Volunteers from Southampton, Portsmouth and Bournemouth will soon be able to receive a third ‘booster’ COVID-19 vaccine through a new clinical trial launching this week, led by Professor Saul Faust at University Hospital Southampton. The Cov-Boost study, backed by £19.3 million of government funding through the Vaccines Taskforce, will be run at University Hospital Southampton, University Hospitals Dorset and the Portsmouth Research Hub, and is being led by University Hospital Southampton. First COVID-19 booster trial in the world It will be the first in the world to provide vital data on the impact of a third dose on patients’ immune responses. The study will give scientists from around the world and the experts behind the UK’s COVID-19 vaccination programme a better idea of how effective a booster of each vaccine is in protecting the individual from the virus. The initial findings, expected in September, will help inform decisions by the Joint Committee on Vaccination and Immunisation (JCVI) on any potential booster programme from autumn this year, ensuring the country’s most vulnerable are given the strongest possible protection over the winter period. Trialling seven vaccines as potential boosters The trial will look at seven different COVID-19 vaccines as potential boosters, given at least 10 to 12 weeks after a second dose as part of the ongoing vaccination programme. One booster will be provided to each volunteer and could be a different brand to the one they were originally vaccinated with. Vaccines being trialled include Oxford/AstraZeneca, Pfizer/BioNTech, Moderna, Novavax, Valneva, Janssen and Curevac, as well as a control group. The trial has received ethics approval by the NHS Research Ethics Committee, as well as approval from the Medicines and Healthcare products Regulatory Agency. Taking part The study will be recruiting participants through the NHS COVID-19 Vaccine Research Registry, with vaccinations set to start from the beginning of June. Participants will be adults aged 30 years or older and will include those immunised early on in the vaccination programme - for example, adults aged 75 and over or health and care workers. The study will take place at 16 NIHR-supported sites across the UK, and will include a total of 2,886 patients. All participants will be monitored throughout the study for any potential side effects and will have bloods taken to measure their immune responses at days 28, 84, 308 and 365, with a small number having additional blood tests at other times. All sites will have an electronic diary for all participants that will send alerts to the team in real time if needed and a 24-hour emergency phone to a doctor on the study, who can provide further clinical advice. All the trial sites are working on ways of including people in research from a wide variety of backgrounds and individuals from ethnic minorities are encouraged to apply. Those interested can find out more on Twitter @CovBoost and the website covboost.org. Preparing the UK booster programme The government is preparing for a potential booster programme based on clinical need and will publish further details in due course. The final policy will be informed by advice from the JCVI and take into account the results of clinical trials. Professor Saul Faust, Chief Investigator and Director of NIHR Southampton Clinical Research Facility, said: “This trial will give the Joint Committee on Vaccination and Immunisation the important data to inform their recommendations of how to protect the population against any future wave. “It is fantastic that so many people across the country have taken part in vaccine trials up to now so that we can be in a position to study the effects of boosters, and we hope that as many people as possible over the age of 30 who received their first dose early in the NHS programme will be able to take part.”

Southampton nurses part of the national COVID-NURSE study will assess new approaches to caring for COVID-19 patients, to inform new guidelines. Evidence-based nursing COVID-19 has presented huge care challenges for nurses, from communicating with patients while wearing personal protective equipment (PPE), to supporting their mental and emotional wellbeing in the absence of friends and relatives. Yet they have also risen to these challenges, coming up with innovative solutions that mean they can continue to provide the best care possible. The COVID-NURSE study aims to assess these developments, identifying which approaches are most effective to inform best practice guidance. This will allow nurses to care for those with COVID-19 using tried and tested innovations that have been shown to be effective. Southampton’s nursing innovations Over the next few weeks a COVID-19 nursing team at University Hospital Southampton will assess various approaches that could help to improve the patients’ health and wellbeing during their stay. That includes the addition of a “6th Vital Sign” to the remaining 5 (respiration rate, oxygen saturation, blood pressure, pulse rate and temperature). This will be focused on the monitoring of the patients’ mental health and well-being. Three main questions will be asked: “how are you feeling today?”, “why are you feeling like that?” and “what can we do to support you?” The nurses involved in the study believe that building this into their routine could be a ‘game changer’ moving forward in patient care. An assessment of discussions helping assess and support the nursing team’s mental health as part of daily team meetings is also part of the study, reflecting the impact of COVID care on nursing teams and its importance to morale. Elsewhere, building communication into daily care routines is the focus of a nominated family link nurse innovation. They will take responsibility in the team for establishing contact between patients and their loved ones, and making sure patients are given the option of a virtual visit every breakfast and lunch time. Again, there are staff-focussed communication innovations on test as well, including a new section in medical notes for communication between medical/nursing staff and relatives, allowing them to quickly refer back to previous conversations and keep tracks of updates.

ACCORD – a Phase 2, clinical trial platform designed to rapidly test candidate drugs for the treatment of COVID-19 – has completed patient recruitment for the first of its arms. The ongoing study is delivered in collaboration with the Medicines Evaluation Unit in Manchester and NHS hospital sites across the UK, supported by the NIHR. ACCORD is led by Professor Tom Wilkinson at the NIHR Southampton Biomedical Research Centre. ACCORD’s work evaluating new candidate drugs for large scale trials is vital, with only limited treatment options for those who are hospitalised with COVID-19. Despite vaccine programmes helping to reduce COVID-19 cases and incidence of severe COVID-19, new treatments will remain critical to improving outcomes for hospitalised patients and reducing pressure on intensive care units. Analysis of the full dataset from ACCORD is expected to be completed in the next few months following completion of patient recruitment in the additional two arms.

Southampton is set to be part of a trial aiming to infect and closely monitor up to 90 low-risk healthy volunteers to better understand the disease and speed up vaccine development. This ‘human challenge’ trial is the world’s first for COVID-19 and has been approved by the UK’s clinical trials regulatory body. Due to start in a few weeks, it has been designed and planned by a consortium of clinical investigators, including the Director of the NIHR Southampton Biomedical Research Centre, Professor Robert Read. Studying coronavirus infection This initial trial aims to establish the smallest amount of virus needed to cause infection, but it is hoped that further trials will follow. It will monitor up to 90 healthy 18 to 30 year olds, who are at low risk of developing complications, after they are given the virus in a safe, controlled environment. Following the initial screening, the participants will go into quarantine at the Royal Free hospital in London, and two days later will be given the virus via drops into their nose. They will then be monitored 24 hours a day for a minimum of 14 days, with daily nose swabs and blood samples. The researchers will continue to follow up with them for a year to check for any long-lasting symptoms, with a total of around £4,500 compensation offered for this time to cover expenses. The researchers hope that this initial trial will give a better understanding of the disease, including shedding of the virus, transmission, and how the body’s immune system responds to it. Developing vaccines faster “One of the important reasons for wanting to do this study is that it is the fastest way to evaluate novel vaccines,” said Professor Read. Falling rates of COVID-19, while an obvious cause for celebration, make it harder to conduct vaccine trials and mean they take longer. Human challenge trials would allow vaccine development and improvement to continue at pace, even with fewer cases as the virus is brought under control. Human challenge trials could also be valuable as a faster way to discover new or modified vaccines that are more effective against new variants, and likely to be useful for developing boosters. “A human challenge allows you to vaccinate volunteers and then infect them in a controlled way with the virus, to compare perhaps new vaccines with first-generation vaccines to provide information to the regulatory authorities so that they can understand the potential of novel vaccines head to head with the established vaccines that already exist,” adds Prof Read. Taking part The researchers are looking for healthy 18 to 30 year olds not previously exposed to the virus. If you are interested in taking part, please register your interest on the UK COVID Challenge website.

Southampton doctors are calling for volunteers over the age of 50 to take part in a study looking at the impact of varying the time between doses, and using different coronavirus vaccines for first and second doses. The trial will compare peoples’ immune response to booster injections at either 28 days or 12 weeks after their first dose. These intervals will be tested using the Oxford/AstraZeneca and Pfizer/BioNTech vaccines currently being rolled out across the NHS, and also in mixed dosing – using one vaccine for the first dose and the other for the second. “This trial will provide vital data for all our reassurance about the current NHS vaccine roll out, and for how we use COVID-19 vaccines in the future,” said Professor Saul Faust, Director of the NIHR Southampton CRF, who is leading the trial locally. Volunteers needed The study will be run in the NIHR Southampton Clinical Research Facility (CRF) at University Hospital Southampton, aiming to recruit 100 volunteers aged 50-years-old and above. They will join 700 others at seven further sites nationally in the study referred to as the COVID-19 Heterologous Prime Boost study, or ‘Com-Cov’. Anyone from Southampton or Hampshire and Isle of Wight wanting to take part can register online at www.comcovstudy.org.uk/participate-southampton. “The people of our city and region contributed massively to the trials that got these vaccines to the front line – we’re hoping they will come forward again to help us use the vaccines as effectively as possible. We’re really keen to hear from those between 50 and 70 years of age, especially those from a black or Asian background. No one taking part will receive a placebo, or dummy, dose – all receive two doses of the currently approved vaccines used by the NHS.” Comparing dose type and timing The study will test eight different combinations and interval doses for the Oxford/AstraZeneca and Pfizer/BioNTech vaccines. It will compare two doses of the same vaccine against one dose of each vaccine, with either the Oxford/AstraZeneca or Pfizer/BioNTech vaccine as the first dose. For each combination, the researchers will compare giving the two doses 28 days or 12 weeks apart. Undertaken by the National Immunisation Schedule Evaluation Consortium (NISEC) and the Oxford Vaccine Group, the study is backed by £7 million of government funding from the Vaccines Taskforce. It has received ethics approval, as well as approval from the Medicines and Healthcare products Regulatory Agency (MHRA) to commence. Vaccinations are expected to start towards the middle of February, with initial results to be made available over the summer period. The study will last for 13 months. If the study shows promising results, the MHRA would formally assess the safety and efficacy of any new vaccination regimen before it would be rolled out to patients. Those interested in volunteering at Southampton can find out more by visiting www.comcovstudy.org.uk/participate-southampton. The UK public can continue to support the national effort to speed up vaccine research and receive more information about volunteering for future vaccine studies by visitingwww.nhs.uk/researchcontact.

A pioneering ‘surgery school’ initiative developed by Southampton doctors has been shown to motivate patients to adopt healthier habits – helping them to take control and get into the best possible shape for their operations. Critical care researchers at UHS have shown 60% of the patients who attended their Fit-4-Surgery school and gave feedback planned to make lifestyle changes that would improve their health. The study results, published in the journal Anaesthesia, also found that 94% of these patients would recommend it to a friend having surgery. Exercise as medicine The Fit-4-Surgery school is one of a number of pioneering studies showing that ‘prehabilitation’ – getting into the best possible shape before and during major surgery and treatment – has significant benefits for patients’ wellbeing, quality of life and readiness for major surgery. Overall, 586/1017 (58%) of patients invited between May 2016 and December 2018 decided to attend, and 492 completed the anonymous feedback form at the end. They were all scheduled to have surgery, mostly colorectal and urological surgery. During the two hour session, given by nurses, dieticians and physiotherapists, the patients learned what to expect after surgery, and how – by improving their nutrition, boosting their fitness and giving up smoking and alcohol prior to their operation – they could enhance their recovery. Changing behaviour Of those who gave feedback after the session, most said they found it useful, and over half (60%) said they planned to make changes to their lifestyle to improve their health. Of the 232 patients who gave feedback after their operation, 46% said they had become more active, 41% had changed their diet, 61% had cut down on alcohol, and a few smokers had given it up. “Over the last 5 years the feedback we have had from patients has been phenomenal, they get so much out of it. Now being able to evidence that many who attend make healthy lifestyles changes that may improve their recovery is brilliant," said Imogen Fecher-Jones, lead nurse for the perioperative medicine service. “As a result of COVID, we are now delivering surgery school in a virtual classroom online, something we had not considered before but has been very positively received by patients and has seen attendance rates increase.”

A single dose of the Janssen coronavirus vaccine has been shown to protect 66% from infection and 100% protection from hospitalisation or death, in a 44,000 participant international trial. A single dose of the vaccine developed by Johnson & Johnson’s pharmaceutical subsidiary Janssen has been shown in a large international trial to be 66% effective in preventing coronavirus infection. Critically, no one in the trial who received the Janssen vaccine needed hospital treatment or died from coronavirus after the vaccine took effect. These results raise hopes of good results for an ongoing phase 3 Janssen trial, testing two doses of the vaccine, led in the UK by Southampton’s Professor Saul Faust. Single dose effective These results, based on nearly 44,000 participants and 468 cases of Covid-19, show the Janssen vaccine is effective as a single dose. Those effects, combined with its ability to be stored at standard fridge temperatures, indicate significant practical benefits for vaccination programmes around the world. The UK has ordered 30 million doses. The Janssen vaccine uses a common cold virus, genetically modified to make it harmless and to look more like the Sars-CoV2 coronavirus to the body’s immune system, training it to recognise and fight coronavirus. Taking part in vaccine trials 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. 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 can sign 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. A single dose of the Janssen coronavirus vaccine has been shown to protect 66% from infection and 100% protection from hospitalisation or death, in a 44,000 participant international trial.

Southampton’s Breathing Retraining for Asthma Trial of Home Exercises for Teenagers (BREATHE4T) study is assessing the use of an online tool to help teenagers better manage their asthma. Southampton teenagers with asthma are collaborating with researchers to build a mobile-ready website aimed at giving others like them access to breathing ‘retraining’ exercises they can do anywhere to improve symptoms and quality of life. Asthma care Asthma affects people of all ages, causing breathing difficulties including potentially life-threatening ‘asthma attacks’ (sudden worsening of symptoms). The UK has one of the highest rates of asthma in Europe, with 5.4 million people currently receiving treatment; 1.1 million of whom are children and teenagers. There is no cure for asthma, and while research has given us new treatment options and exercises for managing symptoms, making sure asthmatics are aware of these and able to take advantage of them remains a challenge – particularly amongst teenagers. To tackle this, the BREATHE4T study aims to create a mobile-friendly website carrying information on how breathing retraining exercises help and how they can be built into daily life. Developed by GPs, physiotherapists, psychologists and patients, the exercises have already shown strong benefits for adults when provided in DVD format – BREATHE4T aims to translate this into an online format tailored to teenage audiences. For teenagers, with teenagers Already 24 teenagers and parents are working with the study team to tailor the length and nature of the breathing retraining exercises for their peers, and a panel of teenagers and parents are helping design the website to be engaging and accessible for 12-17 year olds. This development stage is planned to run until 30 July 2020, with the team keen to hear from anyone who’d like to be part of the project. The aim is to then take the website into a trial involving 300-400 teenagers to assess the effects on their symptoms and quality of life. Get involved If you’d like to get involved in the study, please contact Stephanie Easton at S.E.Easton@soton.ac.uk.

Southampton researchers have won this year’s Health Services Journal Cancer Care Initiative of the Year award for their pioneering trial of ‘prehabilitation’ exercise and psychological support for cancer surgery patients. Professor Sandy Jack and her team have won the 2020 Health Services Journal’s award for Cancer Care Initiative of the Year for their WesFit trial. The award recognises outstanding dedication to making things better in the NHS. This genuinely transformational project has translated early studies in Southampton’s NIHR Biomedical Research Centre and NIHR Clinical Research Facility into a regional, then national trial of exercise and psychological ‘prehabilitation’ support for cancer surgery patients. The £2.3 million study compares the impact of pre-surgical exercise, psychological support or both combined. It was selected ahead of hundreds of other projects to win the award. “This is fantastic news for the team, the communities and the patients involved in the trial here in Wessex and elsewhere across the UK,” comments study lead, Professor Sandy Jack. Exercise as medicine WesFit is rapidly translating Professor Jack’s pioneering research into frontline clinical practice. Those studies showed that structured, high intensity exercise in the six weeks between chemotherapy and surgery returned patients’ physical fitness to pre-chemotherapy levels before they entered the operating theatre. Professor Jack’s team and the Wessex Cancer Alliance worked in partnership with cancer charities, leisure facilities and local councils across Wessex. “We know that in major surgery physical fitness has a big impact on how fast you recover, your chances of complications and your long term outcomes,” explains Professor Mike Grocott, head of the Southampton Critical Care Research group. “Not only have we shown this improvement in pre-surgery fitness, evidence of reduced complications and massively improved quality of life, we’ve also published data showing that this kind of exercise results in the tumour itself shrinking ahead of surgery.” “Together we’re establishing the evidence for a whole new approach to cancer surgery services – focussing on getting people into the best possible shape before their operation to improve recovery, outcomes and help them stay healthy for the rest of their lives,” adds Sally Rickard, Director of the Wessex Cancer Alliance. Adapting to COVID-19 restrictions Despite WesFit being paused in March due to Covid-19 restrictions, the team transformed it into a virtual service-as-a-trial known as SafeFit, providing remote exercise, dietary and emotional support for cancer patients with paused or disrupted treatment plans. This took the concept of the trial and offered a much broader range of support services to cancer patients across the UK, via an online platform and with the trained CanRehab instructors. SafeFit launched in April 2020 and has been an enormous success. Due to the current restrictions on ceremonies and events, the awards were presented on Twitter this year, with a series of presentations and films that were submitted to HSJ by each nominee. You can watch the team’s WesFit presentation here: https://vimeo.com/432500166/d880853d4b

Researchers, including Southampton’s Professor Keith Godfrey, found children in Singapore aged two to three years, whose screen time was limited to less than an hour a day were more active in later childhood. The new study, published in The Lancet Child and Adolescent Health, suggests that limiting toddlers’ screen time could help them develop healthy habits that mean they are more active in early childhood. Given the current rise in childhood obesity, this suggests limiting screen time when children are young could potentially help them to grow up living healthier, more active lives. Tracking children’s activity The researchers analysed data from 552 children in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study, which has tracked the long-term health of mothers and their children from birth since it started in June 2009. When the children were two to three years old, the parents attended a clinic where they were asked about their child’s daily screen viewing habits, including TV, mobile phones, tablets and computers. Then, when the children were five and a half years old, they wore an accelerometer on their wrist for seven consecutive days (including at night) to measure their activity. Toddlers in Singapore who spent less than an hour a day looking at screens were found to be more active at age at five and a half than toddlers who clocked up more than three hours a day. This may be due to screen time taking up time that children would otherwise spend doing something more active, like exercise or play. Fighting childhood obesity Childhood obesity is a growing problem worldwide. The World Health Organisation (WHO) estimated that in 2016 the number of overweight children under the age of five was over 41 million. These children likely to stay obese as adults, increasing their risk of developing diseases linked to obesity such as heart disease or type 2 diabetes. “The results from this study highlight the role reducing screen time in very young children could have in tackling the obesity crisis,” says Professor Keith Godfrey. “They suggest that restricting screen time for toddlers could help to establish healthy habits that stay with them throughout childhood, building the foundations for exercise in later life.”

Prof Tom Wilkinson’s research group has renewed a long-standing collaboration with AstraZeneca to understand the mechanisms driving the development of chronic obstructive pulmonary disease (COPD). Building on a four year collaboration between the two organisations, this renewed agreement will provide Prof Wilkinson’s group with funding for the next phase of the collaboration between AstraZeneca and the University of Southampton, a leading centre in understanding disease mechanisms of COPD and airway infection. Establishing a well characterised cohort of patients with COPD has allowed these scientists to investigate differences in gene expression which drive the immune response to viral infection in COPD. Some of this work has recently been published in the American Journal of Respiratory and Critical Care Medicine. COPD causes more than three million deaths a year worldwide. It is a major driver to hospital admissions and unscheduled visits to Primary Care. New treatments are desperately needed to improve outcomes for patients with the condition and this project will focus on that goal. Tom Wilkinson, Professor of Respiratory Medicine and Lead for COPD research at the University of Southampton, said: “I am really excited about continuing this important collaboration. "This programme of research aims to provide ground-breaking insights into disease mechanisms of COPD and will help us work towards the development of a new generation of therapies which are greatly needed for our patients.” Maria Belvisi, Senior Vice President and Head of Early Research and Development, Respiratory, Inflammation and Autoimmunity, BioPharmaceuticals R&D, AstraZeneca, commented: “Through this collaboration we will continue our multi-omics analysis of COPD patient samples, and I hope this will help us identify novel patient phenotypes and previously unknown pathways that lead to this chronic disease." By further increasing our understanding of the underlying biological drivers of COPD, we aim to develop a new generation of medicines that could modify the disease.”

Southampton researchers are testing a prototype of a personal respirator they have developed for frontline healthcare staff tackling the COVID-19 pandemic. If the tests are successful, they hope it will solve the limitations of existing protective equipment doctors and nurses are wearing on the wards. Rapid response Working with industry partners including McLaren and Kemp Sails to respond to the pandemic, the team had a prototype in testing in just a few days. The disposable surgical and FFP3 facemasks currently used in hospitals are constantly in high demand, and are not available in some settings. The early stage prototype developed in Southampton consists of a fabric hood which covers the wearer’s head, integrated with a plastic visor to protect their face. A small portable unit delivers clean air through a HEPA filter to the wearer from a battery powered fan pack mounted on a belt. The prototype uses off-the-shelf components, and has received positive feedback from doctors, nurses and patients in initial demonstrations at the hospital. Doctors and nurses will be testing the prototypes on the wards this week in the course of their day-to-day work, to provide comfort and usability feedback. Protecting staff If the tests are successful and the prototype obtains the necessary safety certifications, the concept will be published open-source so it would be available to other manufacturers and organisations around the world. The engineers on the team will also investigate developing simpler prototypes using only components available in developing countries. Paul Elkington, Professor of Respiratory Medicine at the University of Southampton said, "We must minimise the risk of infection for medical staff and stop them getting sick at the peak of the pandemic, so that they can care for others. The engineering team have rapidly developed something simple yet effective. "The HEPA filtered air removes 99.95% of particulate matter and the face mask protects from splashes, and so we think this will reduce the risk of infection." Hywel Morgan, Professor of Bioelectronics at the University of Southampton said, “This is an excellent example of industry, universities and hospitals combining their expertise and answering the call to develop solutions needed to save lives in the current crisis. “We are really grateful to our partners at McLaren, Kemp Sails and INDO on behalf of Baynhams for their commitment in working around the clock with us to getting this from a concept to a working prototype in a matter of days.” Whilst other personal respirators exist, they also face high demand. The successful deployment of this product on a large scale would help to increase the amount of protective equipment available to help keep healthcare workers safe, healthy and able to remain caring for patients. Making the design specification accessible online would mean this product could be manufactured in any country without facing export delays or restrictions. Further information on the product is available here.