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Researchers identify a potential biomarker for long COVID

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A team of US researchers has identified a potential biomarker for long COVID.

If the findings of their study are confirmed by other research centres, the biomarker could be the first specific and quantifiable indicator for confirming long COVID.

Currently, clinicians confer a diagnosis of long COVID based upon a collection of symptoms that patients develop after SARS-CoV-2 infection.

William Stringer, M.D. is a Lundquist Institute investigator and senior author on the study.

He said: “If a patient arrives in clinic and they relate the persistence of typical signs and symptoms of long COVID, 12 weeks or more after COVID -19 infection, I give them a presumptive diagnosis, but I don’t have any blood tests or biomarkers to confirm this diagnosis.”

The study results, reported in the journal Infection, detail the detection of SARS-CoV-2 protein fragments within extracellular vesicles (EVs) — tiny, naturally occurring packages that help cells share proteins, metabolites, and other materials.

The researchers collected and analysed blood samples from 14 patients over 12 weeks of aerobic exercise training (56 samples in all) in a clinical trial led by Stringer in long COVID.

The researchers found 65 distinct protein fragments from SARS-CoV-2 inside the EVs.

These fragments come from the virus’s Pp1ab protein, an RNA Replicase enzyme which is key to how the virus copies itself and makes other viral particles.

This protein is found uniquely in SARS-CoV-2, and not in uninfected human cells, noted Asghar Abbasi, Ph.D., a Lundquist Institute investigator and first author of the study.

Significantly, the researchers found that these viral peptides were demonstrated in each subject, but not each blood draw, in the EVs of Long COVID patients and were not detected in a separate control group of pre-pandemic EV samples.

These findings add to growing evidence that suggests that SARS-CoV-2 may persist in certain body tissues long after the initial infection.

Some groups hypothesize these lingering viral reservoirs could play a role in Long COVID.

How the virus reaches tissues without its usual entry points—such as the brain—remains an open question, and may be related to EV particles.

Abbasi said: “We thought that maybe if the virus is circulating or moving in the body, we should try to see if EVs are carrying those viral fragments.”

This idea became part of an ongoing clinical trial led by Drs. Abbasi and Stringer, which was already studying EVs to see if they are linked to changes in immune function related to exercise and post-exertional malaise, a common symptom in these patients.

Patrick Pirrotte, Ph.D. is associate professor at TGen, director of the Integrated Mass Spectrometry Shared Resource at TGen and City of Hope, and co-senior author of the study.

He said: “While promising, the molecular signal of the viral peptides within the study samples was observed to be subtle and not consistently detected at every blood collection time point.

“There’s still a lot to unpack that we don’t know at this point.”

For instance, he added, the researchers don’t know if the exercise itself drives the expression of viral programs intracellularly, and then those viral programs result in proteins that are going to be shed, or if there is a permanent reservoir in those cells, and it’s just a matter of detecting it at a certain time point.

Although the identified peptides originated from one of the virus’ largest proteins, the researchers did not detect other comparably large proteins indicative of active viral replication.

It’s possible that the peptides contained in the EVs are just molecular “trash” leftover after the formation of new viral proteins.

Stringer said: “We haven’t run [our tests] on people without long COVID symptoms who are currently, or who were, infected with COVID.

“This raises the question: is this just continuing to take out the trash from the COVID infected cell or is this really ongoing replication someplace?

“I think that’s the mechanistic issue that needs to be resolved in future studies.”

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Researchers use prehistoric skeletons to study ageing

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An archaeologist from the University of York is leading a new study into how societies viewed ageing, wisdom and experience over thousands of years.

Dr Lindsey Büster’s research claims to be the first to focus on the lives and experiences of older adults in prehistoric and Roman Europe, examining skeletons and objects from collections including York Museums Trust.

The project, called Age-Old Stories, aims to challenge existing stereotypes and ageism by exploring how earlier societies viewed age, wisdom and experience.

“They have a very large collection of Roman human remains from across Yorkshire and that’s going to be a really important assemblage for us,” said Dr Büster.

The ultimate aim is for the research to provide strong examples of why making older adults more visible in policy-making and public life is so important,” said Dr Büster.

“Ageing is not a marginal experience, it is a central part of human history and we should have better strategies for valuing and celebrating it today.”

Archaeological discoveries already suggest that older adults were central figures in many past societies.

In Scarborough, the remains of Gristhorpe Man – Britain’s best-preserved Early Bronze Age skeleton – were analysed and suggested he was aged between 45 and 60 years, tall and muscular, and nourished by a rich diet.

“He is over 45 and he was buried in this log coffin, which would’ve been hugely time consuming, hugely labour intensive and he’s buried with a dagger,” said Dr Büster.

“These are all the trappings of a high-status individual.”

The project will work in partnership with York Museums Trust to create a new exhibition and public events, and will also collaborate with Age Friendly York.

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Weight loss jabs should be first-line obesity treatment in most cases, new guidance states

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Weight loss jabs Mounjaro and Wegovy are so effective they should be the first treatment for obesity “in almost all cases”, according to new medical guidance.

The European Association for the Study of Obesity praised the drugs’ effectiveness and wider health benefits in new guidance to doctors.

It described them as slimming aids that can also cut the risk of related conditions such as high blood pressure and type 2 diabetes.

Three in ten Britons – around 16m adults – are obese, but only 1.5m use the injections, most bought privately at about £200 a month.

Trials have shown adults using semaglutide, the active ingredient in Wegovy and Ozempic, lost about 14 per cent of their body weight over 72 weeks.

Those taking tirzepatide – marketed as Mounjaro and sometimes dubbed the “king kong” of weight loss jabs – lost about 20 per cent over the same period.

Dr Andreea Ciudin, co-first author of the guidance from the Autonomous University of Barcelona, said the drugs were “completely transforming care of obesity and its complications”.

She added: “Even though there are several options on the market, the reality is that semaglutide and tirzepatide are so effective that they should be the first choice in almost all cases.”

The guidelines were produced by an international team of experts, including contributors from the UK.

They analysed existing studies and created an algorithm to help doctors decide the best treatment based on a patient’s weight and associated conditions.

They concluded that tirzepatide and semaglutide should be considered the “medications of choice” when a substantial level of total body weight loss is required.

When a lesser degree of weight loss is the aim, other medicines such as liraglutide, naltrexone–bupropion and phentermine–topiramate may be appropriate.

The guidance comes after health secretary Wes Streeting pledged this week to make injections available to millions more patients on the NHS.

Speaking at the Labour Party conference in Liverpool, he said it was unfair that wealthier people had been able to benefit from the drugs’ “transformative” effects “on their health, their confidence and their quality of life” while those unable to pay privately had gone without.

He added: “Weight-loss jabs could help us finally defeat obesity.

“Our mission is to ensure that the best science, the best healthcare and the best innovations are available not just to some, but to all.”

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Brain shape changes could offer early warning signs of dementia, study suggests

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Ageing alters the brain’s shape in measurable ways that could provide early warning signs of dementia, potentially years before symptoms appear, researchers say.

Analysis of more than 2,600 brain scans from adults aged 30 to 97 revealed significant alterations in brain geometry linked to declines in memory, reasoning and other cognitive functions.

The inferior and anterior parts of the brain expanded outward, while the superior and posterior regions contracted inward. These uneven shifts were most evident in older adults showing cognitive decline.

Researchers at the University of California, Irvine’s Centre for the Neurobiology of Learning and Memory found that people with more pronounced posterior compression performed worse in reasoning tests, suggesting these geometric markers directly relate to brain function.

“Most studies of brain ageing focus on how much tissue is lost in different regions,” said Niels Janssen, senior author and professor at Universidad de La Laguna in Spain and visiting faculty at the CNLM.

“What we found is that the overall shape of the brain shifts in systematic ways, and those shifts are closely tied to whether someone shows cognitive impairment.”

One important implication involves the entorhinal cortex – a small but vital memory hub in the medial temporal lobe.

The study suggests age-related reshaping may press this region against the hard base of the skull.

The entorhinal cortex is one of the first areas where tau, a toxic protein linked to Alzheimer’s disease, accumulates.

The findings raise the possibility that mechanical and gravitational forces may contribute to its vulnerability in Alzheimer’s – a potential disease mechanism not previously considered.

“This could help explain why the entorhinal cortex is ground zero of Alzheimer’s pathology,” said study co-author Michael Yassa, director of the CNLM and James L McGaugh endowed chair.

“If the ageing brain is gradually shifting in a way that squeezes this fragile region against a rigid boundary, it may create the perfect storm for damage to take root. U

“nderstanding that process gives us a whole new way to think about the mechanisms of Alzheimer’s disease and the possibility of early detection.”

The researchers say their geometric approach could eventually provide new markers for identifying dementia risk, potentially before symptoms emerge.

“This isn’t just about measuring brain shrinkage,” added Janssen.

“It’s about seeing how the brain’s architecture responds to ageing and how that architecture predicts who is more likely to struggle with memory and thinking.”

The patterns were replicated in two independent datasets, reinforcing the consistency of these shape changes as a hallmark of ageing.

“We’re just beginning to unlock how brain geometry shapes disease,” said Yassa.

“But this research shows that the answers may be hiding in plain sight – in the shape of the brain itself.”

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