Southampton researchers have shown that implementing point of care testing in hospitals to rapidly diagnose COVID-19 in patients is achievable and could be brought in ahead of a second wave of the disease. Management of the COVID-19 pandemic has been hampered by delays associated with the standard PCR test which requires samples to be sent to a laboratory, with results not being available for several hours to several days later. This leads to poor patient flow, as patients are held in assessment areas waiting for their results, and increases the risk of transmission if negative patients are exposed to patients with COVID-19. Fast, accurate results A team of researchers, led by Dr Tristan Clark from the from NIHR Southampton Biomedical Research Centre, used the QIAstat-Dx Respiratory SARS-CoV-2 Panel to test 500 patients admitted with COVID-19 symptoms during the first wave of the pandemic. A similar number of patients were also tested using the standard PCR laboratory test. The results, published in the journal Lancet Respiratory Medicine , showed that the point of care test was able to provide accurate results for patients in an average of time of around 100 minutes, compared to nearly 24 hours for patients tested with the laboratory test. As a result, patients tested with the point of care test could be moved on to the right ward for them nearly four times more quickly than those tested though laboratory PCR testing. Dr Clark, Associate Professor and Honorary Consultant in Infectious Diseases, said: “Our trial has shown that point of care testing for COVID-19 is feasible and is accurate and reliable. Point of care tests have major benefits over laboratory tests that would help hospitals control infections, allowing them to move patients who test positive to COVID-19 wards much faster.” Ready for winter The QIAstat-Dx test involves taking nasal and throat swabs from patients which are then mixed with a liquid transport medium to inactivate the virus. The liquid is then placed into a cartridge which is inserted into an analyser machine to providing a rapid ‘sample to answer’ process.It is one of several CE marked point-of-care tests available and was also shown in this trial to be more accurate than the laboratory PCR test that was most commonly used at the time. Patients who were diagnosed at point of care could also be enrolled into treatment trials, such as the national RECOVERY platform and the Southampton based Interferon Beta trial, much faster – on average two days faster than those diagnosed using laboratory tests. “These testing systems are available now and could be rolled out across NHS trusts in preparation for winter when the second wave of the virus is highly likely to occur,” Dr Clark concluded.

Southampton’s Professor Saul Faust is leading the UK trial of a new COVID-19 vaccine, aiming to recruit 6,000 volunteers from across the UK. The vaccine, designed by The Janssen Pharmaceutical Companies of Johnson & Johnson, uses a genetically modified common cold virus to train the immune system. Why do we need multiple vaccines? While recent preliminary results showed the Pfizer and BioNTech vaccine offered 90% protection, it has not yet been approved for use, and we still do not know how well it works across the population and for how long it protects. Many types of vaccine are likely to be needed to end the pandemic, with different approaches to creating vaccines being taken to understand what protects different people in different ways, and to offer alternative production and usage methods. Volunteers are still very much needed for vaccine trials to advance as many options as possible. Prof Saul Faust, director of the NIHR Southampton Clinical Research Facility and the Chief Investigator leading the trial, said: “Finding an effective vaccine with a good safety profile is a top priority in helping to protect us all more quickly against Covid-19. “While the news of a potential vaccine is tremendously exciting, our ambition in the scientific community is to ensure we leave no stone unturned in the search for a solution to help end this pandemic.” What will this trial involve? The phase 3 trial, co-funded by the UK government’s Vaccine Taskforce, is aiming to recruit 6,000 volunteers in the UK. The study will recruit up to 30,000 people worldwide. The Janssen vaccine uses a common cold virus that has been genetically modified to make it harmless and to look more like the Sars-CoV2 coronavirus at a molecular level. This should train the immune system to recognise and fight coronavirus. Half of the volunteers will be given two doses of the vaccine around two months apart, to test safety and effectiveness. Recruitment will end in March 2021 and the study will last for 12 months. Janssen already has one large scale trial of its vaccine in which volunteers get one dose - this trial will see if two gives a stronger and longer lasting immunity. If safe and effective, the UK government has agreed in principle for 30 million doses of the Janssen vaccine to be made available for the UK. Southampton is also playing a major role in a phase 3 trial of a vaccine designed by the University of Oxford and AstraZeneca, which showed promising early results, as well as earlier phase trials for two other vaccines led by Imperial College London and the University of Cambridge. Take part If you would like to take part in COVID-19 vaccine trials in the UK, please sign up to the NHS COVID-19 vaccine research registry. Anyone living in the UK cansign up online to take part in the trials through the NHS, giving permission for researchers to contact you if they think you’re a good fit. Once you sign up, you can withdraw at any time and request that your details be removed from the COVID-19 vaccine research registry. The process takes about 5 minutes to complete. The registry particularly needs volunteers who are most vulnerable to the effects of coronavirus, including frontline health and social care workers and people from Black, Asian and ethnic minority backgrounds.

The first COVID-19 patient has been treated with nebulised (inhaled) surfactant – a substance which makes it easier to breathe – as part of a new clinical trial led by University Hospital Southampton NHS Foundation Trust (UHS) and the University of Southampton (UoS). The first patient has been recruited to a study aiming to see if extra surfactant, the lung’s natural lubricant, could help prevent COVID-19 progressing and threatening patients’ lives. Making breathing easier Lung surfactant is a substance that reduces the work of breathing and prevents the lungs from collapsing. In some respiratory diseases and in patients that require ventilation this substance does not function normally. Use of surfactant is known to be safe and is already offered in other conditions, such as Neonatal Respiratory Distress Syndrome – where the lungs cannot provide the body with enough oxygen because of surfactant deficiency. Researchers in the COVSurf study, led by UHS and UoS and funded by the Bill and Melinda Gates Foundation, believe that poor surfactant function may be linked with deterioration in patients with moderate to severe COVID-19. Treating COVID-19 patients For the pilot study, researchers aim give up to 12 patients hospitalised with COVID-19 lung surfactant through use of the COVSurf Drug Delivery System, a process that involves a specially designed, ultrasonic nebuliser. This device vibrates rapidly to turn liquid into droplets of the ideal size for inhalation. Researchers will look at whether this method is feasible, and will begin to assess whether the procedure improves patient outcomes. The dose given to patients will be modified during the study based on how patients’ oxygen levels respond to the treatment as well as sophisticated mass spectrometry measures of surfactant levels available near the bedside within UHS. “The possibility that early surfactant replacement could help in Covid-19 is compelling. Surfactant is damaged in COVID -19, resulting in surfactant deficiency and acute respiratory distress syndrome,” comments Prof Howard Clark at University College London Hospitals NHS Foundation Trust, who recruited the first patient. “Surfactant therapy has been very effective in saving the lives of newborn preterm infants who require breathing assistance because of surfactant deficiency. We are looking forward to seeing whether this procedure is feasible, safe and effective in COVID-19 patients,” he adds. “We know that COVID-19 infects the lungs using receptors on the cells that produce surfactant, likely harming the cells and reducing surfactant function,” commented Prof Mike Grocott, lead for the COVSurf study. “Nebulised surfactant therapy is an exciting and promising candidate treatment for patients with COVID-19 who are requiring intensive care.”

There are literally not enough fish in the sea when it comes to recommended daily intake of omega-3 fatty acids. New research has shown that seed oil from genetically modified camelina plants is as good as fish oil at increasing two key types of omega-3 in the blood, pointing the way to a sustainable alternative source. A slippery problem Omega-3 fatty acids are a diverse group of fats that are important for health, which our body can’t make and must get them instead from food. Some omega-3 fatty acids, namely eiosapentaenoicacid (EPA) and docosahexaenoic acid (DHA) are vital parts of our cell membranes where they influence the activities of proteins such as hormone receptors and are the starting material for making substances that control the immune system. The UK government has made recommendations for daily intake of EPA and DHA to maintain health; consume two portions of fish per week, one of which should be oily. Oily fish such as salmon, mackerel and sardines are the main source of EPA and DHA, together with smaller amounts in meat and dairy products. However, most UK adults only consume about half the recommended amount of oily fish, while those who exclude animal-derived foods from their diet have intakes close to zero. EPA and DHA intakes in children are about 10% of recommended levels. The poor adherence to recommendations for EPA and DHA intakes is due to dislike of the taste of oily fish, the cost of oily fish and concerns about contamination with environmental pollutants. Moreover, global fish stocks can only provide 16% of the world population’s omega 3 needs. Overall, there is a clear need for sustainable and scalable alternatives that are broadly acceptable across the population. Plants not the answer – until now Plants are another source of omega-3, however they provide it in a form known as alpha-linolenic acid (ALA) which can be used to a very limited extent by the body to make EPA and DHA. This has been shown to be an inadequate alternative to consuming EPA and DHA. Now a study, led by Professor Graham Burdge in collaboration with Professor Johnathan Napier at the Rothamsted Research Institute, and published in The British Journal of Nutrition, has found that the seed oil from genetically modified strain of Camelina sativa can directly substitute for fish oil as a source of EPA and DHA in the human diet. Production of this modified camelina plant could easily be scaled up, with no greater impact on the environment than any other oil seed crop, to meet the health needs of the entire population – including vegans, vegetarians and those who choose not to eat oily fish. By reducing pressure on fishing stocks it could also help protect the marine environment. What did the study find? The researcher conducted two studies. The first showed absorption of EPA and DHA from a single meal was as good if they were provided by camelina oil and when consumed in fish oil. In the second study, thirty-one healthy participants were randomly assigned to two groups, with the first group taking a fish oil supplement daily for eight weeks and the second group taking oil from modified camelina. They then had a six week ‘wash out’ period where they took neither supplement, before the two groups swapped to take the other oil, again daily for eight weeks. For both groups, their daily dose was calculated so that their omega-3 intake matched the amount recommended by UK health guidelines (450mg EPA and DHA per day in adults). The researchers found comparable amounts of omega-3s EPA and DHA in the blood of participants who had taken the fish oil and those who had taken the camelina oil. Professor Graham Burdge said: “These results show that seed oil from camelina plants that have been genetically modified to produce these two omega-3 fatty acids, could provide a sustainable plant-based alternative source of EPA and DHA that is as good as fish oil. “This work was entirely supported by British tax payers through the Biotechnology and Biological Sciences Research Council with no commercial input. Moreover, this globally unique plant could be a world beating novel crop for British farmers.”

The people of Southampton made a major contribution to data showing that a University of Oxford-developed COVID-19 vaccine could protect between 70% and 90% of the population, depending on the dose pattern used. The trial shows the University of Oxford and AstraZeneca vaccine has an average effectiveness of 70%. However, this is the average of results from two different dosing patterns – two higher dose injections showing 62% protection, and one lower-dose jab followed later by a higher dose providing 90% protection. Importantly, no one who received the COVID-19 vaccine at any dose developed severe COVID-19 symptoms, indicating that even for those who it doesn’t protect from infection, it might protect from the diseases’ damaging effects. The initial data also shows that the vaccine may have a role in stopping transmission of COVID by people without symptoms. The Oxford-AstraZeneca vaccine is also relatively cheap to produce in large quantities, and can be stored at fridge temperature, which makes it easier to distribute across the NHS and globally. The UK government has pre-ordered 100 million doses of the Oxford-AstraZeneca vaccine, enough to immunise 50 million people, or even more if the schedule using the lower dose first is recommended by the Medicines and Healthcare Regulatory Agency (MHRA). Southampton volunteers vital More than 20,000 volunteers were involved in the trial - half in the UK, half in Brazil. In Southampton, 240 of the city’s over 70s stepped up to provide all of the data showing the initial safety and effectiveness of the vaccine in their higher-risk age group, as reported in the medical journal The Lancet last week. Overall, in the large phase 3 trial there were 30 cases of COVID-19 in people who had two doses of the vaccine, and 101 cases in people who received the meningitis vaccine injection (the control). “We want to say a massive thank you to the people of Southampton and Hampshire who have joined us and contributed to a way out of this pandemic, despite the anxieties and uncertainties of the situation,” comments Professor Saul Faust, trial lead for Southampton and Director of NIHR Southampton Clinical Research Facility. “Each time we have opened a new phase of the Oxford Vaccine trial or trials of other COVID vaccines, we have been overwhelmed by the response – it’s been fantastic for us in the NHS to work with our city and region to find a way out.” “We still need to do further work on this and other vaccines in development, to give us the best range of vaccination options, and the best ways of using each vaccine,” he adds. “I’d encourage everybody to sign up to the NHS vaccine registry to hear about opportunities to be part of this research – as this trial shows, it’s not as simple as testing different vaccines – how and in who each one is used can make a big difference.” You can sign up to the NHS vaccine registry to be contacted about taking part in COVID-19 vaccine studies happening in the UK, including those in Southampton. How does the vaccine work? The vaccine, known as ChAdOx1 nCoV-19, is made from a weakened version of a common cold virus (adenovirus) from chimpanzees that has been genetically changed so that it is impossible for it to grow in humans. This has been combined with genes that make ‘spike protein’ from the COVID-19 virus (SARS-CoV-2), which plays an essential role in the infection pathway of the virus. The intention is that the immune system responds to the vaccine as if it is coronavirus, providing future protection if the person later catches the virus. “These findings show that we have an effective vaccine that will save many lives,” said Professor Andrew Pollard, Chief Investigator of the Oxford Vaccine Trial at Oxford. “Excitingly, we’ve found that one of our dosing regimens may be around 90% effective and if this dosing regime is used, more people could be vaccinated with planned vaccine supply.” Today’s announcement is only possible thanks to the many volunteers in our trial, and the hard working and talented team of researchers based around the world.”

Southampton-led research has shown that implementing point-of-care testing in hospitals to diagnose influenza (flu) can lead to better treatment and faster recovery for patients. The researchers are now calling for routine use of these tests to become standard for patients admitted with acute respiratory symptoms during the influenza season. Why use point-of-care tests? The influenza virus causes seasonal epidemics of acute illnesses every winter. Adults who are admitted to hospitals are often taken to critical care wards and between 3% to 15% die in hospital. Diagnosis of influenza in hospitals takes time, due to the turnaround time of the standard PCR test, which requires samples to be sent to a laboratory, leading to later antiviral treatment and isolation facility use. Molecular point-of-care tests (POCT) are highly accurate and can provide results in less than one hour, but there has been limited assessment of their effectiveness in terms of improving recovery for patients in clinical settings. Faster diagnosis of flu In this new study, a team of researchers from University of Southampton and University Hospital Southampton randomised patients admitted with acute respiratory symptoms to receive point-of-care testing using the FilmArray Respiratory Panel 2 or routine clinical care – where testing was at the discretion of the clinical teams – and used stranded laboratory testing. Over two concurrent influenza seasons around 600 patients were enrolled in total, with just over 300 in each group. Patients in the point-of-care group had a nose and throat swab performed and immediately tested on the FilmArray instrument located in the acute area, with the results communicated to clinical teams as soon as available. The findings, published in the journal Lancet Respiratory Medicine, showed that patients tested routinely with the point-of-care test received their result much more rapidly and were much more likely to be correctly diagnosed with influenza. 100% of the patients who had influenza in this group were correctly diagnosed compared to just 62% of patients with influenza who received routine care. Those that remained undiagnosed in the routine care group did not receive antivirals and were not nursed in single room accommodation, meaning that they were much more likely to pass influenza on to other patients. The results for the patients in the point-of-care group were available within one hour, meaning those with confirmed influenza received the necessary antiviral treatment faster than those in the routine care group whose results took almost a day to come back. In addition, those in the point-of-care testing group recovered faster and were less likely to deteriorate, compared to those in the standard care arm. The trial was led by Dr Tristan Clark, Associate Professor and Honorary Consultant in Infectious Diseases at the University of Southampton and University Hospital Southampton. He said, “Our trial has shown that routine molecular POCT for influenza in hospitals leads to improvements in influenza detection, antiviral use, isolation facility use and recovery compared with the current standard of care. “We feel that this is practice changing and that guidelines should change as a result. Obviously the current COVID-19 pandemic makes the current situation more complex, but the broad principles of needing to test at the point-of-care are applicable to both conditions.”

The interim analysis data for the Oxford-AstraZeneca vaccine trial for COVID-19 has been published in The Lancet, following a press release a couple of weeks ago. Dosing differences The results show that the ChAdOx1 nCoV-19 vaccine is safe and effective, with an average effectiveness of 70%. This is the average of results from two different dosing schedules – two higher dose injections showing 62% protection, and one lower dose jab followed later by a higher dose which provided 90% protection. That surprising result was based on data from only 1,367 of the 11,636 participants (7548 in the UK, 4088 in Brazil), after a manufacturing issue resulted in a batch of lower strength doses. The Medicines and Healthcare products Regulatory Authority agreed this batch should still be used in the trial, yielding what appears to be a lucky find. Those small numbers mean that although the published data indicates that the vaccine is safe and effective, it’s hard to draw firm conclusions about the seemingly more effective dosing schedule. This is especially true for over 55s, none of whom were given that dose - although earlier trial results reported in The Lancet showed the vaccine is safe and produces strong immune responses in older people, thanks to 240 over 70s in Southampton who provided the data for this higher-risk age group. What happens next? The Medicines and Healthcare Regulatory Agency (MHRA) are considering whether to approve the vaccine - a key regulatory step before it can be distributed and given to patients. The UK government has pre-ordered 100 million doses of the Oxford-AstraZeneca vaccine, enough to immunise 50 million people - or more if the schedule using the lower dose first is recommended. The vaccine, known as ChAdOx1 nCoV-19, is made from a weakened version of a common cold virus (adenovirus) from chimpanzees that has been genetically changed so that it is impossible for it to grow in humans.This has been combined with genes that make ‘spike protein’ from the COVID-19 virus (SARS-CoV-2), which plays an essential role in the infection pathway of the virus. It is relatively cheap to produce in large quantities, and can be stored at fridge temperature, which makes it easier to distribute across the NHS and globally. Work on COVID-19 vaccines continues to be of great importance, to give the best range of options and the best ways of using each vaccine. You can sign up to the NHS vaccine registry to be contacted about taking part in COVID-19 vaccine studies in the UK, including in Southampton

Professor Keith Godfrey, Dr Katrina Cathie and Dr Nisreen Alwan have all been awarded MBEs in the Queen’s New Year Honours list for 2021 in recognition of their efforts to tackle COVID-19. Professor Godfrey – established Southampton saliva testing programme Professor Keith Godfrey’s drive and leadership in piloting effective, regular mass testing for COVID-19 was recognised in the honours, underscoring the importance of Southampton’s testing programme. That programme pioneered weekly at-home self- sampling for COVID-19 using saliva, rather than uncomfortable and challenging nose and throat swabbing, helping educational isettings in the city identify and manage infections. I also demonstrated the reliability of the RT-LAMP testing technology, cheaper and faster than RT-PCR, and seamless integration of laboratory and NHS data systems to feedback of laboratory test results to participants by text and in national test and trace systems. This work is now focussed on how the approach might be scaled up to a sub-regional level. April 2020 Keith brought together a unique team to develop a testing solution that would help ease restrictions. That team included experts in public health, social science, behavioural science, clinical data systems, education and infectious disease molecular biology, plus programme management, communications and legal professionals. A unique partnership that spanned the Hampshire and Isle of Wight region, the programme was centred on a collaboration between University of Southampton and Southampton City Council. Together they have piloted the approach in employer and educational settings, providing vital learning for the nation that has already been applied in cities and testing approaches across the UK. “It is a huge honour to be recognised in this way, but this really is a tribute to a truly dedicated team who have worked tirelessly to mitigate the worst effects of the COVID epidemic on the most vulnerable in society,” comments Professor Godfrey , nutrition theme lead for the NIHR Southampton Biomedical Research Centre, professor of epidemiology and human development and honorary consultant. “The team has formed a strong partnership between the University of Southampton, the Aspire Community Trust, Southampton City Council, the Animal and Plant Health Agency in Weybridge and the NHS. Working together, we have made enormous progress in developing saliva-based testing to reduce the risk of infection transmission in educational and other settings in Southampton, to give confidence to students, staff, parents and local communities, and to inform national policy and coronavirus control measures elsewhere across the country.” Dr Nisreen Alwan – weekly testing proposal and Long COVID awareness Dr Nisreen Alwan’ leading role in a national group of senior public health experts and epidemiologists was the critical spark for the Southampton testing programme. March and April 2020 saw Nisreen and that group producing multiple outputs and open letters to the government on the UK pandemic response, including a proposal for COVID-19 universal weekly testing, that stimulated efforts to find mass testing solutions for controlling the pandemic. Nisreen’s MBE for services to medicine and public health during the pandemic recognises both this pivotal role, and also her tireless work on Long COVID. It follows her inclusion in the BBC top 100 Women list in November 2020. Her persistent scientific and public advocacy has been instrumental in the recognition of Long COVID on a national and international level. Throughout the pandemic, Nisreen has also highlighted the role of social factors like race, gender and class in the pandemic’s impact on individuals and different groups, and the importance of addressing ethnic and socioeconomic inequalities. Her frequent calls for further resources and investigations into the effects of Long COVID have been a prevalent theme of her engagements on social media, mainstream media, webinars and journal articles. “I couldn’t believe it when I saw the email notifying me of the MBE,” said Dr Alwan. “I am so honoured and grateful to be nominated and feel a huge responsibility to continue contributing to society in a meaningful way. A big thank you to all those who supported me during this difficult year. Through the work I did, I connected with so many kind, dedicated, and wise people. This gives me hope and energy to always seek positive change”. Dr Katrina Cathie – for services to paediatrics and the COVID-19 response At the start of the pandemic, consultant paediatrician Dr Cathie volunteered to leave her research duties to help patients and colleagues in clinical areas. She later helped oversee the COVID vaccine study at University of Southampton in collaboration with University of Oxford, as well as becoming a lead principal investigator for the Janssen COVID-19 vaccine trial. "I am hugely humbled and honoured to receive this award,” said Dr Cathie. “I am thankful for family, friends and colleagues who support me and I am grateful to work in research and clinical teams with others who go above and beyond on a daily basis and without whom, I wouldn't be able to do my job."

A shadow over the promising inhaled interferon beta COVID-19 therapy has been cleared with the discovery that although it appears to increase levels of ACE2 protein – coronavirus’ key entry point into nose and lung cells – it predominantly increases levels of a short version of that protein, which the virus cannot bind to. The virus that causes COVID-19, known as SARS-CoV-2, enters nose and lung cells through binding of its spike protein to the cell surface protein angiotensin converting enzyme 2 (ACE2). Now a new, short, form of ACE2 has been identified by Professor Jane Lucas, Professor Donna Davies, Dr Gabrielle Wheway and Dr Vito Mennella at University Hospital Southampton NHS Foundation Trust and the University of Southampton. The study, published in Nature Genetics, shows that as well as the longer form of ACE2 used by SARS-CoV-2, a shorter form of ACE2 exists that lacks the SARS-CoV-2 binding site. Supporting interferon treatment Naturally occurring antiviral proteins called interferons have shown promise in treating COVID-19. However, previous studies have shown that interferons increase levels of ACE2 – casting doubts over the potential for such treatments, with the possibility that increased ACE2 could see these drugs actually worsen COVID-19 impacts. But this latest research shows that it is predominantly the short ACE2, which lacks the viral binding site, that is increased in response to interferons. Since levels of the longer form of ACE2 remain unchanged, interferons do not appear to boost entry points for the virus, supporting their use in treating COVID-19 patients. This helps to explain the hugely promising results for a trial of an inhaled interferon beta treatment for COVID-19 patients, developed in Southampton by a team led by Professor Tom Wilkinson. Improving COVID-19 knowledge This research gives a new insight into this short form of ACE2, and shows how it has a very different role to the longer form of ACE2 that acts as entry point for SARS-CoV-2. Short ACE2 lacks the binding site for SARS-CoV-2, so it cannot be used as an entry point for the virus. Instead, its regulation by interferons suggests it may be involved in the body’s anti-viral response. As the researchers showed that short ACE2 does not increase in response to SARS-CoV-2 infection, it is unlikely to be involved in the body’s immune response to COVID-19, but it did increase in response to another common respiratory virus. These results will enable researchers to distinguish between these two forms of ACE2, knowledge which could prove invaluable for developing more sophisticated treatments for COVID-19 patients. Professor Jane Lucas, Professor of Paediatric Respiratory Medicine at the University of Southampton and Honorary Consultant Paediatric Respiratory Medicine at University Hospital Southampton and one of the lead authors for the study, said: “We were excited to discover a new form of ACE2, and became even more interested when we realised that may be protective against SARS-CoV-2 in the airways rather than an entry site for infection. We believe this may have important implications for managing COVID-19 infection and we are starting further studies to investigate this further.”

Southampton doctors are calling on the city and region’s adults to join trials of a vaccine using tried and tested technology to tackle the virus from yet another angle. These early phase 1 and 2 studies are testing how well the UK-developed vaccine triggers the body’s immune defences against coronavirus, and its safety in 150 healthy adults aged 18-55. Southampton doctors are asking the city and region to help out and sign up via the link at www.UKCovid19study.com. Why do we need more vaccines? “It’s vital we continue to test new vaccines as they become available. As the new variants have shown, coronavirus keeps moving the goalposts and it’s unlikely that there will be a single solution that protects everyone and gets us out of this,” comments Professor Saul Faust from the National Institute of Health Research and the University of Southampton. “Different vaccines work in different ways, and we need the public’s help to understand how well each one protects us and prevents transmission, particularly which ones are most appropriate for different groups of people. Searching ‘covid19 study registry' and signing up is a positive step anyone can take to help the NHS tackle the virus and get us all out of the pandemic,” adds Prof Faust. Proven technology Made by biotech company Valneva, this latest vaccine uses a proven technology already used in existing vaccines used for prevention of diseases such as flu, Japanese encephalitis, tick borne encephalitis, polio, and rabies. In doing so, it takes a completely different approach to the recently licensed Oxford-AstraZeneca, Pfizer and Moderna vaccines, potentially providing additional resilience against new variants. If successful, these early trials will pave the way for larger trials involving more than 4,000 volunteers UK-wide, testing two doses of the vaccine in in those aged 18-65 and the over 65s. Early access to 60 million doses of this vaccine, subject to successful trials, has been secured by the UK Government, with up to 250 million vaccine doses to be supplied worldwide. This is the fifth NIHR-supported vaccine to enter clinical trials in the UK, alongside Oxford/AstraZeneca, Imperial College London, Novavax and Janssen, whose studies are currently ongoing. Sign up to help Some of the volunteers taking part in these latest clinical trials came through from the NHS COVID-19 Vaccine Research Registry, which enables the UK public to support the national effort to speed up vaccine research. The Registry was launched by the UK government in partnership with the NIHR, NHS Digital, the Scottish and Welsh governments and the Northern Ireland Executive earlier this year. Over 365,000 people have already signed up to the Registry, giving their permission to be contacted about taking part in vaccine research, but more volunteers are still needed. You can sign up as a volunteer for this vaccine trial at: www.UKCovid19study.com

Risk of death in critically ill patients is reduced by two anti-inflammatory drugs, according to new results from a global trial involving Southampton researchers. Two drugs – tocilizumab and sarilumab – have been shown to cut relative risk of death by almost a quarter in adult patients seriously ill with COVID-19. Critically ill COVID-19 patients treated with the drugs, which are used to treat inflammatory conditions such as rheumatoid arthritis, also left intensive care units (ICUs) up to 10 days earlier. The research was part of the international REMAP-CAP study, for which Dr Ahilanandan Dushianthan and the critical care research nursing team are recruiting COVID-19 patients admitted to intensive care at University Hospital Southampton. Saving lives Adult patients with COVID-19 were recruited within 24 hours of starting organ support in the intensive care unit (ICU). They were then randomly assigned to receive either tocilizumab (8mg/kg), sarilumab (400mg) or standard care (control group). Both drugs reduced the relative risk of death by 24% over standard care, which saw the majority of patients treated with dexamethasone, one of the few treatments already established to lower mortality in COVID-19 – indicating additive benefits of these latest drugs. Patients who received the drugs also left intensive care between 7 to 10 days earlier on average, meaning that their use could help reduce pressures on hospitals over the coming weeks and months. “As a result of this work, most of our enrolled patients had the opportunity to receive multiple potential treatment strategies, including anti-IL 6, which may partly explain the reason for our excellent clinical outcomes,” comments Dr Ahilanandan Dushianthan, ICU consultant in respiratory medicine and Southampton lead for REMAP-CAP. “It is a privilege to be part of a positive ICU clinical study, particularly during this challenging time. However, we need to be patient until all the results are published in a peer reviewed journal, while results are also expected from the RECOVERY trial. “This is a testing time for all of us, and I want to thank Kim Golder (REMAP-CAP lead) and the UHS critical care research nursing team, who are an integral part of our clinical team managing critically-ill COVID-19 patients,” he adds. “Their tireless efforts have seen enrolled 85 patients so far, making us one of the highest recruiting centres in the UK. This is a mammoth achievement for any clinical study, and I can't remember if we have ever managed to enrol this many participants into an ICU clinical trial.” Reducing dangerous inflammation An excessive inflammatory response to COVID-19 infection is seen in many critically ill patients, which if left untreated can damage the lungs and other organs. Interleukin-6 is central to this inflammatory response to infection. Tocilizumab and sarilumab bind to and block the interleukin-6 receptor, dampening down this excessive inflammation. Previous studies that included less severely affected COVID-19 patients did not show such clear effects, suggesting these drugs are most beneficial for ICU patients seriously ill with COVID-19.

COVID-19 therapy inhaled interferon beta has entered into large-scale international trials, following early phase results indicating it could prevent patients’ decline, cutting ICU usage and improving recovery times. The first patient has received a treatment developed by University of Southampton spin-out Synairgen that could prevent patients hospitalised with COVID-19 from getting worse, in a new large-scale trial. The treatment – a fine mist of the protein interferon beta breathed deep into the lungs – is thought to help prevent COVID-19 getting worse by boosting the lungs’ antiviral defences and preventing lung damage. In early stage trials, it reduced hospitalised COVID-19 patients’ odds of developing severe symptoms by up to 80%, avoiding intensive care and saw a doubling of those that were discharged in the two weeks following treatment. This larger phase 3 trial, led by Professor Tom Wilkinson, respiratory research theme lead of the NIHR Southampton Biomedical Research Centre in collaboration with Synairgen, will build on these early findings to involve more than 600 patients in 20 countries. Protecting hospital patients Alexandra Constantin, 34, was the first person to receive the treatment as part of this new trial, after she was admitted to the hospital with coronavirus on Monday. She received the treatment at Hull Royal Infirmary on Tuesday afternoon, where she was asked to breathe the drug deeply into her lungs using a nebuliser – a machine that converts it into a fine mist. A course of treatment with the new drug could cost around £2,000, which is not that expensive for a hospital treatment. If successful, the researchers expect it could be approved for use in the summer. “We need treatments as well as vaccines to fight highly pathogenic viruses such as SARS-CoV-2,” commented Richard Marsden, CEO of Synairgen. “ “Development of treatments like ours will remain necessary in cases where vaccines are not effective, for those who do not get vaccinated, and in case the virus mutates to the point where vaccines become less effective. “We believe this trial presents an opportunity for a significant UK scientific breakthrough and, if given the right support, our drug could rapidly assist with the global crisis.” Promising early results Early findings suggest the treatment could cut the odds of a COVID-19 patient developing severe disease - such as requiring ventilation - by almost 80%. The research was led by Professor Tom Wilkinson in collaboration with Synairgen, a respiratory drug discovery and development company founded by the University of Southampton professors Stephen Holgate, Donna Davies and Ratko Djukanovic. The results of their previous phase 2 trial, involving 100 COVID-19 patients from nine UK hospitals, found those who received the drug had reduced breathlessness and were more than twice as likely to recover to the point where their everyday activities were not hindered by the illness. They have also shown that the drug can stimulate an immune response, and that patients with asthma and other chronic lung conditions can comfortably tolerate the treatment. Immune boost Interferon beta is a protein that occurs naturally in the body with antiviral properties. It is commonly given as an injection in the treatment of multiple sclerosis. There is evidence that older people and people with some chronic health conditions have poorer interferon beta responses, and also that the virus that causes COVID-19 suppresses interferon beta production by cells in the body. It is thought that breathing it in as a fine mist boosts the lung’s immune response – enhancing protection, accelerating patients’ recovery and countering the impact of the virus. Synairgen is also running an ongoing Phase II trial of inhaled interferon beta in non-hospitalised ‘at risk’ patients. For more information and to take part, visit www.covidtrialathome.com.