientists. In their last workshop, the students were asked to write up a news story on one of our research articles. Below is a news story written by one of our students, Kira.

TwinsUK has found that consuming larger amounts of vegetables, which are high in fibre and vitamins, is linked to a lower risk of having slow, long-term inflammation that lasts for painful prolonged periods.

Those who suffer from joint issues, or have even been diagnosed with arthritis, can benefit from this research study, and could potentially have a significant impact on them because they will be more informed about the effects of not eating vegetables. There is no doubt that what you eat may also be contributing to your physical well-being. This is something everyone should consider if they want to live a healthier and happier life.

Chronic inflammation occurs when your body continues sending inflammatory cells for a prolonged period after a disease or injury. This has increased lately due to the COVID-19 outbreak and therefore more people are at risk of heart disease. If this were to happen, you would gain massive amounts of white blood cells, suffer severe infections, and, develop heart disease. 

Recent research conducted by TwinsUK also considered age, gender, and BMI (Body Mass Index) when analysing 700 participants who took part in the PREDICT nutrition study found that consuming less vegetables correlates with higher white blood cell levels. The researchers did not find any correlation between fruit consumption and white blood cells; however, fruits are also healthy and a key component of your diet.  

As a result of carrying out this study, researchers demonstrated that the consumption of vegetables has a greater positive impact than people may be aware of. Finally, identifying the specific nutrients and dietary patterns that influence gut bacteria and immune cells will provide us with solutions to help reduce inflammatory processes associated with diseases such as cancer, infections, and chronic heart disease. 

What are the most popular foods and drinks at TwinsUK?

6th April 2022 – By Aaruthy Suthahar

Birds eye view of table with food (toast and chocolates) and beverages (tea).

New research has found that black tea and semi-skimmed milk are the most consumed items by TwinsUK members. The study, which aimed to understand eating patterns, also identified the top paired food items that were most consumed by twins were tomatoes and lettuce.

Researchers found that eating breakfast was not linked to an individual having a lesser or greater BMI (Body Mass Index) status or weight, even though they had a higher calorie intake. However, the team also found that individuals with a longer eating window were strongly associated with an increased BMI and weight. Diet has lots of complexities and variability, with a major effect on human health. It is not only what someone eats that can have ramifications for their health but also how and when. TwinsUK researchers have therefore been investigating the relationship between diet and disease. One key element is to understand individuals typical eating patterns and intake of nutrients. 

An EFR (Estimated Food Record) is a type of food questionnaire that allows researchers to understand eating behaviours in individuals by collecting data about all foods consumed in participants over a period. The open-ended style of an EFR means that it can more effectively identify how complex and variable individual diets are compared to methods which are more structured, including further understanding into, for example, eating patterns and of co-occurring foods.  

The researchers included 2,184 participants from our TwinsUK cohort between 2012 and 2017 and collected 2343 EFR’s from them. Twins were asked to provide information on the size of their portions, time of their meals, details of food type they consumed, date and a yes/no answer to whether they considered it a standard day’s intake. 

The team also found that twins who skipped their breakfast were reported to have a longer eating window than individuals who had breakfast, which could partly explain the lack of consistency in weight and BMI status between the individuals who had breakfast and those who skipped it. Also, time-restricted consumption, like consuming food daily within an 8-to-10-hour window, has been shown to improve glucose tolerance, although further research needs to be carried out in humans.  

One limitation of the research is that the study looked at data mostly from women. This means it is difficult to make an accurate conclusion without further clinical studies which include participants more representative of the diversity of the population in the UK.  

100 most frequently consumed food items, and food co-occurrence network of food pairings consumed within a food record

100 most frequently consumed food items, and food co-occurrence network of food pairings consumed within a food record; A 100 most frequently appearing word within food item descriptions, with the font size and colour depicting the importance of the food item B 100 most frequently appearing food item description

Can gut bacteria be linked to greenspace composition in the UK?

22nd March 2022 – By Aaruthy Suthahar

Hills and trees

The bacteria in your gut is linked to the environment around you, according to latest research from TwinsUK.  

Exposure to natural environments, also known as greenspace, has been shown to have a positive influence on our health, but the mechanisms as to why are still not clear. We know from previous research that gut bacteria is linked with inflammatory illnesses; inflammatory illnesses are also more prevalent in urban areas and in individuals who have lower levels of exposure to greenspace. Therefore, gut bacteria could act as one of the links between greenspace and health.  

The team studied 2,443 participants from the TwinsUK cohort to see if there was a difference in gut bacteria in individuals living in rural and urban environments. The researchers looked at the amount of greenspace at three different distances from a participant’s home: 800 m, 3000 m, and 5000 m. The aim was to understand if there was any evidence of bacteria differing with the amount of greenspace. 

The team found there were differences in bacteria between different greenspace areas and when comparing rural versus –urban microbes. One hypothesised reason could be that people are exposed to a range of microorganisms and therefore have a stronger immune system as they are exposed to a wider range of bacteria. Levels of bacteria associated with disease were higher in individuals living in more urban environments compared to rural environments. 

A limitation of the study was the broad interpretation of “greenspace” as being any area in a non-urban environment. This meant that factors like the accessibility of land or the type and quality of habitats that were present could not be considered. Further work could design experiments to understand this further by comparing urban areas with high, accessible greenspace with urban areas of low, accessible greenspace. 

The different microrganisms residing along the human digestive tract, along with the things these microbes produce is collectively called the human gut microbiome. It has a crucial role as it interacts with the immune system, is vital for processing nutrients and protects individuals against pathogens.  

First author Ruth Bowyer said: 

“The results show that there are geographical patterns in the composition of the microbiota which does not appear to be explained by diet, BMI (Body Mass Index), and health deficit. Therefore, the results bring to light the potential importance of considering non-lifestyle factors that could affect microbiota composition.” 

Genomic regions discovered that could help understand obesity

16th February 2022 – By Guy’s and St Thomas’ NHS Foundation Trust

DNA molecule

A new study has helped to shine light on the genetic pathways underlying obesity. The findings could help develop more personalised ways to help people maintain a healthy weight.

The work is the largest study of its kind looking at genomics and levels of metabolites – the molecules produced when the body breaks down food. It reports 74 previously unknown genomic regions that influence how people’s bodies break down food into energy.

The work was supported by the National Institute for Health Research (NIHR) Guy’s and St Thomas’ Biomedical Research Centre. The team behind the study were from the Department of Twin Research and Genetic Epidemiology, King’s College London and the NIHR BioResource.

The study involved 8,809 people who had joined the NIHR BioResource. The BioResource is a bank of individuals who consented to be contacted about research projects.

The team looked at blood samples to measure levels of 722 metabolites. These provide a snapshot of an individual’s wellbeing and the mechanisms that control key physiological processes. Metabolite levels can be affected by nutrition, drugs and the gut microbiome. However, the way the body breaks down food is known to be strongly driven by a person’s genetics.

From analysing these alongside whole genome sequencing, the team identified 202 unique genomic regions whose variations are associated with the levels of 478 different metabolites. These included 74 genomic regions not associated with any metabolites in previous works. They confirmed the findings in an independent cohort of 1,768 people.

Senior author Dr Cristina Menni from the Department of Twin Research and Genetic Epidemiology, King’s College London said:

“These results could have many practical implications. Human metabolism underlies a lot of different areas of human health and disease. Our findings could help understand certain diseases.”

“Some of the metabolites we looked at are linked to BMI and could give us an insight into obesity in some individuals. It is very early research, but in the future these findings could help to develop approaches to maintaining a healthy weight which take into account a person’s genetic profile.”

Dr Massimo Mangino, senior bio-informatician from the NHIR Guy’s and St Thomas’ Biomedical Research Centre and lead author of the study, said:

“Obesity is one of the most common conditions, and yet there’s still so much we need to understand about its biological mechanisms. Our latest findings may help to unravel some of them. Genetic studies hold real promise in helping us find new treatments for obesity. By teasing out the complex relationships between different genes, we have a huge opportunity to turn the tide against this condition.”

Dr Pirro Hysi from the Department of Twin Research and Genetic Epidemiology added:

“This study is the largest scale study of its kind of metabolite levels to date and its results enhance our knowledge of genetic mechanisms controlling human metabolism. The NIHR BioResource is a unique UK resource made possible by the amazing collaboration between doctors and researchers in the NHS. It’s because of collaborations like this that large scale studies like ours are possible.”

The World Health Organisation estimates that over four million people die each year as a result of being overweight or obese.

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