̽��ֱ�� of Cambridge - NIHR Cambridge Biomedical Research Centre

Genetic mutation in a quarter of all Labradors hard-wires them for obesity

jg533 — Wed, 06 Mar 2024 19:06:36 +0000

This obesity-driving combination means that dog owners must be particularly strict with feeding and exercising their Labradors to keep them slim.

̽��ֱ��mutation is in a gene called POMC, which plays a critical role in hunger and energy use.

Around 25% of Labradors and 66% of flatcoated retriever dogs have the POMC mutation, which researchers previously showed causes increased interest in food and risk of obesity.

̽��ֱ��new study reveals how the mutation profoundly changes the way Labradors and flatcoated retrievers behave around food. It found that although they don’t need to eat more to feel full, they are hungrier in between meals.

In addition, dogs with the POMC mutation were found to use around 25% less energy at rest than dogs without it, meaning they don’t need to consume as many calories to maintain a healthy body weight.

“We found that a mutation in the POMC gene seems to make dogs hungrier. Affected dogs tend to overeat because they get hungry between meals more quickly than dogs without the mutation,” said Dr Eleanor Raffan, a researcher in the ̽��ֱ�� of Cambridge’s Department of Physiology, Development and Neuroscience who led the study.

She added: “All owners of Labradors and flatcoated retrievers need to watch what they’re feeding these highly food-motivated dogs, to keep them a healthy weight. But dogs with this genetic mutation face a double whammy: they not only want to eat more, but also need fewer calories because they’re not burning them off as fast.”

̽��ֱ��POMC mutation was found to alter a pathway in the dogs’ brains associated with body weight regulation. ̽��ֱ��mutation triggers a starvation signal that tells their body to increase food intake and conserve energy, despite this being unnecessary.

̽��ֱ��results are published today in the journal Science Advances.

Raffan said: “People are often rude about the owners of fat dogs, blaming them for not properly managing their dogs’ diet and exercise. But we’ve shown that Labradors with this genetic mutation are looking for food all the time, trying to increase their energy intake. It’s very difficult to keep these dogs slim, but it can be done.”

̽��ֱ��researchers say owners can keep their retrievers distracted from this constant hunger by spreading out each daily food ration, for example by using puzzle feeders or scattering the food around the garden so it takes longer to eat.

In the study, 87 adult pet Labrador dogs - all a healthy weight or moderately overweight - took part in several tests including the ‘sausage in a box’ test.

First, the dogs were given a can of dogfood every 20 minutes until they chose not to eat any more. All ate huge amounts of food, but the dogs with the POMC mutation didn’t eat more than those without it. This showed that they all feel full with a similar amount of food.

Next, on a different day, the dogs were fed a standard amount of breakfast. Exactly three hours later they were offered a sausage in a box and their behaviour was recorded. ̽��ֱ��box was made of clear plastic with a perforated lid, so the dogs could see and smell the sausage, but couldn’t eat it.

̽��ֱ��researchers found that dogs with the POMC mutation tried significantly harder to get the sausage from the box than dogs without it, indicating greater hunger.

̽��ֱ��dogs were then allowed to sleep in a special chamber that measured the gases they breathed out. This revealed that dogs with the POMC mutation burn around 25% fewer calories than dogs without it.

̽��ֱ��POMC gene and the brain pathway it affects are similar in dogs and humans. ̽��ֱ��new findings are consistent with reports of extreme hunger in humans with POMC mutations, who tend to become obese at an early age and develop a host of clinical problems as a result.

Drugs currently in development for human obesity, underactive sexual desire and certain skin conditions target this brain pathway, so understanding it fully is important.

A mutation in the POMC gene in dogs prevents production of two chemical messengers in the dog brain, beta-melanocyte stimulating hormone (β-MSH) and beta-endorphin, but does not affect production of a third, alpha-melanocyte stimulating hormone (α-MSH).

Further laboratory studies by the team suggest that β-MSH and beta-endorphin are important in determining hunger and moderating energy use, and their role is independent of the presence of α-MSH. This challenges the previous belief, based on research in rats, that early onset human obesity due to POMC mutations is caused only by a lack of α-MSH. Rats don’t produce beta-melanocyte stimulating hormone, but humans and dogs produce both α- and β-MSH.

̽��ֱ��research was funded by ̽��ֱ��Dogs Trust and Wellcome.

Reference: Dittmann, M T et al: ‘Low resting metabolic rate and increased hunger due to β-MSH and β-endorphin deletion in a canine model.’ Science Advances, March 2024. DOI: 10.1126/sciadv.adj3823

New research finds around a quarter of Labrador retriever dogs face a double-whammy of feeling hungry all the time and burning fewer calories due to a genetic mutation.

Labradors with this genetic mutation are looking for food all the time, trying to increase their energy intake. It’s very difficult to keep these dogs slim, but it can be done.

Eleanor Raffan

A quarter of Labradors are hard-wired for obesity

Jane Goodall

Labrador retriever dog

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Treating newly-diagnosed Crohn's patients with advanced therapy leads to dramatic improvements in outcomes

cjb250 — Thu, 22 Feb 2024 11:30:27 +0000

A large-scale clinical trial of treatment strategies for Crohn’s disease has shown that offering early advanced therapy to all patients straight after diagnosis can drastically improve outcomes, including by reducing the number of people requiring urgent abdominal surgery for treatment of their disease by ten-fold.

Researchers redesign future mRNA therapeutics to prevent potentially harmful immune responses

jg533 — Wed, 06 Dec 2023 16:02:31 +0000

mRNA - or ‘messenger ribonucleic acid’ - is the genetic material that tells cells in the body how to make a specific protein. Researchers from the Medical Research Council (MRC) Toxicology Unit have discovered that the cellular machinery that ‘reads’ mRNAs ‘slips’ when confronted with repeats of a chemical modification commonly found in mRNA therapeutics. In addition to the target protein, these slips lead to the production of ‘off-target’ proteins triggering an unintended immune response.

mRNA vaccines are considered game-changing. They have been used to control the COVID-19 pandemic and are already proposed to treat various cancers, cardiovascular, respiratory, and immunological diseases in the future.

This revolutionary class of therapeutics was made possible in part through the work of biochemist Katalin Karikó and immunologist Drew Weissman. They demonstrated that by adding chemical modifications to the bases – the building blocks of mRNA – the synthetic mRNAs could bypass some of our body’s immune defences allowing a therapeutic to enter the cell and exert its effects. This discovery led to their award of the Nobel Prize in Physiology and Medicine in 2023.

̽��ֱ��latest developments, led by biochemist Professor Anne Willis and immunologist Dr James Thaventhiran from the MRC Toxicology Unit at the ̽��ֱ�� of Cambridge, build upon previous advances to ensure the prevention of any safety issues linked with future mRNA-based therapeutics. Their report was published on 6 December in the journal Nature.

̽��ֱ��researchers identified that bases with a chemical modification called N1-methylpseudouridine – which are currently contained in mRNA therapies – are responsible for the ‘slips’ along the mRNA sequence.

In collaboration with researchers at the Universities of Kent, Oxford and Liverpool, the MRC Toxicology Unit team tested for evidence of the production of ‘off-target’ proteins in people who received the mRNA Pfizer vaccine against COVID-19. They found an unintended immune response occurred in one third of the 21 patients in the study who were vaccinated – but with no ill-effects, in keeping with the extensive safety data available on these COVID-19 vaccines.

̽��ֱ��team then redesigned mRNA sequences to avoid these ‘off-target’ effects, by correcting the error-prone genetic sequences in the synthetic mRNA. This produced the intended protein. Such design modifications can easily be applied to future mRNA vaccines to produce their desired effects while preventing hazardous and unintended immune responses.

“Research has shown beyond doubt that mRNA vaccination against COVID-19 is safe. Billions of doses of the Moderna and Pfizer mRNA vaccines have been safely delivered, saving lives worldwide,” said Dr James Thaventhiran from the MRC Toxicology Unit, joint senior author of the report.

He added: “We need to ensure that mRNA vaccines of the future are as reliable. Our demonstration of ‘slip-resistant’ mRNAs is a vital contribution to future safety of this medicine platform.”

“These new therapeutics hold much promise for the treatment of a wide range of diseases. As billions of pounds flow into the next set of mRNA treatments, it is essential that these therapeutics are designed to be free from unintended side-effects,” said Professor Anne Willis, Director of the MRC Toxicology Unit and joint senior author of the report.

Thaventhiran, who is also a practising clinician at Addenbrooke’s hospital, said: “We can remove the error-prone code from the mRNA in vaccines so the body will make the proteins we want for an immune response without inadvertently making other proteins as well. ̽��ֱ��safety concern for future mRNA medicines is that mis-directed immunity has huge potential to be harmful, so off-target immune responses should always be avoided.”

Willis added: “Our work presents both a concern and a solution for this new type of medicine, and result from crucial collaborations between researchers from different disciplines and backgrounds. These findings can be implemented rapidly to prevent any future safety problems arising and ensure that new mRNA therapies are as safe and effective as the COVID-19 vaccines.”

Using synthetic mRNA for therapeutic purposes is attractive because it is cheap to produce, so can address substantial health inequalities across the globe by making these medicines more accessible. Moreover, synthetic mRNAs can be changed rapidly – for example to create a new COVID-19 variant vaccine.

In the Moderna and Pfizer COVID-19 vaccines, synthetic mRNA is used to enable the body to make the spike protein from SARS-CoV-2. ̽��ֱ��body recognises the viral proteins generated by mRNA vaccines as foreign and generates protective immunity. This persists, and if the body is later exposed to the virus its immune cells can neutralise it before it can cause serious illness.

̽��ֱ��cell’s decoding machinery is called a ribosome. It ‘reads’ the genetic code of both natural and synthetic mRNAs to produce proteins. ̽��ֱ��precise positioning of the ribosome on the mRNA is essential to make the right proteins because the ribosome ‘reads’ the mRNA sequence three bases at a time. Those three bases determine what amino acid is added next into the protein chain. Therefore, even a tiny shift in the ribosome along the mRNA will massively distort the code and the resulting protein.

When the ribosome is confronted with a string of these modified bases called N1-methylpseudouridine in the mRNA, it slips around 10% of the time causing the mRNA to be misread and unintended proteins to be produced – enough to trigger an immune response. Removing these runs of N1-methylpseudouridine from the mRNAs prevents ‘off-target’ protein production.

This research was funded by the Medical Research Council and the Wellcome LEAP R3 programme, and supported by the NIHR Cambridge BRC.

Reference: Mulroney, T E et al: ‘(N)1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting.’ Nature, Dec 23. DOI: 10.1038/s41586-023-06800-3

Researchers have discovered that misreading of therapeutic mRNAs by the cell’s decoding machinery can cause an unintended immune response in the body. They have identified the sequence within the mRNA that causes this to occur and found a way to prevent ‘off-target’ immune responses to enable the safer design of future mRNA therapeutics.

As billions of pounds flow into the next set of mRNA treatments, it is essential that these therapeutics are designed to be free from unintended side-effects.

Anne Willis

Libre de droit/ Getty Images

Strand of mRNA

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Part IV: Celebrating the Cambridge Women Changing the World

jek67 — Thu, 30 Mar 2023 07:43:37 +0000

Part IV - ̽��ֱ��Finale: To mark International Women's Day and Women's History Month, the ̽��ֱ�� is delighted to shine a light on some of the incredible women living and working here at Cambridge.

Training a new breed of clinical triallist

skbf2 — Thu, 03 Feb 2022 11:48:27 +0000

Cambridge's Experimental Medicine Initiative, working with AstraZeneca and GSK, is training specialists who can work out at an earlier stage of clinical trials if a treatment is likely to succeed.

Llama ‘nanobodies’ could hold key to preventing deadly post-transplant infection

sc604 — Thu, 22 Jul 2021 09:07:34 +0000

Around four out of five people in the UK are thought to be infected with HCMV, and in developing countries this can be as high as 95%. For the majority of people, the virus remains dormant, hidden away inside white blood cells, where it can remain undisturbed and undetected for decades. If the virus reactivates in a healthy individual, it does not usually cause symptoms. However, for people who are immunocompromised – for example, transplant recipients who need to take immunosuppressant drugs to prevent organ rejection – HCMV reactivation can be devastating.

At present, there is no effective vaccine against HCMV, and anti-viral drugs often prove ineffective or have very serious side-effects.

Now, in a study published in Nature Communications, researchers at Vrije Universiteit Amsterdam in the Netherlands and at the ̽��ֱ�� of Cambridge have found a way to chase the virus from its hiding place using a special type of antibody known as a nanobody.

Nanobodies were first identified in camels and exist in all camelids – a family of animals that also includes dromedary, llamas and alpacas. Human antibodies consist of two heavy and two light chains of molecules, which together recognise and bind to markers on the surface of a cell or virus known as antigens. For this special class of camelid antibodies, however, only a single fragment of the antibody – often referred to as single domain antibody or nanobody – is sufficient to properly recognize antigens.

Dr Timo De Groof from Vrije Universiteit Amsterdam, the study’s joint first author, said: “As the name suggests, nanobodies are much smaller than regular antibodies, which make them perfectly suited for particular types of antigens and relatively easy to manufacture and adjust. That’s why they’re being hailed as having the potential to revolutionise antibody therapies.”

̽��ֱ��first nanobody has been approved and introduced onto the market by biopharmaceutical company Ablynx, while other nanobodies are already in clinical trials for diseases like rheumatoid arthritis and certain cancers. Now, the team in ̽��ֱ��Netherlands and the UK have developed nanobodies that target a specific virus protein (US28), one of the few elements detectable on the surface of a HCMV latently infected cell and a main driver of this latent state.

Dr Ian Groves from the Department of Medicine at the ̽��ֱ�� of Cambridge said: “Our team has shown that nanobodies derived from llamas have the potential to outwit human cytomegalovirus. This could be very important as the virus can cause life-threatening complications in people whose immune systems are not functioning properly.”

In laboratory experiments using blood infected with the virus, the team showed that the nanobody binds to the US28 protein and interrupts the signals established through the protein that help keep the virus in its dormant state. Once this control is broken, the local immune cells are able to 'see' that the cell is infected, enabling the host’s immune cells to hunt down and kill the virus, purging the latent reservoir and clearing the blood of the virus.

Dr Elizabeth Elder, joint first author, who carried out her work while at the ̽��ֱ�� of Cambridge, said: “ ̽��ֱ��beauty of this approach is that it reactivates the virus just enough to make it visible to the immune system, but not enough for it to do what a virus normally does – replicating and spreading. ̽��ֱ��virus is forced to put its head above the parapet where it can then be killed by the immune system.”

Professor Martine Smit, also from from the Vrije Universiteit Amsterdam, added: “We believe our approach could lead to a much-needed new type of treatment for reducing – and potentially even preventing – CMV infectious in patients eligible for organ and stem cell transplants.”

̽��ֱ��research was funded by the Dutch Research Council (NWO), Wellcome and the Medical Research Council, with support from the NIHR Cambridge Biomedical Research Centre.

Reference
De Groof TWM, Elder E, et al. Targeting the latent human cytomegalovirus reservoir for T-cell mediated killing with virus specific nanobodies. Nature Communications (2021). DOI: 10.1038/s41467-021-24608-5

Scientists have developed a ‘nanobody’ – a small fragment of a llama antibody – that is capable of chasing out human cytomegalovirus (HCMV) as it hides away from the immune system. This then enables immune cells to seek out and destroy this potentially deadly virus.

Our team has shown that nanobodies derived from llamas have the potential to outwit human cytomegalovirus

Ian Groves

Jessica Knowlden on Unsplash

Llamas

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Key mutations in Alpha variant enable SARS-CoV-2 to overcome evolutionary weak points

cjb250 — Tue, 29 Jun 2021 07:00:14 +0000

SARS-CoV-2 is a coronavirus, so named because spike proteins on its surface give it the appearance of a crown (‘corona’). ̽��ֱ��spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. ̽��ֱ��virus manipulates the host cell’s machinery to allow the virus to replicate and spread.

As SARS-CoV-2 divides and replicates, errors in its genetic makeup cause it to mutate. Some mutations make the virus more transmissible or more infectious, some help it evade the immune response, potentially making vaccines less effective, while others have little effect.

Towards the end of 2020, Cambridge scientists observed SARS-CoV-2 mutating in the case of an immunocompromised patient treated with convalescent plasma. In particular, they saw the emergence of a key mutation - the deletion of two amino acids, H69/V70, in the spike protein. This deletion was later found in B1.1.7, the variant that led to the UK being forced once again into strict lockdown in December (now referred to as the ‘Alpha variant’).

Now, in research published in the journal Cell Reports, researchers show that the deletion H69/V70 is present in more than 600,000 SARS-CoV-2 genome sequences worldwide, and has seen global expansion, particularly across much of Europe, Africa and Asia.

̽��ֱ��research was led by scientists at the ̽��ֱ�� of Cambridge, MRC- ̽��ֱ�� of Glasgow Centre for Virus Research, ̽��ֱ��Pirbright Institute, MRC Laboratory of Molecular Biology, and Vir Biotechnology.

Professor Ravi Gupta from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the ̽��ֱ�� of Cambridge, the study’s senior author, said: “Although we first saw this mutation in an immunocompromised patient and then in the Kent – now ‘Alpha’ – variant, when we looked at samples from around the world, we saw that this mutation has occurred and spread multiple times independently.”

Working under secure conditions, Professor Gupta and colleagues used a harmless form of the virus that displays SARS-CoV-2 spike proteins with the H69/V70 deletion to understand how the spike protein interacts with host cells and what makes this mutation so important.

When they tested this virus against blood sera taken from fifteen individuals who had recovered from infection, they found that the deletion did not allow the virus to ‘escape’ neutralising antibodies made after being vaccinated or after previous infection. Instead, the team found that the deletion makes the virus twice as infective – that is, at breaking into the host’s cells – as a virus that dominated global infections during the latter half of 2020. This was because virus particles carrying the deletion had a greater number of mature spike proteins on their surface. This allows the virus to then replicate efficiently even when it has other mutations that might otherwise hinder the virus.

“When viruses replicate, any mutations they acquire can act as a double-edged sword: a mutation that enables the virus to evade the immune system might, for example, affect how well it is able to replicate,” said Professor Gupta.

“What we saw with the H69/V70 deletion was that in some cases, the deletion helped the virus compensate for the negative effects that came with other mutations which allowed the virus to escape the immune response. In other words, the deletion allowed these variants to have their cake and eat it – they were both better at escaping immunity and more infectious.”

Dr Dalan Bailey from ̽��ֱ��Pirbright Institute, who co-led the research, added: “In evolutionary terms, when a virus develops a weakness, it can lead to its demise, but the H69/V70 deletion means that the virus is able to mutate further than it otherwise would. This is likely to explain why these deletions are now so widespread.”

Bo Meng from the Department of Medicine at the ̽��ֱ�� of Cambridge, first author on the paper, said: “Understanding the significance of key mutations is important because it enables us to predict how a new variant might behave in humans when it is first identified. This means we can implement public health and containment strategies early on.”

̽��ֱ��research was supported by Wellcome, the Medical Research Council, the Bill & Melinda Gates Foundation and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.

Reference
Meng, B, Kemp, SA, Papa, G, Datir R, Ferreira, IATM et al. Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role 1 in the Alpha variant B.1.1.7. Cell Reports; 8 June 2021; DOI: 10.1016/j.celrep.2021.109292

One of the key mutations seen in the ‘Alpha variant’ of SARS-CoV-2 – the deletion of two amino acids, H69/V70 – enables the virus to overcome cracks in its armour as it evolves, say an international team of scientists.

Understanding the significance of key mutations is important because it enables us to predict how a new variant might behave in humans when it is first identified. This means we can implement public health and containment strategies early on

Bo Meng

Kevin Grieve

Man walking past Stay Alert/Save Lives artwork

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Likelihood of severe and ‘long’ COVID may be established very early on following infection

cjb250 — Mon, 18 Jan 2021 12:39:36 +0000

Among the key findings, which have not yet been peer-reviewed, are:

Individuals who have asymptomatic or mild disease show a robust immune response early on during infection.
Patients requiring admission to hospital have impaired immune responses and systemic inflammation (that is, chronic inflammation that may affect several organs) from the time of symptom onset.
Persistent abnormalities in immune cells and a change in the body’s inflammatory response may contribute to ‘long COVID’.

̽��ֱ��immune response associated with COVID-19 is complex. Most people who get infected by SARS-CoV-2 mount a successful antiviral response, resulting in few if any symptoms. In a minority of patients, however, there is evidence that the immune system over-reacts, leading to a flood of immune cells (a ‘cytokine storm’) and to chronic inflammation and damage to multiple organs, often resulting in death.

To better understand the relationship between the immune response and COVID-19 symptoms, scientists at the ̽��ֱ�� of Cambridge and Addenbrooke’s Hospital, Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, have been recruiting individuals who test positive for SARS-CoV-2 to the COVID-19 cohort of the NIHR BioResource. These individuals range from asymptomatic healthcare workers in whom the virus was detected on routine screening, through to patients requiring assisted ventilation. ̽��ֱ��team take blood samples from patients over several months, as well as continuing to measure their symptoms.

In research published today, the team analysed samples from 207 COVID-19 patients with a range of disease severities taken at regular interviews over three months following the onset of symptoms. They compared the samples against those taken from 45 healthy controls.

Because of the urgent need to share information relating to the pandemic, the researchers have published their report on MedRXiv. It has not yet been peer-reviewed.

Professor Ken Smith, senior co-author and Director of the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), said: “ ̽��ֱ��NIHR BioResource has allowed us to address two important questions regarding SARS-CoV-2. Firstly, how does the very early immune response in patients who recovered from disease with few or no symptoms, compare with those who experienced severe disease? And secondly, for those patients who experience severe disease, how rapidly does their immune system recover and how might this relate to ‘long COVID’?”

Listen to Professor Ken Smith discuss the findings with the Naked Scientists

̽��ֱ��team found evidence of an early, robust adaptive immune response in those infected individuals whose disease was asymptomatic or mildly symptomatic. An adaptive immune response is where the immune system identifies an infection and then produces T cells, B cells and antibodies specific to the virus to fight back. These individuals produced the immune components in larger numbers than patients with more severe COVID-19 managed, and within the first week of infection – after which these numbers rapidly returned to normal. There was no evidence in these individuals of systemic inflammation that can lead to damage in multiple organs.

In patients requiring admission to hospital, the early adaptive immune response was delayed, and profound abnormalities in a number of white cell subsets were present. Also present in the first blood sample taken from these patients was evidence of increased inflammation, something not seen in those with asymptomatic or mild disease. This suggests that an abnormal inflammatory component to the immune response is present even around the time of diagnosis in individuals who progress to severe disease.

̽��ֱ��team found that key molecular signatures produced in response to inflammation were present in patients admitted to hospital. They say that these signatures could potentially be used to predict the severity of a patient’s disease, as well as correlating with their risk of COVID-19 associated death.

Dr Paul Lyons, senior co-author, also from CITIID, said: “Our evidence suggests that the journey to severe COVID-19 may be established immediately after infection, or at the latest around the time that they begin to show symptoms. This finding could have major implications as to how the disease needs to be managed, as it suggests we need to begin treatment to stop the immune system causing damage very early on, and perhaps even pre-emptively in high risk groups screened and diagnosed before symptoms develop.”

̽��ֱ��researchers found no evidence of a relationship between viral load and progression to inflammatory disease. However, once inflammatory disease was established, viral load was associated with subsequent outcome.

̽��ֱ��study also provides clues to the biology underlying cases of ‘long COVID’ – where patients report experiencing symptoms of the disease, including fatigue, for several months after infection, even when they no longer test positive for SARS-CoV-2.

̽��ֱ��team found that profound alterations in many immune cell types often persisted for weeks or even months after SARS-CoV-2 infection, and these problems resolved themselves very differently depending on the type of immune cell. Some recover as systemic inflammation itself resolves, while others recover even in the face of persistent systemic inflammation. However, some cell populations remain markedly abnormal, or show only limited recovery, even after systemic inflammation has resolved and patients have been discharged from hospital.

Dr Laura Bergamaschi, the study’s first author, said: “It’s these populations of immune cells that still show abnormalities even when everything else seems to have resolved itself that might be of importance in long COVID. For some cell types, it may be that they are just slow to regenerate, but for others, including some types of T and B cells, it appears something is continuing to drive their activity. ̽��ֱ��more we understand about this, the more likely we will be able to better treat patients whose lives continue to be blighted by the after-effects of COVID-19.”

Professor John Bradley, Chief Investigator of the NIHR BioResource, said: “ ̽��ֱ��NIHR BioResource is a unique resource made possible by the strong links that exist in the UK between doctors and scientists in the NHS and at our universities. It’s because of collaborations such as this that we have learnt so much in such a short time about SARS-CoV-2.”

̽��ֱ��research was supported by CVC Capital Partners, the Evelyn Trust, UK Research & Innovation COVID Immunology Consortium, Addenbrooke’s Charitable Trust, the NIHR Cambridge Biomedical Research Centre and Wellcome.

Reference
Bergamaschi, L et al. Early immune pathology and persistent dysregulation characterise severe COVID-19. MedRXiV; 15 Jan 2021; DOI: 10.1101/2021.01.11.20248765

New research provides important insights into the role played by the immune system in preventing – and in some cases increasing the severity of – COVID-19 symptoms in patients. It also finds clues to why some people experience ‘long COVID’.

Our evidence suggests that the journey to severe COVID-19 may be established immediately after infection, or at the latest around the time that they begin to show symptoms

Paul Lyons

NIH Image Gallery

SARS-CoV-2 virus particles are shown emerging from the surface of cells cultured in the lab

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