The framework combines dimension reduction techniques and a new explainable clustering algorithm called CLASSIX, developed by mathematicians at The University of Manchester. This enables the quick identification of groups of viral genomes that might present a risk in the future from huge volumes of data.

, presented this week in the journal PNAS, could support traditional methods of tracking viral evolution, such as phylogenetic analysis, which currently require extensive manual curation.

Like many other RNA viruses, COVID-19 has a high mutation rate and short time between generations meaning it evolves extremely rapidly. This means identifying new strains that are likely to be problematic in the future requires considerable effort.

Currently, there are almost 16 million sequences available on the GISAID database (the Global Initiative on Sharing All Influenza Data), which provides access to genomic data of influenza viruses.

Mapping the evolution and history of all COVID-19 genomes from this data is currently done using extremely large amounts of computer and human time.

The described method allows automation of such tasks. The researchers processed 5.7 million high-coverage sequences in only one to two days on a standard modern laptop; this would not be possible for existing methods, putting identification of concerning pathogen strains in the hands of more researchers due to reduced resource needs.

, Professor of Mathematical Sciences at The University of Manchester, said: “The unprecedented amount of genetic data generated during the pandemic demands improvements to our methods to analyse it thoroughly. The data is continuing to grow rapidly but without showing a benefit to curating this data, there is a risk that it will be removed or deleted.

“We know that human expert time is limited, so our approach should not replace the work of humans all together but work alongside them to enable the job to be done much quicker and free our experts for other vital developments.”

The proposed method works by breaking down genetic sequences of the COVID-19 virus into smaller “words” (called 3-mers) represented as numbers by counting them. Then, it groups similar sequences together based on their word patterns using machine learning techniques.

, Professor of Applied Mathematics at The University of Manchester, said: “The clustering algorithm CLASSIX we developed is much less computationally demanding than traditional methods and is fully explainable, meaning that it provides textual and visual explanations of the computed clusters.”

Roberto Cahuantzi added: “Our analysis serves as a proof of concept, demonstrating the potential use of machine learning methods as an alert tool for the early discovery of emerging major variants without relying on the need to generate phylogenies.

“Whilst phylogenetics remains the ‘gold standard’ for understanding the viral ancestry, these machine learning methods can accommodate several orders of magnitude more sequences than the current phylogenetic methods and at a low computational cost.”

The paper, commissioned by the World Health Organization (WHO) and published in , builds on research already completed by both institutions during the pandemic which demonstrated that ethnic minority groups were disproportionately affected by COVID-19.

The paper brings together all of the available evidence, along with international experts in the field, to summarise why people from ethnic minority groups were more likely to be infected and die during the pandemic.

Researchers highlighted that ethnic minority groups were more likely to be exposed to those who were infectious with COVID-19 because a high proportion were employed in key worker roles, making it more likely that they would themselves become infected. They also showed that certain ethnic minority groups were more likely to die once infected due to barriers in receiving adequate healthcare, such as delayed diagnosis and treatment due to job insecurity and financial issues, and in some cases language barriers.

In addition, the research showed they were more likely to suffer from social and economic consequences – for example the inability to isolate once infected and in some cases the lack of adequate healthcare to meet their needs.

The authors state that ethnic minority groups were disadvantaged from the start due to longstanding health inequities caused by systemic racism and racial discrimination. Furthermore, the reasons for ethnic inequities in COVID-19 infection, severe disease and death are interconnected.

The paper aims to provide a blueprint for policymakers and researchers to address these inequities so that they can be better prepared for future pandemics.

It states that a ‘one size fits all’ approach to intervention does not work and that cultural, social and language barriers must be overcome along with other socio-economic issues.

“This framework is the first of its kind to specifically address inequities during a pandemic,” said Dr Daniel Pan from the University of Leicester, the paper’s co-lead author who is a specialist registrar in Infectious Diseases and General Internal Medicine and a National Institute for Health and Care Research (NIHR) Doctoral Research Fellow. “The recommendations aim to ensure ethnic inequalities in treatment do not occur in future.

“The COVID-19 pandemic won’t be the last and steps need to be taken now to reduce the inevitable consequences of the next pandemic on ethnic minority groups. We know that innovative approaches are required but if we plan for these, they can be overcome.”

“The COVID-19 pandemic has highlighted and amplified health inequalities for ethnic minority groups,” said Professor of Clinical Infectious Diseases Manish Pareek from the University of Leicester, the paper’s senior author.

“It is important that we learn lessons from the pandemic and this work, in collaboration with international experts and the WHO, provides guidance on how to reduce the disproportionate impact on ethnic minority groups for future pandemics.”

As the next stage of the Covid Inquiry opens, charity Versus Arthritis and the University of Manchester reveal evidence of the brutal toll shielding had on people’s lives, including some who were forced to stop living with their children and others who lost their jobs.

Covid Shielding Voices, funded by Versus Arthritis, reveals how shielders felt that society treated them like “second-class citizens” after lockdowns lifted and shielding support was removed, including being discriminated against in the workplace.

Deborah Alsina MBE, Chief Executive of Versus Arthritis, says “people should not be punished for having a health condition. There is a profound opportunity for the Covid Inquiry to learn from the experiences of those who shielded and to understand what went wrong.”

The charity is asking the Inquiry to acknowledge the serious failings by Government on shielding and that more can be done to protect vulnerable groups now and in the future.

4.1 million people across the UK were identified as clinically extremely vulnerable (CEV) to Covid-19 and were asked to shield during the pandemic. People with conditions like rheumatoid arthritis were among this group because their condition and the medicines they are prescribed can weaken the immune system.

Participants in the study, led by patients and researchers at The University of Manchester, initially felt protected by the shielding programme but say they were “thrown to the wolves” when it suddenly ended on 15^th September 2021, citing the lack of support to protect them as the rest of society opened up.

Patients and researchers worked together to analyse the experiences of people with autoimmune arthritis and rheumatic conditions who shielded, and to show what lessons can be learned from their stories for future pandemic planning.

Participants’ experiences are varied, covering the impact on home and work life; difficulties in accessing healthcare; the effect on self-identity and place within society after isolating for so long; and the feeling of abandonment when formal shielding ended.

The study found many examples of people being discriminated against at work due to their need to follow shielding guidance. Some say they have been met with “tutting” and “eyes rolling” for following occupational health advice, such as avoiding work areas, while others were made redundant from their jobs. Those who were supported to work from home have felt “excluded” and disadvantaged, “missing out on those important conversations”. 

Shielding impacted family relationships and often disrupted family members’ ability to attend school and work, leading to extraordinary personal sacrifices. One mother explains how she contemplated whether sending her child to school was more important than her own survival: “Is putting [my child] first sending them to school and letting them live a normal life […]? Or is putting them first protecting their mum so that there’s less risk that they one day don’t have a mum? Where do you draw the line, what’s more important?” Another woman who faced the same dilemma ended up moving out of the family home.

Versus Arthritis supported thousands of people with conditions like rheumatoid arthritis who shielded throughout the pandemic, including Professor Martin Eve, 37, who lives with his wife in Kent. Martin has rheumatoid arthritis (RA), which caused him to develop secondary immunodeficiency – where the immune system is weakened by another treatment or illness – and ultimately kidney failure. He is still shielding today. He said:

“At times, shielding has been extremely depressing. At other times, reassuring. I was very grateful it was there, as it meant I was safe. I could do most of my job from home too at that point. It was when the support evaporated, and it became our own personal responsibility to avoid catching Covid, that things became much harder.

“I had to change my job to continue to work from home full time. To this day, the official guidance for vulnerable people is basically: ‘Avoid people who have covid infections.’ But the Government withdrew everything that would help us do that. The subtext is that you will have to just avoid society if you can’t avoid people with Covid.”

Lynn Laidlaw, a patient and member of the research team who also had to shield, said:

“We felt it was important to bring the existing, mainly data driven, research into shielding to life. Our research sought to understand people’s experiences and the impact of shielding by talking to them about their experiences. It highlighted the importance of personal context, including employment and family situations, pushing back against the narrative that everyone who shielded is similar and were ‘going to die anyway’.

“It highlighted the work involved in managing shielding, alongside the work of living with long term, chronic conditions. The participants in this research wanted, and deserved, to be treated as individuals by society, and to receive medical advice and care that understood their personal situation.”

Deborah Alsina MBE, Chief Executive of Versus Arthritis, said:

“This timely report is a stark reminder of the impact Covid-19 had not only on people with autoimmune arthritis and rheumatic conditions, but everyone who shielded. The findings show that people in this group are not being met with the empathy they deserve.

“We want the Covid Inquiry to acknowledge the serious failings by Government on the shielding programme and the manner in which it ended. Learning from these mistakes and from the experiences laid out in our report will enable all of us to do more to protect vulnerable groups now and in the future, starting with the absolute basics – greater understanding and kindness towards those who shielded.”

Dr Charlotte Sharp, lead researcher of the study at the University of Manchester and consultant rheumatologist, said:

“Shielding was a necessary and hugely important intervention to protect people who were more vulnerable to COVID-19 than the healthy population. Participants told us their frustration about how shielding was initiated, including a lack of clarity on who should be included, and wide variation in communications about the need to shield. People had difficulty accessing food and medicines making them have to choose between staying safe and getting these basic supplies.

“The most harrowing time for many shielders who participated in our study was ‘freedom day’. Whilst the rest of society regained their freedom and went ‘back to normal’, shielders were no longer protected by measures such as social distancing and mask-wearing. To stay safe their freedom was more curtailed than previously, leading some to describe this as ‘incarceration day’. We want the Covid Inquiry to learn lessons from the challenges faced by shielders to inform policy for future pandemics.”

The study - led by Professor Filippo Varese, Director of the Complex Trauma and Resilience Research Unit (C-TRU) at GMMH and the University of Manchester (UoM), Dr Paul French, Reader at 91ֱ�� Metropolitan University (MMU) and Clinical Academic at Pennine Care NHS Foundation Trust, and Dr Kate Allsopp, Research Fellow at GMMH and UoM - also emphasises the need to preserve the staff wellbeing hubs going forward as accessible, confidential sources of help for health and social care staff.

As the COVID-19 pandemic became associated with high levels of mental health difficulties such as anxiety, depression, post-traumatic stress disorder, and burnout among health and social care staff, the NHS funded 40 wellbeing hubs in England to support staff. The wellbeing hubs were modelled after which was established to support people affected by the 91ֱ�� Arena attack in 2017.

The staff wellbeing hubs (also known as Resilience Hubs) provided a variety of support to health and social care staff, who could self-refer to the services. Support offered included proactive outreach, rapid clinical assessment, access to evidenced-based psychological care, where required, and support for staff teams.

Between 2020 and 2022, the study evaluated four of these staff wellbeing hubs in the North of England.

In-depth interviews were conducted at three hubs with a diverse range of participants, including health and social care staff who used and did not use the staff wellbeing hubs for support, staff who worked at the hubs, and stakeholders involved in supporting staff within their organisations, such as occupational health and HR leads.

A total of sixty-three interviews were carried out in order to understand more about how the staff wellbeing hubs were set up, and people's experiences of getting mental health support during the pandemic.

“The Resilience Hubs were found to be important sources of support, which not only helped staff during the exceptional circumstances experienced during the pandemic but can also continue to do so going forward in the next stages of the NHS's recovery journey and beyond” says Dr Kate Allsopp, lead author of the paper. “Too often, workplace stress is seen as ‘just part of the job’ and often participants told us they waited until they were at breaking point before getting support, so the hubs’ model, which reaches out to offer support specifically to this group of staff, is vital.”

"The study's key findings demonstrate that the staff wellbeing hubs were perceived as a valuable source of support for staff, who reported very positive experiences,” said Professor Filippo Varese, the study's chief investigator. “Our research also emphasised the need for managers and employing organisations to genuinely and actively promote mental health support to staff, which can make an important difference to whether staff feel safe enough to seek support, he said”.

This study's findings emphasised the importance of health and social care employers prioritising and promoting mental health support for their employees. It also highlighted the need to create psychologically safe work settings and to resolve workplace stressors that can negatively impact on staff wellbeing, in order to prevent the development of mental health difficulties.

“Our research found the support provided through the resilience hubs was of real value. The stresses placed on health and social care staff during the pandemic were extreme; providing this additional support was an important step. Many staff continue to experience difficulties and these hubs continue to play a vital role for many. The real value of these hubs should be seen longer term with the ability to ramp up support in response to a wide range of complex large-scale incidents that affect our society,” said Dr Paul French.

The study recommends further outreach, and promotion in the future to raise awareness of the services provided by staff wellbeing hubs.

It also underlines the importance of diversity and cultural competence training in order to better meet the needs of underrepresented populations.

The findings are consistent with global studies and have significant policy implications for the entire health and care system. The findings are relevant not only in the context of the conditions brought about by the pandemic, but as part of ‘business as usual’ and in preparation of future crises that might, once again, severely tax the health and social care workforce.

The findings, funded by Health Data Research UK  and the National Institute for Health and Care Research (NIHR), is published in eClinical medicine, act as a warning against the overuse of antibiotics in people.

The team, which also included researchers from the Universities of Oxford and Leeds, were the first to explore how the severity of COVID-19 disease is affected by prior antibiotic use.

The research team found:

• Patients with more frequent antibiotic exposure in the past three years were at higher odds of experiencing severe COVID-19 outcomes, including hospital admission and 30-day mortality.
• Using a range of antibiotics was more likely to be associated with COVID-19 hospital admission.
• The odds for hospitalised patients dying from COVID-19 related complications in most frequent antibiotics exposure group were 1.34 higher than patients without prior antibiotic exposure.
• Larger number of prior antibiotic type was also associated with more severe COVID-19 related hospital admission
• The odds of hospitalisation for patients with the highest history of prior antibiotic use and most antibiotic types were 1.8 times greater than patients without antibiotic exposure.

The NHS OpenSAFELY platform, a secure open-source software platform for analysis of electronic health records allowed the researchers to integrate primary and secondary care, COVID-19 test, and death registration data from February 2020 to December 2021.

The sample included 0.67 million patients from an eligible 2.47 million patients with recent COVID-19 infection.

Of the 0.67 million, 98,420 patients were admitted to hospitals, 22,660 died and 55 unique antibiotics were prescribed.

Cases were identified by the researchers according to different severity of COVID-19 outcomes and they created five groups, based on the number of previous three-year antibiotic prescriptions to indicate the frequency of prior antibiotic exposure.

Each group was further split based on the number of different antibiotic types a patient was prescribed.

Co-principal investigator Professor Tjeerd van Staa from The University of Manchester said: “Our study has provided evidence that patients with high prior antibiotic use were more likely to experience severe COVID-19 outcomes, including hospital admission and even death.

“In addition, we also found an association between the number of different prior antibiotic types and COVID-19 related hospital admission.

“One potential explanation may be that frequent antibiotic use increases the likelihood of patients being infected with viruses or bacteria, leading to increased susceptibility to adverse consequences of infection.

“The literature also shows that antibiotic treatment might also alter gut microbiota, which can impact metabolic and immune function.

“While in most situations, gut microbiota will recover after stopping an antibiotic course, frequent antibiotic use may affect the resilience of gut microbiomes more seriously.”

Co-principal investigator Dr Victoria Palin from The University of Manchester said: “There is little evidence to suggest that repeated intermittent antibiotic exposure is effective in reducing infection-related complications. Indeed, there is mounting evidence that it can be unsafe.

“That is why there needs to be more awareness of the impact of long-term antibiotic exposure and its adverse outcomes. We would discourage regular and indiscriminate prescribing of these drugs for self-limiting infections.

“Common infection guidelines in England, as developed by the National Institute for Health and Care Excellence, focus on the treatment of the first infection episode .

“They do not provide guidance around repeated antibiotic use and a patient’s risk of developing resistance.

“Antibiotic prescribing guidelines should also clearly outline the possible adverse consequences to a patient of using an antibiotic for self-limiting bacterial infections. Personalised patient leaflets should be provided highlighting these risks and the risks of the patient’s bacteria developing resistance to antibiotics”

To fill this gap, - written by Lecturer in Architectural Studies Camilla Lewis, Professor of Sociology and Social Gerontology Chris Phillipson, Research Fellow Sophie Yarker and Research Associate Luciana Lang - provides new insights into the challenges facing older people during the COVID-19 pandemic. 

The authors drew upon the experiences of a diverse group of 102 people aged 50+ from Greater 91ֱ��, as well as 21 community organisations collected over a 12 month period during the pandemic.

They found that older people were disproportionately affected by the emergence and spread of COVID-19, whether in hospital, the community or in care homes. More than 80% of deaths related to the virus between 2020 and 2021 occurred among people aged 60 years or older. 

COVID-19 created new pressures for people of all ages throughout the world, but it raised particular concerns for older age groups. The book highlights the challenges older people faced when forced to ‘stay apart’ from family and friends and identifies changes affecting people over the course of three successive lockdowns.

For older people themselves, there were a variety of reactions to the pandemic. Few were left untouched by its profound effects on the routines and relationships which make-up daily life. The book conveys the challenges and responses across the different organisations and groups of older people interviewed, examining  issues such as the impact of social distancing, the effects of shielding, and the experience of social isolation.

COVID-19 amplified existing insecurities, as people struggled to cope with long-term illnesses in the context of pressures from reduced health and social care support. Reflecting this, the research suggests the pandemic has introduced new vulnerabilities, exacerbating further the precarious lives of  different groups of older people.

The authors raise concerns about the negative attitudes towards older people which arose during the pandemic, and which have continued to influence debates around a range of social and financial issues.

They recommend developing a ‘community-centred approach’ in responding to future  pandemics, with a focus on the importance of enhanced funding for community organisations, supporting leaders within neigbourhoods, and providing advocates for those who have difficulty securing the services they need.

“This book provides a detailed account of how the daily lives of older people were affected by COVID-19. It highlights the variety of responses from groups and neighbourhoods across Greater 91ֱ�� and documents the important work of voluntary and community organisations and the crucial role which they played in providing support to vulnerable groups. The book makes a case for working directly with communities, both in preventing another pandemic and addressing the injustices exposed by COVID-19,” said Camilla Lewis.

COVID-19, Inequality and Older People was published by Policy Press, and is available through Open Access at .

The virus has been blamed for a range of health problems including hearing loss and other auditory disorders.

However, the global prevalence of Covid-19, and the importance of hearing for human interaction, means it is important to understand whether and how the virus might affect hearing, say the research team.

Lead authors Dr Anisa Visram and Dr Iain Jackson from the University of Manchester and a team of scientists compared two groups of patients who had been hospitalised, one group with Covid-19 and the other without Covid-19.

After completing the most comprehensive assessment of hearing to date, using a range of lab-based behavioural and physiological measures as well as self-report they were able to show that there was almost no difference in hearing between the two groups.

The findings are published in the International Journal of Audiology.

The study was funded by gifts to The University of Manchester’s Covid-19 Research Appeal, and part funded by RNID, The Dowager Countess Eleanor Peel Trust, and NIHR 91ֱ�� Biomedical Research Centre (BRC).

Dr Anisa Visram said: “We know that viruses such as measles, mumps and meningitis can damage the auditory system. It is also well known that Covid-19 can affect our sense of smell and taste so it was reasonable to assume it might also affect our sense of hearing. Our study was well designed and executed, and we believe it is the most thorough assessment of hearing conducted in people with Covid-19.”

Kevin Munro, Professor of Audiology at The University of Manchester and 91ֱ�� BRC Hearing Health lead said: “There was an urgent need for this carefully conducted clinical and diagnostic study to investigate the long-term effects of Covid-19 on the auditory system. Many previous studies were published rapidly during the pandemic but lacked good scientific rigour.”

The World Health Organisation refer to the avalanche of information produced during the Covid-19 pandemic as an infodemic. The vast quantity of sometimes misleading data has the potential to undermine trust in health institutions and health research.

Dr Ralph Holme, Director of Research and Insight at RNID, the charity supporting people who are deaf, have hearing loss or tinnitus, said: “We were pleased to support this study because we know hearing loss can have a significant impact on people’s lives. The study provides important public health information andit is reassuring to know that for the majority of people, hearing loss is not a major long-term consequence of Covid-19.”

A small number of people with Covid-19 reported greater effort required to listen but no specific auditory abnormalities were noted. This is an intriguing finding and may be related to wider post-viral effects such as fatigue and cognitive impairment.

Professor Richard Ramsden, Trustee at the Dowager Countess Eleanor Peel Trust said: “There have been many reports of hearing loss following Covid-19. It hasn’t been clear if these are incidental findings or if Covid-19 is damaging the hearing system. While the study cannot rule out infrequent hearing loss as a result of Covid-19, we now know that for most people, there is nothing to be concerned about.”

The research team used a state-of-the art bespoke hearing research van to travel to the homes of patients after they were discharged from hospital, making the study accessible to people who might not otherwise have been able to participate.

This unique research facility has already been used by the team in a previous study to improve the accuracy of hearing aid fittings in babies.  Now that the Covid-19 study has been completed, the research van is being used to assess the feasibility of travelling to different locations to collect data from adults with tinnitus. 

Anyone interested in participating in research on hearing loss and auditory disorders can register with the volunteer database at the university’s 91ֱ�� Centre for Audiology and Deafness. 

The study of patients in 38 institutions across the UK was led by The Universities of Manchester and Leicester,  presented at the European Congress of Clinical Microbiology & Infectious Diseases (Copenhagen, 15-18 April)  and published in Lancet Respiratory medicine.

The team discovered that 62% of participants  who had been admitted to hospital for COVID-19 had sleep disruption, which was likely to persist for at least 12 months, and highlight for the first time the association between two post-COVID condition symptoms: breathlessness and sleep disruption.

On average, participants who had been hospitalised with COVID-19 slept for over an hour longer, but their sleep patterns were less regular (19% decrease on the sleep regularity scale), than matched participants who were hospitalised due to any cause.

The study researchers also found that participants with sleep disturbance were more likely to have anxiety and muscle weakness, common post-COVID-19 condition symptoms. 

Statistical analysis identified that sleep disruption was likely to drive breathlessness directly, but that reduced muscle function and increased anxiety, both recognised causes of breathlessness, could partially mediate the association between sleep disturbance and breathlessness.

The study authors speculate that targeting sleep disruption by reducing anxiety and improving muscle strength in these patients could alleviate breathlessness, but further investigation is needed.

The study used extensive data from the hospitals taking part in the study between March 2020 and October 2021.

PHOSP-COVID is a consortium from across the UK, researching long-term health outcomes for patients hospitalised with COVID-19.

The study was funded by the UK Research and Innovation, Asthma + Lung UK and others.

Sleep quality was assessed using subjective measures that were self-reported by 638 patients to researchers.

It was also measured objectively in another 729 patients, who wore devices similar to smart watches that measured night-time activity levels.

Both measures consistently revealed a higher prevalence of sleep disturbance in people who had been hospitalised with COVID-19 compared with matched controls from the UK Biobank who had been hospitalised for any cause.T

The impact on sleep from  hospitalisation due to COVID-19  was irrespective of critical care admission.

One of the authors Dr John Blaikley, a clinical scientist from The University of Manchester and respiratory doctor said : “This study has discovered that sleep disturbance could be an important driver of post-COVID-19 breathlessness – or dyspnoea - because of its associations with reduced muscle function and anxiety.

“If this is the case, then interventions targeting poor sleep quality might be used to manage symptoms and convalescence following COVID-19 hospitalisation, potentially improving patient outcomes.”

First author and mathematician Mr Callum Jackson from The University of Manchester said: “Understanding the causes of breathlessness is complex since it can arise from conditions that affect the respiratory, neurological, cardiovascular, and mental health systems.

“These same systems are also affected by sleep disturbance, another symptom that has been frequently reported after COVID-19.

“Our findings suggest that sleep disturbance is a common problem after hospitalisation for COVID-19 and is associated with breathlessness.

“We also show this is likely to persist for at least 12 months as subjective sleep quality did not change between 5 and 12 month follow-up visits.”

Professor Chris Brightling from the University of Leicester said: “The strengths of our study include its size, multicentre nature, and the use of different complementary assessment measures to evaluate sleep disturbance. Consistent clinical associations were also observed across each evaluation method.”

“Future research should now assess whether interventions targeting sleep disturbance can improve not only sleep quality but also breathlessness through reducing anxiety and improving muscle strength.”

The team was from The University of Manchester, 91ֱ�� University NHS Foundation Trust (MFT), Northern Care Alliance Foundation Trust (NCA), and the National Institute for Health and Care Research (NIHR) 91ֱ�� Biomedical Research Centre (BRC).

Normally functioning monocytes, made in the bone marrow, would travel through the blood to the lungs where they surround and kill the virus and boosts the immune response.

However,  scientists and clinicians discovered that  in long-COVID, abnormal migration of these cells corresponds to the most commonly reported symptom, shortness of breath. A different migration profile alongside changes to other functions correspond to fatigue.

The unique monocyte signatures defining subgroups of long COVID patients reveal new pathways that could targeted for novel therapeutic opportunities in long COVID patients.

The study is published today (16/03/23) in the European Respiratory Journal .

The patients were recruited to the study between July 2020 and January 2021.

They included 71 hospitalised patients with acute COVID-19 and 142 follow up patients attending outpatient clinics months after hospital discharge from COVID-19, across 91ֱ�� University NHS Foundation Trust and the Northern Care Alliance Foundation Trust.

Using blood samples, they examined key monocyte migratory signatures in acute disease that persisted into convalescence up to nine months following hospital discharge.

The hospitalised patients were arranged into mild, moderate and severe disease based on their oxygen requirements.

Patients on acute non-invasive ventilation, invasive ventilation and admission to intensive care automatically led to classifying patients as having severe disease.

Healthy blood samples were obtained from frontline workers at the University of Manchester and 91ֱ�� University NHS Foundation Trust (MFT) and examined alongside patient samples.

At outpatient review, patients undertook rigorous questionnaires which assessed whether they had increased levels of breathlessness and/or fatigue, and if this was new since SARS-Cov-2 infection.

Unique monocyte profiles distinguished long COVID patients with shortness of breath and unresolved lung injury from those with ongoing fatigue, and from asymptomatic patients.

The study was funded by The Wellcome Trust, the Royal Society, The Medical Research Council, The Kennedy Trust for Rheumatology Research, The Lister Institute, BBSRC and UKRI

Dr Elizabeth Mann, Wellcome Trust/Royal Society Sir Henry Dale Fellow at The University of Manchester’s said: “There is now a wealth of evidence indicating that chronic morbidity persists in many COVID-19 patients during convalescence manifesting as long COVID which remains a global public health problem despite vaccination programmes and milder strains of SARS-CoV-2.

“These debilitating symptoms including extreme fatigue, shortness of breath, myalgia, brain fog, depression, fibrotic lung disease and pulmonary vascular disease and we now know this can last for many months or even years following infection.

“But treatment options for long COVID are currently limited, since the development of targeted therapeutic strategies requires an in depth understanding of the underlying immunological pathophysiology.

“Our work finding a link between monocyte function and specific long COVID symptoms may provide an important first step on the road to possible treatments.”

Professor of Inflammatory Disease, Tracy Hussell is  Programme Lead in the Next Generation Phenotyping and Diagnostics Theme at NIHR 91ֱ�� BRC and Director of the Lydia Becker Institute at The University of manchester 

She added: “This study, led by Dr Mann's team, is a prime example of the ‘one 91ֱ��’ approach that provides seamless integration between clinicians and scientists under the umbrella of our NIHR Biomedical Research Centre and the generosity of our patient population.”

The paper Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID is  published in the European Respiratory Journal  .

“Our study examines COVID-19 outcomes from ethnic minority groups globally,” said Dr Daniel Pan, joint lead author and NIHR Doctoral Research Fellow from the University of Leicester. “Although now there are reductions in mortality amongst ethnic minority groups in the UK, our work is of relevance to policy makers internationally, where ethnic minority groups continue to suffer disproportionatey worse outcomes from COVID-19.”

“This latest study, now of over 200 million individuals from around the world, confirms and builds on our earlier work highlighting the disproportionate risk of COVID-19 in ethnic minority groups,” said Professor Manish Pareek, Chair in Infectious Diseases at the University of Leicester. “This work will be of relevance to UK’s independent public inequiry into the pandemic, which has committed to examining the impact of inequalities at the forefront of its investigations. Going forward it is critical that policy-makers address health inequalities to improve health outcomes for ethnic minority groups. 

“The COVID-19 pandemic shone a spotlight on the health inequalities experienced by ethnic minority groups,” said Professor Vittal Katikireddi, Professor of Public Health and Health Inequalities at the University of Glasgow. “Monitoring these inequalities in the future will be important to ensure policy responses are helping create a fairer society.”

This work was supported by the Economic and Social Research Council [grant number ES/W000849/1].

The briefing was also written by Professor James Nazroo and Dr Patricia Irizar of The University of Manchester, as well as Dr Richard Shaw of the University of Glasgow. It draws on a longer article published in , and is part of a by the Runnymede Trust and the Centre on the Dynamics of Ethnicity (CoDE) on the impact of COVID-19 on people from ethnic minority groups.

About the Economic and Social Research Council 

The Economic and Social Research Council () is part of UK Research and Innovation (), a non-departmental public body funded by a grant-in-aid from the UK government. We fund world-leading research, data and post-graduate training in the economic, behavioural, social and data sciences to understand people and the world around us. Our work helps raise productivity, address climate change, improve public services and generate a prosperous, inclusive, healthy and secure society.  

Designed by a team at The Universities of 91ֱ�� and , and the , the revolutionary design will protect wearers from viruses such as COVID-19.

The need for safe and effective covering remains important to protect wearers and bystanders for some groups. This can include elderly people or those who are are immunosuppressed (have a weakened immune system).

[1] by Dr Gaby Saunders, Senior Research Fellow at The University of Manchester, showed how opaque masks were associated with anxiety and stress in both the talker and the listener, spurring the project.

Dr Saunders, who manages 91ֱ�� BRC’s Hearing Device Centre, said: “Facial expressions are used extensively in communication, even among hearing people, and our research showed how face mask wearers feel less connected, less willing to engage in conversation.

“That is linked to increased anxiety and stress, as well as fatigue, frustration and embarrassment in both the listener and speaker.”

A 12-month ‘rapid-response’ grant from allowed research audiologists at The University of Manchester, Dr Michael Stone, Marston Senior Research Fellow, and Professor Kevin Munro, Honorary Consultant Clinical Scientist at , to assemble a team of experts.

The funding for a study to improve the design of masks was awarded by the .

Dr Stone, who is also 91ֱ�� BRC Developing Engineering Solutions Programme Lead, consulted with members of the Deaf community and people with experience of hearing loss.

Feedback from the community, and other users, allowed the team to refine the design, which was validated in a recent paper in [2].

Professor Trevor Cox, from the acoustics research centre at the University of Salford, and the team, also based there, developed a re-usable cotton-based mask design, allowing it to be manufactured widely.

The design incorporates an optically transparent panel, supported on a thin ‘scaffold’, which produces less muffling of sound than a conventional opaque mask with the acoustic signal (sound) from the mouth.

Prof Cox said: “By reducing the weight of the transparent plastic, we could stop the high frequency parts of speech being lost in the mask. The scaffold to support the thin plastic sheet is carefully designed not to hinder the sound.”

Dr Stone said: “This is a brilliant linking up of two diverse academic pursuits, psychology and physics, to produce real-world benefit for a wide range of people.

“The optical panel has also been shown to be effective  in face visors, and we are now looking for commercial partners so as to extend the reach of the designs and prototypes as well as incorporating a novel lightweight filtration material developed at The University of Manchester.”

Templates for the mask designs, available in three sizes, and a link to a “how-to-make” video hosted on YouTube are available at [3]

[1] Saunders G.H., Jackson I.R., Visram A.S. (2021) Impacts of face coverings on communication: an indirect impact of COVID-19, International Journal of Audiology, 60:7, 495-506, https://www.doi.org/

[2] Cox T.J.,  Dodgson G., Harris L., Perugia E., Stone M.A., Walsh M. (2022) Improving the measurement and acoustic performance of transparent facemasks and shields.  J. Acoust. Soc. Amer. 151, https://www.doi.org/10.1121/10.0010384

[3] Maker Space URL for templates & video. https://hub.salford.ac.uk/sirc-acoustics/facemask-with-improved-communication/

The Vaccine Response On Off Methotrexate (VROOM) trial, which will have implications for people on immune-supressing medicines, who are among the millions of clinically vulnerable patients advised to ‘shield’ during the pandemic – is funded by the National Institute for Health and Care Research and the Medical Research Council. It was carried out in collaboration with colleagues from the University of Manchester, Imperial College London, the University of Oxford and Queen Mary University London. The study was run by the Oxford Clinical Trials Research Unit (OCTRU).

The results of the study are published in Lancet Respiratory Medicine.

The study was planned to recruit 560 patients but recruitment was stopped early by the independent study oversight committees when interim results from the first 254 participants showed a clear result.

Methotrexate is the most commonly used immune-suppressing drug, with around 1.3 million people in the UK prescribed this medicine for inflammatory conditions such as rheumatoid arthritis, and skin conditions such as psoriasis. Many of them were among the 2.2 million clinically extremely vulnerable people advised to shield during the first phase of the COVID-19 pandemic, depending on specialist advice and on their risk factors.

While methotrexate is effective at controlling these conditions and has emerged as first line therapy for many illnesses, it reduces the body’s ability to fight infections and the ability to generate robust response to flu and pneumonia vaccines, including those against COVID-19.

The VROOM trial looked at the impact of interrupting methotrexate treatment for two-weeks after a COVID-19 booster vaccination on vaccine responses in adults with autoimmune inflammatory conditions.

Patients older than 18 years in age were recruited from dermatology and rheumatology outpatients in 26 NHS hospitals across England and Wales. The trial evaluated temporarily stopping versus continuing methotrexate treatment immediately after the third-prime dose or booster of the COVID-19 vaccine.

During the trial 127 participants were asked to suspend methotrexate use for two weeks and 127 to continue using it as usual. The decision on who stopped or continued with methotrexate treatment was made by a computer program – similar to tossing a coin or rolling a dice.

The team compared the spike-antibody levels between the two groups four weeks and twelve weeks after they had received a COVID-19 vaccine dose. The spike-antibody blocks the virus from infecting cells inside the body.

The team compared the spike-antibody levels between the two groups four weeks and twelve weeks after they had received a COVID-19 vaccine dose. The spike-antibody blocks the virus from infecting cells inside the body.

After 4 weeks and 12 weeks, the spike-antibody level was more than two-fold higher in the group where methotrexate was suspended for two-weeks following vaccination, compared to the group who continued use. There was a worsening of disease control at week 4 in the suspend group, but that had normalised by week 12. There was no impact on quality of life or general health.

Given the initial findings of the study, the independent study steering committee advised to stop further recruitments into the VROOM trial. Participants who took part in the VROOM study are being invited to participate in an additional visit six months after their vaccination date.

The spike-antibody level reflects the strength of the antibody response. The research team are currently examining the quality of the antibody response by measuring its ability to kill live SARS-CoV-2 viruses and other variants of concern such as Omicron. 

Chief Investigator, Professor Abhishek at the University of Nottingham and Honorary Consultant Rheumatologist at Nottingham University Hospitals NHS Trust, said: “We are extremely pleased with the initial results of the VROOM trial. There was a doubling of the antibody response in patients who held off on taking methotrexate for two weeks. The improvement in antibody response was maintained over a 3-month period. There was a short-term increase in risk of flare-up of inflammatory conditions. However, most could be self-managed.

“We also saw no adverse impact on the quality of patient’s life following suspension of their medication. However, the study did not evaluate whether this strategy would result in fewer cases of COVID-19 or fewer hospitalisations due to COVID-19 as it was not large enough to detect these differences.

“Implementing these results could vastly improve the protection provided by boosters against COVID-19 for millions of people living with these conditions. Covid-19 has left them vulnerable to serious illness, whilst still having to live with the painful and troubling effects of their conditions. We hope this evidence is the next step in helping them with their lives going forward.”

Professor Andy Ustianowski, NIHR Clinical Lead for the COVID-19 Vaccine Research Programme and Joint National Infection Specialty Lead and an Honorary Clinical Chair at The University of Manchester, said:

“Despite the majority of the UK population now being vaccinated, it remains as important as ever to continue ongoing research to ensure we can use vaccines effectively in different groups of patients.

“These landmark results provide high quality evidence to help best protect millions of people with compromised immune systems, keeping them safer from the virus and their existing chronic conditions.

“Thank you to all the participants who took part, we rely on their continued commitment to help us learn more and ultimately beat the virus.”

Joint lead applicant Professor Rosemary Boyton, Professor of Immunology and Respiratory Medicine, Department of Infectious Disease, Imperial College London and Lung Division, Royal Brompton Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK said: “This study is the first to report the effectiveness of a two-week interruption of an immunosuppressant drug called methotrexate immediately after COVID-19 booster vaccination to enhance antibody binding immunity against SAR-CoV-2. Our results showed a doubling of antibody levels, an increase that was sustained at 12 weeks. This has important implications for future vaccination strategy in this immunosuppressed patient group.”

OCTRU Academic Lead, Associate Professor Jonathan Cook based at the University of Oxford said: “It’s pleasing to see the difference that a simple, cheap and modest adjustment to treatment can make. Clinical trials like VROOM are needed to help us understand how best to deliver vaccinations like a COVID-19 booster in different patient groups.”

Professor John Iredale, Executive Chair of the Medical Research Council, which part-funded the trial, said: “This important finding means many people who need to take immune-suppressing medicines now have a safe and effective way to improve their immune response to life-saving COVID-19 vaccines. This study shows yet again how the UK research community’s world-leading ability to rapidly set up well-designed clinical trials can deliver the evidence needed to optimise medical interventions and save lives in the pandemic.”

More information on the study is available on , and on the . 

The findings by scientists from The University of Manchester and published as a research letter in the are good news for patients with the common condition.

Chronic obstructive pulmonary disease, or COPD, makes it difficult for air to get in and out of the lungs causing breathlessness, coughing and frequent chest infections.

According to the British lung Foundation, an estimated 1.2 million people are living with diagnosed COPD in the UK, making it the second most common lung disease in the UK, after asthma.

Around 2% of the whole population and 4.5% of all people aged over 40 – live with diagnosed COPD.

COPD patients have a higher risk of developing severe illness and mortality following COVID-19 infection.

As COPD patients are known to have a reduced immune response, doctors feared COVID-19 vaccination might be less effective on them.

The scientists compared the  SARS-COV-2 vaccine- specific immune responses in COPD patients with healthy people, using blood, nasal and airway samples.

Vaccinated individuals, who had never been infected with COVID-19, donated samples more than two weeks after completing two doses of either the Oxford-AstraZeneca or Pfizer vaccine.

Samples were analysed from 27 vaccinated individuals: 11 with COPD and 16 healthy; and 43 pre-vaccinated individuals:  24 with COPD and 19 healthy.

COVID-19 vaccines work in slightly different ways, but all expose our immune system to the spike protein of SARS-CoV-2, which coats the virus particle and is essential for infecting our cells. Immune responses to the vaccine spike protein were analysed, including levels of IgG and IgA antibodies, and T-cell responses.

Both vaccinated COPD patients and healthy individuals had higher anti-spike protein IgG antibody levels in plasma and airways compared to unvaccinated COPD patients and healthy individuals, with the level of vaccine-induced responses being similar in COPD patients and healthy subjects.

Dr Thomas Southworth, Honorary Research Associate at The University of Manchester and Senior Scientist at the Medicines Evaluation Unit Ltd said: “The results of this study will be a great relief for patients with COPD who can rest assured they can derive protection from COVID-19 vaccination, despite an impaired immune system.

“Vaccination did not induce a sustained IgA antibody response in the airways of either COPD patients or healthy subjects. IgA antibodies act to block viral infections as they initially enter our nose and airways.

“Future vaccines, which do induce sustained anti-SARS-COV-2 IgA antibody  responses in the upper airways, may offer additional protection for both COPD patients and healthy individuals equally.”

&�Բ�����;‘Airway immune responses to COVID-19 vaccination in COPD patients and healthy subjects’ is available

The team from The University of Manchester and Imperial College London analysed the relative effects of different non-pharmacological interventions aimed at controlling the spread of Covid-19. The study is published in BMC Public Health.

Of the nine interventions they examined, only closing schools and closing workplaces had a significant association with a decline in early Covid-19 attributed death rate.

Closing schools reduced mortality by 1.23 daily death per million over 24 days and closing workplaces reduced mortality by 0.26 daily death per million over 24 days.

For the UK, with a population of about 67 million, this would translate to roughly 82 and 17 daily Covid-19 deaths, respectively.

The main analysis used a mean score of strictness and timeliness for each intervention, to incorporate the full exposure of each country to each intervention.

However, examining strictness of interventions alone, stricter international travel controls, and timing of interventions alone, later restrictions on gatherings (when tighter restrictions were implemented), were also associated with lower Covid-19 mortality but only marginally.

Other interventions, such as stay-at-home orders (‘lockdowns’) or restrictions on public transport, were not significantly associated with differences in mortality rates across countries in the period of analysis after controlling for other interventions.

The team used sophisticated statistical modelling to generate 3,250 observations describing the association of an intervention with daily deaths per million over the next 24-days, the average estimated time between virus transmission and death.

To reduce study bias, they compared interventions implemented in the period before the first Covid-19 death, when policymakers wouldn’t have been able to react to deaths that had already occurred, and 14-days-after the first Covid-19 death, when numbers were still low and bias could still be minimised.

Lead author Dr Jonathan Stokes said: “There have been many policies enacted by Governments around the world to control Covid-19 transmission.

“Many of them can have some impact on reducing virus transmission, though they can also hurt our mental health and the economy.

“However, their relative impact on Covid-19 mortality is less clear, and that makes it harder for policy makers to create the maximum benefit with the minimal disruption.

“The way these interventions were rolled out, non-randomly and frequently multiple interventions in tandem, makes it extremely difficult for any single study to give a definitive answer on effectiveness of each.”

He added: “However, our study contributes to the growing literature and our clear finding was that schools and workplaces were linked to lower mortality in the early period. of the pandemic.  We’re not saying schools and workplaces should close but rather, policy makers might build these insights into their subsequent pandemic strategies in the future.

“With Covid-19, the school environment itself was lower risk due to the age profile of mortality effects, but might present a higher risk in terms of driving up community transmission of COVID.

“Schools and workplaces also represent places where compulsory social interactions occur, rather than voluntary ones such as going to a restaurant or pub, which a high-risk individual (for example, an older person, or person with existing medical conditions) might choose to avoid.

“Other research has also suggested this large voluntary mechanism, where community mobility rates have been shown to have fallen before interventions, such as stay-at-home orders, were even implemented, and mobility fell in comparable amounts in US counties without stay-at-home measures compared to those with.

“So perhaps focusing on interventions to reduce social interactions in ‘compulsory’, not ‘voluntary’, settings appears to have been the most effective strategy to mitigate early Covid-19 mortality.”

The study was based on data from early on in the pandemic, necessary to mitigate bias in the results, so it is not possible to speculate what these relative effects might have been in the second or subsequent waves. Behavioural responses might not have been the same as they were to the initial shock of the pandemic.

The paper ‘The relative effects of nonpharmaceutical interventions on wave one Covid-19 mortality: natural experiment in 130 countries’ is available

The paper is available to view in .

The study by University of Manchester epidemiologists, published in the reveals 5.78% of the over-90s were lost to the disease.

In Sweden the figure was 3.82%, Italy 3.18%, Germany 2.46% and France 2.08%. In the Netherlands, the figure for the over 95s was 3.87%.

A substantial increase in deaths in care homes in England and Wales in the first three months of the pandemic - estimated by other researchers at 79% - is likely to have contributed to the figure , argue the team.

Other studies have also shown that fatality in UK care homes was 270-300 times worse than  Australia, which has a similar health care system, demographics and care home settings – implying that the different approach to COVID-19 measures, particularly at the start of the pandemic, could be a contributory factor to this high death rate.

In terms of overall COVID-19 deaths per 1,000 people, South Korea had the lowest at 0.04, but England and Wales again had the highest at 2.39.

The study also showed in some countries, the relatively young had high rates of years of lives lost (YLL)- a measure of premature death.

YLL calculations take into account the remaining life expectancy that someone would have been expected to achieve had they not died at that age.

In the United States the figure was 9 YLL per 1,000 people in the under 50s, higher than the other 19 countries in the study.

Moldova (8.49 per 1,000), Romania (7.2 per 1,000) and the Ukraine (5.72 per 1,000) - the only 3 countries in the study classified as low or middle income – had the next largest YLL in the under 50s.

The study was carried out by extracting population statistics and cumulative COVID-19 death data from the National Institute for Demographic Studies’ Demography of COVID-19 Deaths database.

Greg Williams, who led the study said: “It is widely acknowledged that the risk of mortality from COVID-19 increases with age, with the highest death rates amongst older age groups.

“As a novel disease, it is reasonable to suggest that deaths from COVID-19 occur earlier than would otherwise have happened, even for the older populations.

“But most mortality measures use an upper endpoint for defining when a death is premature, such as 70 or 75 years of age.

“We argue there is a considerable burden of premature mortality within much older age groups who have died as a result of COVID-19 too, particularly in England and Wales when compared against the other countries in our study.

“Due to the different ways countries record and collect their data, the figure in the paper looks at the over 90s whereas other countries don’t have this age category. However, when we lowered the age category to 75 and 80 years and over, England and Wales still had the highest deaths as a proportion of that population.

“For 80 years and over, this was 2.86% of the population, with Italy the next closest with 1.75%, and for 75 years and older, this was 2.09% with Belgium the next highest at 1.94% of the population.

“That implies the difference in approaches to lockdown and other measures could have been a contributory factor to the higher death rate in these age groups.

“Whatever your age and wherever you live, your life should be valued. The approach of this study values all life equally wherever you are from. It’s important for decision makers to compare what is happening locally with other places around the world to ensure they are not inadvertently accepting inequalities felt locally.”

Professor Arpana Verma, a co-author of the paper, said: “This approach towards understanding COVID-19 mortality provides an alternative narrative to recognise how different countries have coped with the reality of the pandemic.

“This compares what actually happened with how they were expected to cope through approaches such as the Global Health Security Index, which found in 2019 that the United States and the United Kingdom were the two most prepared countries for an epidemic or pandemic.”

The findings, published in PLoS Medicine ,  overturns the prevailing view that ethnic inequalities in Covid-19 vaccine uptake simply follow previous trends in people’s willingness to take up vaccination.

Instead, the researchers suggest, the Covid-19 vaccination programme has created additional and different inequalities beyond pre-existing inequalities in vaccine uptake.

Adjusting for age and clinical vulnerability, people from Arab, mixed White and Black African, mixed White and Black Caribbean, and all Black or Black British backgrounds were less than half as likely to take up Covid-19 vaccination compared to the White British group.

Inequalities in Covid-19 vaccine uptake were at least double the size of flu vaccine inequalities for almost half (7/16) of ethnic minority groups.

Differences between the two types of vaccine were particularly stark for those from a Bangladeshi background.

After adjusting for age and clinical vulnerability, people belonging to the Bangladeshi group were almost 10% more likely to have taken up flu vaccination, yet over 40% less likely to have taken up the Covid-19 vaccine, compared to the White British group.

Most worryingly, ethnic inequalities were highest amongst people at the highest risk of severe Covid-19 – older and more clinically vulnerable people, and those living in the most income-deprived areas.

The researchers examined 752,715 people eligible for the Covid-19 vaccine between December 2020 and April 2021, and the flu vaccine between September 2019 and March 2020.

“We found ethnic inequalities in Covid-19 vaccine uptake are far wider than those seen previously for seasonal Influenza vaccine, and exist even among those recently vaccinated against Influenza,” said lead author Dr Ruth Watkinson from The University of Manchester.

 “Further research and community engagement is needed to build trust and confidence amongst minority ethnic communities, and to better understand and remove barriers to vaccine access.”

Online public discussion groups with diverse members of the Greater 91ֱ�� community identified themes which could explain the inequalities.

Stephanie Gillibrand, another 91ֱ�� researcher involved in the study said: “Existing mistrust stemming from racism, experiences of culturally insensitive healthcare, and awareness of previous unethical healthcare research were all themes raised in discussion groups.

“concerns about potential unknown side-effects of Covid-19 vaccines compared to existing vaccines may have been heightened among people from minority ethnic groups due to their underrepresentation in Covid-19 vaccine clinical trials.”

“Additional research is required to further explore the complex social, political and structural drivers and barriers to vaccine uptake which drive these statistics, as highlighted by our public engagement work”

Nicolas Filer, a public contributor involved in the study said: “Especially interesting was the clear exposure of differences in vaccine uptake within different ethnic minority groups and communities within the broader widely used classifications.

“Once the more special needs of some of our community were recognized and responded to by the NHS, their vaccine take up was greatly increased.”

Dr Watkinson added: “Even for healthcare services provided free at the point of use, disadvantaged populations with the greatest ‘need’ for care tend to have lower uptake of services.

“Residential segregation driven by systemic racism may have resulted in barriers - in terms of journey time and cost - to accessing large centralised vaccination sites for some communities.

“However, local solutions such as vaccine pop ups and local centres have now expanded vaccine access across Greater 91ֱ��. These innovations, alongside providing culturally-sensitive vaccination options, are crucial for equitable access.”

Issues around racism were raised in the discussion groups. Some people from ethnic minority backgrounds reported difficulties booking and traveling to vaccination appointments, as well as a lack of official vaccine information translated into additional languages.

While Covid-19 vaccines were initially only available at booked appointments in mass vaccination centres, flu vaccines are available through GP practices and community pharmacies, which often operate drop-in services and are more accessible in areas of high deprivation.

The research team recognise the partnership of Greater 91ֱ�� Health and Social Care Partnership, Health Innovation 91ֱ�� and Graphnet Health, on behalf of GM localities in the provision of data required to undertake the work. This work uses data provided by patients and collected by the NHS as part of their care and support.

The paper Ethnic inequalities in Covid-19 vaccine uptake and comparison to seasonal Influenza vaccine uptake in Greater 91ֱ��, UK: a cohort study is available here

The University of Manchester, and the study, published in Frontiers of Public Health today (22/2/22), shows that symptoms – which by definition are not measurable – are a fertile ground for misinterpretation.

The study was supported by . Funding was received from 91ֱ�� BRC, the , the and Neuromod Devices Limited.

Reports of associations between COVID-19 and auditory symptoms such as hearing difficulty and tinnitus have been widely discussed in the media and academia.

However, most studies have relied on self-reporting and lacked baseline information from before the pandemic.

That makes it difficult to know whether symptoms occurred because the COVID-19 virus affected the ear itself, or whether they occurred because of psychosocial factors like living through a pandemic, fears about what the virus might do, or recall bias.

In a YouGov poll in 2019 of over 10,000 people, Professor Chris Armitage, Chair in Health Psychology at the University of Manchester, and 91ֱ�� BRC Hearing Health, Optimising Outcomes Programme Lead, asked, among other things, whether people had hearing difficulty and/or tinnitus.

In August 2021 the current study team commissioned YouGov to contact the same people about symptoms they had experienced during the pandemic and 6,881 responded.

The second survey asked about the onset and change in three types of symptoms:

• ·Type one: loss of smell, memory/concentration issues, persistent fatigue which have known association with COVID-19.
• ·Type two: auditory symptoms (hearing difficulty and tinnitus) which have an indeterminate association with COVID-19.
• ·Type three: toothache, a red herring with no established association with COVID-19.

Although there were twice as many reports of new hearing difficulties and tinnitus in people with confirmed and suspected COVID-19,compared to people who hadn’t had COVID-19, they found:

• The onset of new auditory symptoms coincided with COVID-19 in only a third of the people reporting the symptoms; a third didn’t know when their symptoms began; and a third said their symptoms began before the pandemic, even though all had said they didn’t have auditory symptoms in March 2019.
• More than 60 per cent of people with confirmed or suspected COVID-19 said that their toothache had also been affected by COVID-19 despite there being no evidence of an association.
• As expected, Type one symptoms were reported most commonly by the people with confirmed COVID-19. But Type two and Type three symptoms were reported most commonly by the people who suspected they had COVID-19.

The study also asked about challenges experienced during the pandemic, such as feeling lonely and anxious, lack of exercise, lack of space at home, caring for others.

They looked at the number of challenges reported relative to the number of symptoms experienced during the pandemic and found the higher the number of challenges, the more symptoms were reported.

Dr Gabrielle Saunders from The University of Manchester, who manages ,  was lead author on the study. She said: “Although there were more reports of auditory symptoms in people with confirmed or suspected COVID-19, our study provides evidence that psychosocial factors influenced what our respondents felt.

“We also found that respondents were inconsistent with their reporting of hearing symptoms over time. We think this is in part because their answers were affected by the context in which the question was asked.

“Even if the symptoms arose due to psychosocial factors, they are still real to the person experiencing them and so need to be managed – but using different therapeutic strategies than if they were directly caused by the virus.

“That is why we need to take great care in attributing any symptom to the effect of the virus, especially if we lack baseline data.

“We feel that studies which include control groups and use audiometric measures (hearing tests) in addition to self-reporting, to investigate change in auditory symptoms relative to pre-COVID-19, are urgently needed.”

The study vividly depicts health inequalities in terms of excess years of life lost – a measure of premature mortality measuring the extra years lost during the pandemic compared with previous years.

The measure, the first time it has been used in the context of Covid-19, accounts for both the number of deaths and the age at which those deaths occurred and allows comparison between causes of death across population groups.

Published in PLOS Medicine, one of the world’s leading journals, the study shows that the most deprived areas reported much higher numbers in excess years of life lost, even after adjusting for population size. Excess years of life lost per 100,000 population ranged from 916 for the least deprived quintile to 1,645 for the most deprived.

And there was also marked variability in both Covid-19 related and all-cause excess years of life lost by region, with the highest rates in the North West of England, which was three times as high as those in the South West of England.

Between March 2020 and December 2020, there were an estimated 763,550 excess years of life lost, equivalent to a 15% increase compared to the equivalent time period in 2019. 85% of the deaths were directly attributed to COVID-19 or another respiratory disease.

The impact of deprivation on mortality was greatest in younger people: for all-cause mortality in the most deprived areas, 15 to 44 year olds were estimated to have had 480 excess deaths, compared to 42 in the most affluent, or over 11 times as many. Adjusting for population sizes, ratios of all-cause excess deaths ranged from 2.7 in 15 to 45 year olds to 1.6 in those aged 85 or over.

For mortality caused directly by COVID-19 and respiratory illness, in the most deprived areas, 15 to 44 year olds were estimated to have had 268 excess deaths, compared to 51 in the most affluent, over 5 times as many. Adjusting for population size, ratios of Covid-19 excess deaths ranged from 5 in 15 to 45 year olds to 1.6 (again) in those aged 85 or over.

More years of life were lost for men on average, 10.5 in COVID/respiratory deaths and 10.8 in all-cause deaths, compared to 9.5 and 8.2 for women, respectively.

The pandemic exacerbated longstanding socioeconomic inequalities, with the ratio of observed years of life lost for the most deprived fifth of areas compared to the most affluent increasing from 1.56 in 2019 to 1.64 in 2020.

Professor Evan Kontopantelis from The University of Manchester said: “The pandemic widened pre-existing health inequalities across England and Wales: regions and social groups with the highest baseline mortality rates experienced the greatest impact on years of life lost.

“Linked to this, we think the impact of the pandemic may have been higher than previously thought on the most deprived areas of England and Wales, with more younger people dying directly or indirectly from COVID-19 in these areas.”

Professor Tim Doran from the University of York said: “Our findings support the notion that Years of Life Lost can be more informative for determining unmet needs and informing policy for this or future pandemics.

“In particular, it could provide vital information to aid the targeting of vaccines, financial aid and social support during this and future pandemics.”

The paper Excess years of life lost to COVID-19 and other causes of death by sex, neighbourhood deprivation and region in England & Wales during 2020: a registry is published in PLOS Medicine

The study, published in the journal , was conceived and conducted at The University 91ֱ�� and led by Ling Tan, a visiting scientist at the . The team started with 158 studies that were published early in the pandemic using data before November 2020.

Because many viral respiratory diseases show seasonal cycles, weather conditions could affect the spread of COVID-19. Although many studies tried to examine this possible link, their results were often inconsistent.

Tan performed meta-regression analysis on the data from previously published articles to make sense of this large body of data derived from locations all around the world, using inconsistent research methods, and using a variety of different datasets with varying study quality. The results were exceptionally revealing.

From this large dataset, the team found several principal findings, including that 80 of the 158 studies did not state the time lag between infection and reporting, rendering these studies ineffective in determining the weather–COVID-19 relationship.

The data also showed Asian countries had more positive associations for air temperature than other regions, possibly because the temperature was undergoing its seasonal increase from winter to spring during the rapid outbreak of COVID-19 in these countries showing how correlation does not necessarily imply causation. Higher solar energy was also associated with reduced COVID-19 spread, regardless of statistical analysis method and geographical location.

Lead author Ling Tan said: “The public generally believes that there is a negative relationship between temperature and COVID-19, such as the higher the temperature, the slower the spread of the pandemic. However, previous studies did not consistently get this result. We found two reasons for this. First, most of these studies use a simple analysis approach called linear regression, which would produce a straight line for all temperatures. But, the stability of the virus may be maximum at moderate temperatures, for example; very low and very high temperatures may make the virus inactive, for which linear regression would be an inappropriate analysis.”

“Second, the rapid outbreak of the COVID-19 pandemic in some countries in the early stages would overwhelm the more subtle weather effects. Thus, we recommend that future studies use nonlinear regression models to capture the association between weather and COVID-19."

Professor David Schultz, who was a co-author on the study said: "What was most surprising to me was that over half of the studies we examined (80 out of 158) did not say that they accounted for the time lag between the weather on the day the people were infected and the day when their COVID-19 illness was reported. We know this could be as much as two weeks. Thus, these studies were either poorly designed or poorly communicated. Thus, we had to throw these studies out of further analysis because we couldn’t trust their results.”

The results from the meta-regression analysis surprised the researchers who began to see links with sunlight on the virus spread. “We were able to show across these remaining 78 studies that higher solar energy was associated with reduced COVID-19 spread, regardless of statistical analysis method and the geographical location of the study, possibly due to the benefits of ultraviolet radiation and vitamin D on reducing COVID-19 spread or because sunlight inactivates the virus.” said Professor Schultz.

This research also suggests best practices that should be considered in future studies of disease and weather conditions.

A link to the full article can be found here:

The research**, published in The Journal of the American Medical Association Network Open (JAMA Network Open) today, was funded by the National Institute for Health Research Greater 91ֱ�� Patient Safety Translational Research Centre (NIHR GM PSTRC). The Centre is a partnership between The University of Manchester and The Northern Care Alliance NHS Foundation Trust.

The study found there was an almost six-fold increase in the likelihood of reporting fatigue to a GP following a positive PCR test and a threefold increase in the risk of sleep problems compared to those without a positive test, for people who haven’t previously visited their GP for any of these reasons in the past.

There was also an 83% increase in mental illness following a positive PCR test. However, there was also a 71% increase in the risk of mental illness for people who received a negative PCR test compared to the general population. Researchers believe this throws some doubt about whether COVID-19 is directly causing mental illness, because it is clear that those who get a test are more likely to have risk factors for mental illness, for example pandemic-related anxieties.

Dr Matthias Pierce, researcher at The University of Manchester who led the work, said: “When we began this research project we wanted to investigate whether we could find any evidence in primary health care records that COVID-19 was linked to an increased risk of mental health illness, sleep and fatigue problems.

“While fatigue is clearly a consequence of COVID-19 the risk of experiencing sleep problems is also very high. However, we are sceptical regarding the extent that COVID-19 is directly causing people to become mentally ill, or whether those with a predisposition to mental illness are more likely to get tested.”

Professor Roger Webb, from The University of Manchester, who co-leads the Mental Health research programme at the NIHR GM PSTRC, said: “Our findings align with those generated by investigations conducted in other countries in revealing elevated risks of mental illness, self-harm, fatigue, and disrupted sleep patterns among people testing positive for infection during the pandemic. Establishing the mechanisms that have caused these outcomes to occur is the next major challenge for researchers in our field.”

Professor Carolyn Chew-Graham, a co-author on the paper, Professor of General Practice Research at Keele University and a General Practitioner, said “It is vital that general practitioners recognise the long-term impact of COVID-19 infection on their patient population. Offering follow-up to people who test positive for COVID-19 infection may help identify persisting symptoms, and sign-post people to the . The increased risk of developing mental health problems in people who tested negative may be due to health anxiety in these patients, and primary care has a role in identifying and supporting such patients.”

* Clinical Practice Research Datalink (CPRD-Aurum) dataset: a large UK primary care registry covering 19 million patients. It contains information on clinical events recorded by healthcare professionals, including diagnosis, symptoms and therapies.

** Is infection with COVID-19 causing an increased risk of psychological distress, psychotropic prescribing or sleep and fatigue problems? A study of patients in English primary care

Researchers from (MIB), led by Professor Nicholas Turner, Dr Sarah Lovelock and Professor Anthony Green, have developed an efficient biocatalytic manufacturing route to Molnupiravir. Experimental work was led by Dr Ashleigh Burke who developed a new enzyme, cytidine aminotransferase, to allow the production of a key Molnupiravir intermediate.

The unique approach of the 91ֱ�� team is currently being further developed with industrial partners at multi-Kg scale to enable adoption by generic pharmaceutical manufacturers at large scale.

Professor Anthony Green said: “We are hopeful that our work will contribute to the challenge of developing a low-cost manufacturing route to Molnupiravir to allow the widest possible access to this promising COVID-19 therapy.”

The research undertaken by The University of Manchester team has been to allow pharmaceutical manufacturers around the world to take advantage of this development.

Sterling Pharma Solutions, a pharmaceutical contract development and manufacturing organisation (CDMO), has been engaged to support scale-up development and manufacturing activities utilising the novel enzyme developed by the 91ֱ�� team. Sterling’s CEO, Kevin Cook, said: “We are incredibly proud to be working in partnership will all those involved to help improve global access to what looks to be a very promising, life-saving treatment.”

In order to maximise the impact of the new enzyme technology, Prozomix Ltd, a biocatalyst discovery and contract manufacturing organisation (CMO), will employ foundation funds to produce high-quality cytidine aminotransferase and distribute it globally free-of-charge. Any company can obtain a sample by emailing Molnupiravir@prozomix.com.

Prozomix's Managing Director, Professor Simon Charnock, said: "Establishing a new and widely employable biocatalytic route for an API has arguably never been as urgent, we feel most privileged to play our part in this collaboration."

Initially involving participants aged 60+, its creators say the drug - called GRT-R910 – can boost the immune response of first-generation COVID-19 vaccines to a wide array of variants of Sars-Cov-2, which cause COVID-19.

The trial will take place at the NIHR 91ֱ�� Clinical Research Facility at 91ֱ�� Royal Infirmary, part of Manchester University NHS Foundation Trust (MFT).

At MFT, the trial is being delivered by the Research and Innovation Vaccine Team. Andrew Clarke(63), was the first to receive the jab followed by his wife Helen (64). Both are retired, from Bolton.

Also supported by Health Innovation 91ֱ��, the trial is expected to recruit 20 volunteers, with data evaluating the vaccine expected in the first quarter of 2022. Results from the preclinical studies leading up to the development of the vaccine will be jointly published by Gritstone and the National Institutes of Health later in the year.

Part of Gritstone’s CORAL program, GRT-R910 is a self-amplifying mRNA second generation SARS-CoV-2 vaccine – or SAM for short, which delivers antigens from both the spike and non-spike proteins.

SAM vaccines, say its creators, may offer the opportunity of lowering vaccine doses or eliminate the need of repeat administrations – with the potential to safely drive strong, durable and broad immune responses across SARS-CoV-2 variants.

SAM vaccines work by inducing special immune cells (CD8+ T cells), an important arm of the body’s immune response to viruses, as well as antibodies that can neutralise the virus and prevent it binding to and infecting cells. It is hoped that this will offer potential for robust and persistent immunity, which includes at-risk and older populations.

“Our SAM COVID-19 vaccine is designed to drive robust CD8+ T cell responses, in addition to strong neutralising antibody responses, offering the promise of longer lasting immunity,” said Andrew Allen, M.D Co-Founder, President and Chief Executive Officer of Gritstone.

He added: “Since viral surface proteins like the spike protein are evolving and sometimes partially evading vaccine-induced immunity, we designed GRT-R910 to have broad therapeutic potential against a wide array of SARS-CoV-2 variants by also delivering highly conserved viral proteins that may be less prone to genetic variation in the virus.

“Our hypothesis is that a different vaccine such as GRT-R910 might complement the primary immune response from pre-existing vaccination with a first generation COVID vaccine in such a way that it would provide more benefit than an additional dose of the same vaccine.”

Professor Andrew Ustianowski, who is Clinical Lead for the NIHR COVID Vaccine Research Programme, Consultant in Infectious Diseases and Tropical Medicine at North 91ֱ�� General Hospital (part of MFT) and Honorary Clinical Chair at The University of Manchester, will be the local lead investigator for this study. Professor Ustianowski is Chief Investigator for the study and MFT is the chief site.

He said: “We now know the immune response to first generation vaccines can wane, particularly in older people. Coupled with the prevalence of emerging variants, there is a clear need for continued vigilance to keep COVID-19 at bay.

“We think GRT-R910 as a booster vaccination will elicit strong, durable, and broad immune responses, which are likely to be critical in maintaining protection of this vulnerable elderly population who are particularly at risk of hospitalisation and death.”

Professor Ian Bruce, from The University of Manchester, is Chair of the 91ֱ�� COVID-19 Research Rapid Response Group (RRRG) , Consultant Rheumatologist at The Kellgren Centre, 91ֱ�� Royal Infirmary, Academic Director at Health Innovation 91ֱ�� and Director of the NIHR 91ֱ�� Biomedical Research Centre.

He said: “We’re tremendously excited that this promising vaccine is to be trialed here in 91ֱ��. As the only European site for this study, it is testament to the way our academic and clinical researchers have come together as part of the ‘One 91ֱ�� R&I’ approach to answer the questions the world needs answers to.

“Though the vaccine is being trialled in the over 60s, future studies will also examine its efficacy in other-vulnerable populations.

“If successful, we feel it has the potential to have play a significant role in the battle against COVID-19, which has so devastated vulnerable populations across the globe.

“We look forward to working with Gritstone in the clinical development of this promising next generation COVID-19 vaccine.”

The study will examine dose, safety, tolerability, and immunogenicity of GRT-R910 at two dose levels at least four months after the second administration of their initial vaccine.

GRT-R910 is also being investigated as part of a US National Institute of Health sponsored Phase 1 study.

Additional trials of the CORAL platform, including an additional Phase-1 trial are also planned, which will inform the future development of CORAL, Gritstone’s SARS-COV-2 second generation vaccine programme.

Andrew Clarke, said: “We signed up to the NIHR COVID-19 Vaccine Registry last summer as we had a general desire to be helpful.”

Helen Clarke said: “I used to work in the NHS and had been involved in research as a nurse in the past.

“We’ve been amazed how quickly a vaccine was made and approved and that couldn’t happen without volunteers.”

Andrew added: “Somebody has to be the first and we’re confident in the science and technology behind this vaccine and convinced of the need for it.

“Because we’re both retired, we feel we had a reasonably easy lockdown, but we know it wasn’t the same for everybody. We feel that this is perhaps a small part we can play in helping to make things change.”

Published in the journal the 34 patients, carers and clinical staff were interviewed by a team of researchers from The University of Manchester.

The study was funded by the National Institute for Health Research Greater 91ֱ�� Patient Safety Translational Research Centre (NIHR GMPSTRC).

NIHR GMPSTRC is a partnership between The University of Manchester and Salford Royal NHS Foundation Trust.

Mental health service users also reported ‘working harder’ to avoid admission due to fears around environmental safety as a result of COVID-19.

“Even before the pandemic, there are lots of safety concerns associated with recent discharge from inpatient mental health services, for example suicide and self-harm,“ said lead author Dr Natasha Tyler, researcher at the GM PSTRC and The University of Manchester.

Dr Tyler added: ‘Our patients and carers felt that because of  the national need to free-up hospital beds, the quality of discharge and admission planning was compromised at times.

“That meant discharging patients from hospitals who were not ready to cope in the community or not admitting patients who needed in-patient care.

“The closure of most community support services meant patients had minimal opportunities for accessing care via alternative routes. This worsened their feelings of helplessness and loneliness.”

However, co-author Dr Maria Panagioti, from The University of Manchester and NIHR GM PSTRC said there were some positive outcomes during the first lockdown:

Dr Panagioti said: “Despite some distressing findings, there were rapid changes in acute care, some of which resolved long-standing problems about patient safety.

“Virtual meetings, for example, enabled interdisciplinary teams and agencies to jointly discuss patient discharge which was often considered unrealistic prior to the pandemic.

“They also improved patients’ attendance by eliminating barriers such as travelling complications and social phobias.”

Co-author Andrew Grundy who has also used mental health services said: “Having personally lived through transitions from inpatient to community services myself, I know how worrying and how stressful this time can be, and COVID-19 has only added to these pressures.

“Our study sheds further light on service users’ own ‘safety concerns’ around rapid discharge, difficulties in accessing community services post-discharge, and feelings of loneliness and social isolation post-discharge, which they have experienced as a direct result of the first national lockdown.”

The paper Effects of the first COVID-19 lockdown on quality and safety in mental healthcare transitions in England is available

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The team led by University of Manchester scientists  used the drugs to treat liver and kidney cells, which are commonly targeted by the virus in patients with severe disease.

Another 27 drugs also reduced replication in cells when treated prior to SARS-CoV-2 infection in the study published in the journal PLOS Pathogens and funded by Wellcome and approved by the COVID-19 Rapid Response Group at the University.

The eight drugs include the antimalarials Amodiaquine and Atovaquone; Bedaquiline which treats TB and Ebastine which treats allergic rhinitis and urticaria.

They also include Abemaciclib and Panobinostat which treat cancer, Manidipine, an antihypertensive, and vitamin D3, a health supplement bought over the counter.

“Our study has identified strong candidates for drug repurposing, which could prove powerful additions to the treatment of COVID-19,” said Dr. Adam Pickard, who is an early career researcher with Professor Karl Kadler from The University of Manchester, who led the study.

Dr Pickard said: “Our identification of repurposed drugs that can stop SARS-CoV-2 replication could have enormous utility in stemming the disease.

“As these drugs are FDA-approved and with a safe dosing regime already established for use in patients, clinical trials could be initiated for these drugs within a relatively short time frame.

“The high costs and lengthy lead-in times associated with new drug development, make repurposing of existing drugs for the treatment of common and rare diseases an attractive idea.

“But we strongly urge patients taking these medications not to self-treat and that their doctors are best placed to advise how to manage their condition.”

The scientists used a version of the virus which was tagged with a protein allowing it to glow for easy identification.

They evaluated a range of human cell types for their ability to be infected and support replication. A luminescent enzyme called nano-luciferase was used to measure virus replication.

Professor Kadler added: “The different stages of the disease, from the initial infection of host cells through to virus replication and the response of the immune system, offer opportunities to identify drugs, treatments and therapies to help stop disease progression.

“Large proportions of the world’s population remain at risk of contracting COVID-19 as they wait to be vaccinated.

“So the identification of safe and easily distributed medications that can target the different stages of virus infection and replication, could reduce the spread of SARS-CoV-2 and reduce the cases of COVID-19.”

The multiple steps involved in virus infection and proliferation, could mean that  the drugs may have different molecular targets; for some, additional targets are still being clarified.

More on some of  the drugs identified in the study:

• Panobinostat, is a HDAC inhibitor that blocks DNA replication, and has been used to inhibit cell growth in the management of cancer. Panobinostat had the strongest effect on limiting SARS-CoV-2 replication whilst maintaining cell viability, and completely blocked replication of SARS-CoV-2 at all doses tested (Figure 5); however, if cells were infected prior to treatment a more modest effect on replication were observed
• Atovaquone has been identified in other studies of SARS-CoV-2 in the context of COVID-19. It is a hydroxynaphthoquinone approved by NICE for the treatment of mild to moderate pneumocystis pneumonia and as a prophylaxis against pneumocystis pneumonia. Research has suggested potential binding of atovaquone to the SARS-CoV-2 spike protein.
• Ebastine treats allergic rhinitis and chronic idiopathic urticaria and vitamin D3, is a health supplement available over the counter. The ability of  vitamin D supplementation to reduce the risk of SARS-CoV-2 infection or COVID-19 severity is unclear. In this study, vitamin D3 met the stringent cut-offs of 85% virus reduction.

The paper Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells is published in PLOS Pathogens and is available 

The patients in the study, whose frailty and other medical conditions meant they were unlikely to benefit from invasive mechanical ventilation and intensive care treatment, received treatment with either an oxygen mask or CPAP.

The study of CPAP was led by researchers at The University of Manchester and , and is published today (insert date) in the Lancet’s EClinical Medicine.

Though the study team argue more research is needed to confirm the findings and see if there are specific groups of patients who may benefit from CPAP, the research, they say, casts doubt on current national and international guidance that supports broad application of the treatment.

All the 479 patients from seven NHS Trusts across the North West of England had both respiratory failure from COVID-19 and pre-existing medical conditions which meant invasive mechanical ventilation in intensive care would not help them.

Overall CPAP did not improve mortality: 75.6 per cent of the patients died after 30-days in the oxygen group (186/246 patients) whereas the figure was 77.7 per cent in the CPAP group (181/233 patients).

In the study, almost 50 per cent of the patients on CPAP – in which oxygen under pressure is delivered through a tight-fitting mask under pressure - chose to discontinue the therapy after around two days.

The clinicians involved say that might be because patients felt they did not feel benefit from the treatment, they found it hard to tolerate, or other reasons.

The study team hope the results can help clinicians guide patients to make informed, joint decisions, about whether to give CPAP treatment. Until now, there had been no information comparing CPAP to oxygen therapy.

The data adds to a recent national study which looked at otherwise healthy patients, excluded from the 91ֱ�� study, requiring oxygen who were likely to benefit from invasive mechanical ventilation and ITU treatment.

The study of the different patient group, not looked at by the 91ֱ�� team, is available as a pre-print and summarised in the , found CPAP reduces the need for invasive mechanical ventilation in the fitter COVID-19 patients.

That – together with the results of the 91ֱ�� study - suggest CPAP – which requires high dependency care but can be delivered on a ward, might be more effectively used for otherwise healthy patients, freeing up beds in intensive care units.

Dr Laurence Pearmain, a clinical researcher at The University of Manchester and a respiratory doctor at Wythenshawe Hospital, part of , and funded by the Medical Research Council (MRC), led the study.

He said: “CPAP therapy is commonly used for patients with respiratory failure from severe COVID-19 pneumonitis, including in patients not likely to benefit from invasive mechanical ventilation.

“But we show there is no evidence to demonstrate its superiority over conventional oxygen therapy in those patients.

“High patient-initiated discontinuation of CPAP suggests it can be a significant treatment burden for them; it’s fair to assume that CPAP is a stressful experience for some patients. Conventional oxygen therapy, delivered by a mask is far easier to tolerate.

“Our study findings, including the absence of a clear benefit from CPAP in this frail patient population, can help inform often challenging conversations between patients and doctors when making treatment decisions surrounding breathing support.

“Ward-level delivery of CPAP also presents practical challenges to nursing staff, however, for some patients CPAP is a valuable and effective treatment when used in the correct context.”

Co-author, Dr Tim Felton, is Clinical Senior Lecturer at The University of Manchester, researcher at the and Consultant in Intensive Care and Respiratory Medicine at Wythenshawe Hospital.

He said: “We feel that reflection is warranted on the current treatment guidance and widespread application of CPAP for these patients who cannot be treated with mechanical ventilation.

“Given the resources required to provide CPAP, it raises questions as to whether it should be provided to patients who are not suitable for mechanical ventilation, which has been commonplace during the COVID-19 pandemic.

“Some caution should be applied to these findings, as there may be patient sub-groups who benefit from CPAP in the setting of COVID-19. There have been no studies looking at predictors of CPAP efficacy in this patient cohort to date, and our study was not designed to address that question.”

Dr Patrick Bradley is an author and co-lead of the North West Collaboration Organisation for Respiratory Research (NWCORR) research network as well as a respiratory doctor at , who provided statistical support for the study.

He said: “This project is a great example of what can be done when research-interested doctors from around the region work together, gathering much more data than any single hospital could do on their own. It has added meaningfully to our understanding of an important, unanswered question.”

The study was co-ordinated through the North West Collaboration Organisation for Respiratory Research (NWCORR) and included clinicians at 91ֱ�� University NHS Foundation Trust, Blackpool Teaching Hospitals NHS Foundation Trust, Lancashire Hospitals Teaching NHS Foundation Trust, University Hospitals Morecambe bay Teaching Hospitals NHS Foundation Trust and Wrightington, Wigan and Leigh NHS Foundation Trust.

The  paper Conventional oxygen therapy versus CPAP as a ceiling of care in ward-based patients with COVID-19: a multi-centre cohort evaluation is  published in

Around half of the increased COVID-19 mortality and two-thirds of the increased all-cause mortality were explained by preventable higher deprivation and worse pre-pandemic health in the North.

The report from the Northern Health Science Alliance, Policy@91ֱ�� and northern National Institute for Health Research Applied Research Collaboratives (NIHR ARCs), has laid clear the devastating impact of the pandemic on people across the North of England.

The report found:

• People living in the North had a 17% higher mortality rate due to COVID-19 than those in the rest of England. Their mortality rate due to all causes was 14% higher.

• About half of the increased COVID-19 mortality in the North and two-thirds of the increased all-cause mortality were explained by potentially preventable higher deprivation and worse pre-pandemic health.
• The North’s care home COVID-19 mortality was 26% higher than the rest of England.
• In the North 10% more hospital beds were occupied by COVID patients than in the rest of England.
• Increased mortality in the North of England could cost the national economy up to £7.3bn in lost productivity. This will likely to be a conservative underestimate given the North’s economy has also been hardest hit.
• On average people living in the North had 41 more days of the harshest restrictions than people in the rest of the country.
• The North experienced a larger drop in mental wellbeing, more loneliness, and higher rates of antidepressant prescriptions: there was a 55% increase in the presence of minor psychiatric disorders, such as anxiety and depression, in the North compared to a 50% increase in the rest of England.
• Wages in the North were lower than the rest of England before the pandemic and these fell further during the COVID-19 pandemic (from £543.90 to £541.30 per week) whereas wages increased in the rest of the country (from £600.80 to £604.00 per week).

• The unemployment rate in the North was 19% higher than the rest of England.

The COVID-19 pandemic has hit the country unevenly with a disproportionate effect on the North of England - increasing regional health and economic divides. The Northern Health Science Alliance commissioned the report to understand the impact of the first year of the COVID-19 pandemic on health and productivity in the North and identify the opportunities for levelling up regional health and productivity.

The report shows the unequal health and economic impacts of COVID-19 on the North with higher rates of COVID-19 related mortality and unemployment.

Report authors make a series of recommendations to Government including:

• Place-focused vaccination programmes targeted at vulnerable populations in the North of England.
• Increase NHS and local authority resources and service provision for mental health in the North. Invest in research into mental health interventions in the North.
• Invest in increasing capacity in northern hospitals to help them catch-up on non-COVID-19 health care.
• Make health a key part of an integrated levelling up strategy.
• Recommit to ending child poverty. Increase child benefit, increase the child element of universal credit by £20 per week, extend provision of free childcares, remove the benefit cap and the two-child limit and extend provision of free school meals. Invest in children’s services by increasing government grants to local authorities in the North.
• Maintain and increase the additional £1,000 extra funding of universal credit.
• Provide additional resource to local authorities and the NHS in the North by increasing the existing NHS health inequalities weighting within the NHS funding formula in its reset and restore plans.
• Deliver a £1bn fund ring-fenced to tackle health inequalities at a regional level and increase local authority public health funding to address the higher levels of deprivation and public health need in the North.
• Create northern ‘Health for Life’ centres offering a life-long programme of health and wellbeing advice and support services from pre-natal to healthy ageing programmes.
• Deliver health and mental health promotion interventions together with industry and employer, targeted at employee mental and physical health.
• Level up investment in health R&D in the North of England to create high value jobs and support local health and drive the economy. Invest in North’s testing and diagnostics infrastructure.
• Build resilience in the North’s population through developing a national strategy for action on the social determinants of health with the aim of reducing inequalities in health, with a key focus on children.

Dr Luke Munford of University of Manchester said: “The pandemic has hit us all hard in different ways, but our report shows that people living in the North were much more likely to be hardest hit, both in terms of health and wealth. The fact that over half of the increased COVID-19 mortality and two-thirds of all-cause mortality was potentially preventable should be a real wake-up call. We need to invest in the health of people living in the North to ensure they are able to recover from the devastating impacts of the pandemic.”

Professor Clare Bambra of Newcastle University said: “Our report shows how regional health inequalities before COVID have resulted in an unequal pandemic - with higher rates of ill health, death and despair in the North. The economic impact of the lockdown is also looking likely to exacerbate the regional economic divide. The government’s levelling up agenda needs to seriously address health inequalities in the North - for all generations.”

Health Inequalities lead for the Northern Health Science Alliance, Hannah Davies, said: “As we approach autumn with uncertainty around an expected increase in COVID19 cases and with increasing questions about what ‘Levelling Up’ will mean for the North of England it is clear significant action must be taken in tackling health inequalities.

“The Government has made clear its commitment to level up and to tackle health inequalities, this report shows the importance of making that a reality with significant funding to tackle ill health through significant investment into public health and the NHS in the North of England.”

Professor David Taylor-Robinson of Liverpool University said: "Even before the pandemic we were seeing extremely concerning trends in rising health inequalities with life expectancy going backwards, particularly for women in the most disadvantaged areas in the North of England - the same areas affected by rising poverty and cuts to services that support health.

“The pandemic arrived in the middle of this worrying scene and amplified existing inequalities. As outlined in this new report, poor populations in the North have been hit the hardest in terms of COVID related mortality, and our analysis shows that much of this is due to pre-existing deprivation and poor health. Building back fairer will require long term investment to address the root causes of poor health in the North."

When vaccination sites were set up across the country in December, there was an urgent call out for volunteers to quickly vaccinate as many people as possible. Working in collaboration with , the and , hundreds of students have stepped up to volunteer as stewards, translators, data inputters and vaccinators, playing a crucial role in the fight against COVID-19.

Maisie Camm, a final year Biomedical Sciences student who has been volunteering as a vaccinator for St John Ambulance said: “The first shift flew by and I absolutely loved it so I signed up for more. It has been a great opportunity for me and I’m very lucky to have had the chance to help people during this time.” 

Maisie is applying to study Medicine in the Autumn, and so her experience supporting the distribution of the vaccine was the perfect chance to learn new skills and chat with new people.

Speaking about his motivations for volunteering as an observer, Antasar Bashir-Suleman who is studying Chemistry commented: “I started volunteering as I wanted to help out 91ֱ�� in getting as many people vaccinated as possible. Whilst volunteering, I met many different people (volunteers, staff and patients) from all scopes of life and I made some friends.”

Hundreds of students have volunteered not just in 91ֱ��, but also across the world including as far afield as Saudi Arabia. Incredible students from The University of Manchester have demonstrated that no matter where you are, we can all make a real impact as part of a community.

Volunteers can still get involved with the vaccination efforts by signing up on the University's .

• Watch our

In addition to the deaths from COVID-19, longstanding socioeconomic and geographical health inequalities for a range of other conditions also worsened during the pandemic, say the research team from the Universities of Manchester and York.

More people were estimated to have died from all-causes in deprived areas across all age-groups, but the differences between deprived and affluent areas were greatest amongst younger people.

For all-cause mortality in the most deprived areas, 15 to 44 year olds were estimated to have had 480 excess deaths, compared to 42 in the most affluent, or over 11 times as many.

And 45 to 64 year olds were estimated to have had 3,150 excess deaths in the most deprived areas , compared to 1,050 in the most affluent, or 3 times as many.

By comparison, estimated excess deaths for those aged 75 to 84 were 5,916 in the most deprived areas and 4,279 in the most affluent, or 40% higher; for those aged 85 or over they were 5,771 in the most deprived and a similar level of 6,094 in the most affluent.

For mortality caused by COVID-19 and respiratory illness, in the most deprived areas, 15 to 44 year olds were estimated to have had 268 excess deaths, compared to 51 in the most affluent, over 5 times as many.

Similarly, 45 to 64 year olds were estimated to have had 2008 excess deaths in the most deprived areas , compared to 681 in the most affluent, or 3 times as many.

By comparison, estimated excess deaths for those aged 75 to 84 were 5069 in the most deprived and 3655 in the most affluent, or 40% higher.

For those aged 85 or over they were 5,302 in the most deprived and a similar 5,636 in the most affluent.

To a degree, the differences were lessened when age structure within deprivation strata was taken into account as younger people live in more deprived areas. However, they remained significant.

The research team used ‘Years of Life Lost’ (YLL) as an alternative measure of premature mortality, measuring the ‘excess’ years lost during the pandemic compared with previous years.

The measure accounts for both the number of deaths and the age at which those deaths occurred and allows comparison between causes of death and across population groups

YLL adjusts for baselined levels across strata of interest such as different life expectancies for men and women.

There were an estimated 763,550 excess YLL in England and Wales in 2020 compared to 2019, 85% of which were directly attributed to COVID-19 or another respiratory disease.

Excess YLL varied widely across the regions, with per capita rates in the North West over three times as high as those in the South West of England

Rates also varied across social groups: the most deprived fifth of areas were 1.8 times those than in the least deprived fifth.

For every death, an average of 9.1 years of life were lost in the least deprived fifth of areas, compared to 10.8 years in the most deprived fifth. For COVID-19/respiratory deaths the numbers were 8.9 and 11.2 years, respectively.

More years of life were lost for men on average, 10.5 in COVID/respiratory deaths and 10.8 in all-cause deaths, compared to 9.5 and 8.2 for females, respectively.

The pandemic exacerbated longstanding socioeconomic inequalities, with the ratio of observed years of life lost for the most deprived fifth of areas compared to the most affluent increasing from 1.56 in 2019 to 1.64 in 2020.

Professor Evan Kontopantelis from The University of Manchester said: “The pandemic widened pre-existing health inequalities across England and Wales: regions and social groups with the highest baseline mortality rates experienced the greatest impact on years of life lost.

“Linked to this, we think the impact of the pandemic may have been higher than previously thought on the most deprived areas of England and Wales, with more younger people dying directly or indirectly from COVID-19 in these areas.”

Professor Tim Doran from the University of York said: “Our findings support the notion that Years of Life Lost can be more informative for determining unmet needs and informing policy for this or future pandemics.

“In particular, it could provide vital information to aid the targeting of vaccines, financial aid and social support during this and future pandemics.”

This paper is not yet peer reviewed, the authors felt its contents were sufficiently in the public interest to disseminate to the public

The paper Excess years of life lost to COVID-19 and other causes of death by sex, neighbourhood deprivation and region in England & Wales during 2020 is available via the

According to the research team, deaths compared with those expected from historical trends were unequally distributed, both geographically and socioeconomically.

The highest excess mortality rates in England and Wales were in the West Midlands, the North East, and the North West. The lowest rates were in the South West of England and Wales.

There were 62,321 excess deaths in England and Wales in the first 30 weeks of the pandemic. Of these, 46,221 were attributable to respiratory causes, including COVID-19, and 16,100 to other causes.

Only 78 excess deaths per 100,000 people occurred in the South West of England and in Wales; 130 per 100,000 occurred in the West Midlands.

And 93 excess deaths per 100,000 people occurred in the most affluent fifth of areas, whereas there were 124 per 100,000 in the most deprived.

Other findings included:

• There were 6,887 excess cardiovascular & diabetes, and 1,668 excess cancer deaths over the study period.
• There were fewer than expected cancer deaths in hospitals (-6,655), hospices (-2,186), and care homes (-917), but more in private homes (10,665).
• The overall excess mortality rate for England and Wales directly attributed to COVID-19 infection or respiratory causes was 77 per 100,000 population

Professor Evan Kontopantelis, a data scientist from The University of Manchester led the study. He said: “Our analysis provides a comprehensive picture of excess deaths during the first 30 weeks of pandemic, including major causes both related and unrelated to COVID-19 infection.

“The models demonstrate that the COVID-19 pandemic has caused many more deaths than would have been expected during the same time-period.

“But for England and Wales, these deaths were not evenly distributed across the population, with rates varying markedly by region, and between deprived and less deprived neighbourhoods.”

The analysis was carried out using Office of National Statistics weekly mortality data from December 2014 to October 2020 for England and Wales.

In England and Wales, a fifth of excess deaths during the first wave of the pandemic - from 7 March to 8 May 2020 - were attributable to causes other than COVID-19.

Delayed responses to acute health conditions and exacerbations of pre-existing health conditions led to substantial increases in mortality for cardiovascular disease, diabetes and other conditions.

However, mortality rates for some health conditions, including other infectious respiratory diseases, fell.

The researchers say the variation in rates reflects population susceptibility, in terms of age and pre-existing disease as well as local factors such as housing density, transport infrastructure and air quality.

But a population’s occupational mix and ability and willingness to engage in public health measures such as social distancing and the capacity and quality of local public health, social and healthcare services could also play a part.

Professor Doran, from the Department of Health Sciences at the University of York and senior author of the study, added: “These results emphasise that regional and socioeconomic variations are relevant to decisions about future pandemic planning, including current and future phases of vaccination roll-out.

“Immediate and longer-term recovery planning for communities and their health and social services should reflect historical disparities as well as the COVID-19 related patterns described in this study.”

The paper Excess deaths from COVID-19 and other causes by region, neighbourhood deprivation level and place of death during the first 30 weeks of the pandemic in England and Wales: a retrospective registry study is published in Lancet Regional Health-Europe

New research published today, in , describes a new family of enzymes (ligases) which can assemble the key chemical building blocks required for pharmaceutical production. The newly discovered enzymes can effectively enable different molecules to be stuck together by creating what is known as amide bonds. This discovery paves the way to more efficient and sustainable production of pharmaceuticals and other valuable chemicals.

The new findings have demonstrated that the ligase enzymes can accept many substrates, but in some cases proved too unstable for practical use. To overcome this problem, the researchers mutated the enzymes to create more robust and stable variants which were shown to have important practical applications and could be used to make pharmaceuticals. They were able to make key amide containing precursors of various antiviral agents, including a drug from Pfizer that is currently in clinical trials for the treatment of COVID-19. They also made the key amide component of an anticancer agent in clinical trials for leukaemia. Finally, they showed how the ligases could be used to generate derivatives of ibuprofen which are being developed as potentially improved anti-inflammatory agents.

Amide bonds are very important in nature. For example, the protein molecules that control the functions of all living organisms are held together by amide bonds, which form a link between the carbon and nitrogen atoms of amino acid building blocks.

The amide bond can also be used to construct a raft of synthetic, non-natural, molecules including many of the most important pharmaceuticals that we rely on today and agrochemicals that can boost crop yields to feed the growing population. In addition, the amide bond is also very strong and is used to construct hard wearing materials (polyamides) including, textiles and carpets.

Prof Jason Micklefield who led the 91ֱ�� team said: “We are confident that our ligase enzymes offer many advantages over the existing methods used to make amides. We are also optimistic that our enzymes can find real word applications in the manufacture of new medicines and other useful products.”

“The ligase enzymes provide a cleaner more efficient and rapid way to construct amide bonds. This could enable pharmaceuticals to be produced in fewer steps, with less waste and at lower costs than the typical chemical processes used today.”

For many years, scientists have sought to develop new synthetic methods to construct amide bonds. To date most of these methods have relied on toxic chemical reagents and dangerous volatile organic solvents which are damaging to the environment. Most of the existing methods also lack selectivity and result in by-products. Consequently, amide containing molecules, including pharmaceuticals, often require multi-step manufacturing processes which make these products expensive.

The team in 91ֱ��, went searching for natural catalysts (enzymes) that could construct amide bonds in a cleaner, more efficient and sustainable manner using water as a solvent. They investigated pathways used in bacteria to produce amide containing molecules (natural products). They found a family of ligase enzymes that bacteria use to make amide containing toxins that kill plants.

Initially the team explored the use of these ligases to make herbicides, which might be deployed in farming to improve crop yields. However, when they used X-ray crystallography to determine the structure of one of the ligase enzymes, they realised that the enzyme active site was relatively open and could accommodate a much wider range of substrate building blocks for production of pharmaceuticals.

The research, ‘Impact of COVID-19 on diagnoses, monitoring and mortality in people with Type 2 diabetes in the UK’ was published in The Lancet Diabetes Endocrinology today. It was funded by the National Institute for Health Research Greater 91ֱ�� Patient Safety Translational Research Centre (NIHR GM PSTRC) which is a partnership between The University of Manchester and Salford Royal hospital.

In April 2020 alone, according to researchers, there was a drop of 70% in recorded diagnoses of the condition compared to expected rates based on 10-year trends in 23 million people. Also, in April, rates of diabetes monitoring (HbA1c blood tests), in people with type 2 diabetes, was reduced by 77% in England, with an 84% reduction across Northern Ireland, Scotland and Wales.

Dr Matthew Carr from The University of Manchester, and lead for this study at the GM PSTRC, said: “Outcomes significantly improve for patients when type 2 diabetes is diagnosed early and regularly monitored. When the condition goes unchecked complications can develop which can be more complex to treat. Prior to the pandemic, diagnosis and monitoring relied upon face-to-face contact so it is no surprise to see an initial reduction, as it just wasn’t possible for patients to receive the necessary level of monitoring. However, to see such a significant drop over the course of 9 months is concerning and is an indication of the challenges faced by healthcare services during the pandemic.”

The research also revealed a significant reduction in the prescribing of the two drugs commonly used to manage the condition, insulin and metformin. The rates of diagnosing and monitoring were particularly evident in older people, in men and in those from deprived areas.

Dr Carr continued: “Importantly, our research has identified the scale of the problem, along with information on population characteristics. This will help healthcare services to address the backlog of diagnosing, testing and prescribing. Effective communications should ensure that people living with diabetes remain engaged with diabetes services. There also needs to be a greater emphasis on providing relevant information and, when appropriate, glucose monitoring systems with easy data uploads to enable remote support.”

The research looked at mortality rates for people with type 2 diabetes during April 2020 and reported a 110% increase in England. Mortality rate increases were less elevated in Northern Ireland, Scotland and Wales (increase 66%).

Professor Martin K Rutter, from The University of Manchester, 91ֱ�� University NHS Foundation Trust, and co-author of the research, said: “In recent years there has been excellent progress made in the management of type 2 diabetes. Resources have been put into early detection and management such that the development of the condition can be delayed and, in some cases, it can be reversed through weight loss interventions. As we recover from the pandemic, our research will help UK healthcare services to focus their efforts on identifying these missed cases and providing more support for people living with diabetes so that they can continue to benefit from these recent advances.”

Nikki Joule, Policy Manager at Diabetes UK, said: "It's incredibly concerning that rates of type 2 diabetes diagnoses in the UK were much lower than previous years during the first part of the COVID-19 pandemic. While figures showed a gradual increase in diagnoses from May to December 2020, they remained well below expected levels.

"These results point towards reduced engagement with healthcare during the pandemic, and highlight the urgent need to ensure that those previously identified by their GP as being at high risk of developing type 2 diabetes receive their annual review. Doing so will ensure that - as appropriate - individuals will receive either a diagnosis, or a referral to the NHS England National Type 2 Diabetes Prevention Programme, or its equivalent.

"Early diagnosis of type 2 diabetes is vital in reducing the risk of serious diabetes-related complications such as problems with the heart, kidneys and eyes. To find out your risk of type 2 diabetes, visit Diabetes UK's Know Your Risk Tool - and if you're concerned that you might be at an increased risk, it's important to speak to your GP."

Type 2 diabetes accounts for around 90% of all diabetes diagnoses and is often linked to being overweight or inactive, or having a family history of the condition. It causes sugar levels in the blood to increase which leads to excessive thirst, weight loss and tiredness. Diabetes, especially when poorly managed, can cause serious long-term problems with the eyes, heart, kidneys and nerves.

Those living in the most deprived neighbourhoods along with ethnic minority groups were the most affected say the team based at The University of Manchester, King’s College London, Cambridge, Swansea and City University.

However, two thirds of adults were in groups whose mental health was largely unaffected by the pandemic finds the study published in The Lancet Psychiatry.

The team analysed monthly surveys between April and October 2020 on 19,763 adults to identify typical patterns of change in mental health, revealing five distinct groups.

The unaffected groups were more likely to be older, white, and from the least deprived areas, with men being especially likely to have consistently very good mental health. According to the research:

• 12% of the sample were in a group that experienced initial declines in their mental health at the beginning of the pandemic then recovered over the summer. Women and parents of school-aged children were particularly likely to be in this group, experiencing significant improvements in mental health around the time schools’ reopened.
• 7% of the sample experienced a sustained decline in their mental health.
• 4% of the sample had mental health that was consistently very poor throughout.

The groups experiencing a sustained decline or consistently very poor mental health were more likely to have had pre-existing mental or physical conditions. They were also more likely to be Asian, Black or mixed ethnicities, and live in the most deprived areas.

The researchers also found that infection with COVID-19, local lockdown, and financial difficulties all predicted a subsequent deterioration in mental health.

The research team analysed the UK Household Longitudinal 91ֱ�� from the University of Essex and the Economic and Social Research Council.

Dr Matthias Pierce, is lead author and research fellow from the Centre for Women’s Mental Health at The University of Manchester.

He said: “It’s clear from this study that in terms of mental health, the pandemic has had a disproportionate impact on minority ethnic groups, those living in deprived areas, others experiencing financial difficulties and those who already had poorer mental health.

“But also we find a large proportion of the population has remained resilient to the effects of the pandemic.”

He added: “The data we used are superior to other surveys because the UK Household Longitudinal 91ֱ�� uses a high quality representative random sample and includes groups such as the digitally excluded who might not otherwise participate.

“Other surveys, especially those which use social media, are often unrepresentative and can lead to unreliable results.”

Senior author, Professor Kathryn Abel from The University of Manchester said: “We are increasingly aware that social and economic advantages have an important influence on how well people are able to cope with challenges that appear to have affected everyone equally.

“The health and social inequalities we already know about for women and for people in poverty relate to different burdens of stressful life events and different resources to deal with them.

“These remain relevant and are important reasons for the differences we are seeing in the mental health trajectories across the pandemic.

Sher added: “For people in ethnic minorities, their experience of the pandemic has meant dealing with both existing discrimination and inequalities alongside higher risks of severe illness, disability and, of course, death.

“This represents a devastating landscape for their mental health borne out in our findings.

“We must respond by making sure services are aware of these disparities and that their offerings are culturally sensitive and appropriate for the complexity of unmet need.”

Using data from UK Biobank - the world’s largest biomedical database - shift work increased the likelihood of testing positive for COVID-19 in hospitalised patients 2-3 fold, depending on the nature of shift work. The effect persisted even after controlling for known COVID-19 risk factors.

The study involved researchers at The University of Manchester, Radcliffe Department of Medicine at The University of Oxford and the University of West Indies.

Supported by the NIHR 91ֱ�� Biomedical Research Centre, Medical Research Council and Wellcome Trust, it is published in the journal Thorax.

Though there are several known risk factors for COVID-19, they do not always explain why COVID-19 outbreaks happen in factories or healthcare settings which is why the investigators investigated the role of shift work.

Shift work was defined in this study as working outside the hours of 9am to 5pm and it is estimated that around a quarter of the UK workforce do some kind of shift work.

The type of shift work or type of occupation, such as health workers, factory workers, didn’t seem to affect the association as occupational exposure to COVID-19 was controlled for in two different ways.

Over half a million people were enrolled in the UK Biobank. Of these 6,442 were tested for COVID-19 in hospital resulting in 498 positive tests between March and August 2020.

In those that had positive tests, 316 did not work shifts, 98 worked irregular shifts and 84 worked permanent shifts, totalling 182. The shift workers were 2.5 to 3 times more likely to be positive with COVID-19 than non-shift workers in those that were hospitalised.

The team also conducted analysis on a subset of biobank participants where the occupational shift work status was updated in 2017.

In the subset, 43,878 participants were used to analyse the effect of shift work with 72 participants being hospitalised for COVID-19. From this analysis shift workers were an even greater 4.5 times more likely to be positive for Covid-19.

The study was led by Dr John Blaikley, a MRC clinician scientist at The University of Manchester and Dr Hannah Durrington also at The University of Manchester. Both authors are Respiratory doctors at Wythenshawe Hospital.

Dr Blaikley said: “This study shows quite a strong association between shift working and being hospitalised for Covid-19, even after controlling for existing COVID-19 risk factors.”

Dr Durrington said: “It is of paramount importance that the health and working conditions for shift workers are improved.”

Dr Blaikley added: “The UK Biobank does not fully reflect the diversity of the UK, therefore further studies especially in ethnic minority populations are needed.

“It’s hard to explain the exact cause of this association though we think workplaces should be made aware of these risks so they can take appropriate precautions for their staff.

“And we do believe it should be possible to substantially mitigate these risks through good handwashing, use of face protection, appropriate spacing and vaccination”, concluded Dr Durrington.

The paper ‘Shift work is associated with positive COVID-19 status in hospitalised patients’ is published in Thorax and an embargoed copy is available 

Many people recovering from COVID-19 suffer from long-term symptoms of lung damage, including breathlessness, coughing, fatigue and limited ability to exercise.

COVID-19 can lead to inflammation in the lungs due to the infection and the immune system’s reaction to it. The inflammation may improve over time, but in some people it persists.

In severe cases, the lungs may become scarred. The scarring causes stiffness in the lungs, which can make it difficult to breathe and get oxygen to the bloodstream, resulting in long-term breathlessness and difficulty managing daily tasks.

This inflammation and scarring of the lungs is called ‘interstitial lung disease’.

Now, this study, called the UK Interstitial Lung Disease Long-COVID19 (UKILD-Long COVID) study, will investigate whether post-COVID-19 lung damage will improve or worsen over time, how long it will last, and the best strategies for developing treatments.

Early evidence indicates that lung damage occurs in approximately 20% of patients discharged from hospital, but the effects on people who experience long-Covid in the community are currently unclear.

Matthew Gordon, 44, from Bristol, who was hospitalised with COVID-19 in January 2020, said of his experience: “Nearly two months on, I’m slowly recovering. The coughing has stopped, which is the greatest relief, and it’s no longer a struggle to breathe. However, my muscle strength is still very weak and doing mild exercise such as jogging, or even walking while talking, can make me short of breath. My latest review with the respiratory consultant a couple of weeks ago found there was still some slight crackling on my lungs and my lung capacity was reduced but had improved since January.

“During my time in hospital I took part in trials, such as REMAP-CAP treatment trial, and now I’m keen to take part in research to learn more about the long-term effects of COVID on the lungs of people like me and how we’re recovering.”

This study, led by researchers at Imperial College London, will bring together researchers and clinicians from 15 research centres** and will include patients already in COVID-19 studies, such as the study.

Professor Gisli Jenkins, at Imperial College London, who is leading the study, said: “This is an ambitious study that will help us understand how common and severe the long-term pulmonary consequences of COVID-19 are, and will help us develop new treatment approaches for people suffering from long-term lung inflammation as a result of COVID-19.”

“Breathlessness is a big problem for many people with long-COVID, particularly on exertion. For people with more severe lung scarring, this can be a devastating disease. We don’t yet know how frequent and how long-term the consequences will be. Even if the long-term outcomes are no worse than for people with similar lung damage from flu, the sheer numbers of people who have had COVID-19 are so huge.”

Dr Karen Piper Hanley, at the University of Manchester, who will study the cells in the lungs, said: “This MRC award pulls together our best researchers and clinicians around the UK to build our understanding of COVID-19 and long-term lung damage post infection, which for some individuals can be devastating. By bringing together this collective knowledge and expertise, this project has the potential to impact patient care globally and develop new treatments to improve lung damage post-COVID-19.”

The study is funded as part of UKRI’s COVID-19 Agile Call, which has so far invested more than £180 million in over 450 projects and consortia to address the impacts of the COVID-19 pandemic.

Science Minister Amanda Solloway said: “It is thanks to the pioneering work of our brilliant scientists and researchers that we now know so much more about COVID-19 than we did just one year ago – including the lasting effects it can have on patients.

“Bringing together some of the UK’s finest researchers, this new nationwide study will analyse the full impact of lung damage caused by the disease, helping to inform new treatments that could benefit patients across the world, as we build back better from the pandemic.”

Professor Fiona Watt, Executive Chair of the Medical Research Council, part of UKRI which funded the study, said: “This research is key to understanding how and why the virus causes some people to suffer long-term lung effects after COVID-19 infection. It will be an important tool in developing more effective treatments for patients.”

To understand the full spectrum of lung impacts, the study will include a range from patients, from those who have been hospitalised or placed on a ventilator to those in the community who had less severe COVID-19.

They hope to recruit approximately 250 people with symptoms suggestive of possible lung scarring, such as breathlessness or a persistent cough, to find out more about their long-term lung damage at three and 12 months after COVID-19 infection.

Cutting-edge xenon MRI scans will be performed in a subset of patients. These use a safe, inert gas which is inhaled, so the scan can measure the effectiveness of gas exchange inside the lungs.

The proof of concept system combines the movement and interaction of staff and patients with genomic sequencing of the virus, helping to signpost how best to improve patient pathways, staff movement and reduce risk.

They identified hotspots within hospitals  where patients and staff had likely been in contact and shared similar or identical variants of the virus SARS-CoV-2- which causes Covid-19.

The data collected between March and June 2020, was the result of a unique collaboration between 91ֱ�� scientists, clinical staff and hospital executives whose results are published in the journal Elife.

The work, which took place across five hospitals in North West England, could have an important impact on infection control. The team applied genome sequencing to throat and nasal swabs obtained from 173 healthcare workers and patients.

Viruses, like all organisms, accumulate small genetic changes through time which are usually completely neutral and don’t give the virus any additional advantages.

The 91ֱ�� team took advantage of the natural genetic changes in the virus to understand how closely related samples from different staff and patients affected by the virus were.

If the COVID-19 genome from one affected individual appears almost identical to that of another, this shows they share a common, nearby source of infection.

Combining this information with data on patient and staff movement can identify where and when clusters of infection occur.

While COVID-19 variants are identified using genomic sequencing in a process that can take at least a week to complete, the team are confident the process can now be carried out as quickly as 48 hours. The approach is therefore in a position to be scaled up at pace.

Dr Jamie Ellingford from The University of Manchester said: “The methods applied in this study to completely characterise what the virus looks like in each sample goes above and beyond routine testing strategies.

“And that can enable identification of areas of hospitals where outbreaks are occurring and help alert infection control teams.”

A potential limitation to the approach is that at any given time point, two individuals can share a similar variant by chance, rather than as a result of interrelated infections.

To overcome that, the team sequenced the virus in people collected from the Emergency Department and across over 30 hospital sites.

Using data from this wider group collected at a similar time point, they could identify clusters of individuals who shared viruses more genetically similar than would be expected by chance.

Dr Ellingford said: “It is extremely important to understand the effectiveness of infection control methods if we are to reduce and prevent SARS-CoV-2 transmission in hospital.

“While vaccines may reduce risk to individuals in hospital, the risk of infection will still exist and infection control is strongly needed to ensure patient and staff safety.

“We think, however, an important tool in the infection control armoury is viral genome sequencing, which offers a realistic possibility to track and identify root-causes of hospital-acquired transmissions.

“It is able to alert us to individuals who have been in contact during a given period and share genetically similar viral samples.

“And that can lead to targeted interventions and ultimately prevent avoidable harm to vulnerable individuals who acquire COVID-19 in hospital.”

Graeme Black is Professor of Genetics and Ophthalmology at the University of Manchester. 

He said “Once hospitals have identified clusters there are a range of measures they can take to make them safe.

“With this information hospital managers can, for example, evaluate existing infection control practices and easily check which ones are working most effectively. The use of PPE could also be adapted according to where a cluster might be.

“But we also suggest these data support the widespread adoption of screening strategies for healthcare workers who may be presymptomatic or asymptomatic shedders of SARS-CoV-2 who are important contributors to SARSCoV-2 outbreaks.

“We also think that developing methods to more accurately track movement could be useful in hospital to extend the characterisation of contacts between individuals and to understand the accuracy of the assumptions enforced in this study.”

In the by University of Manchester academics, most of the respondents reported adhering to the rules, with just 5% or fewer people reporting active resistance to Government restrictions.

However, the survey, carried out in April 2020 and published in BMC Public Health, revealed that better adherence was associated with older age, being a woman and having a white ethnic background.

People from ethnic minority groups were 5.9% less likely to adhere than people who identified as white; women were 6.3% more likely than men.

The findings reflect the higher mortality rates associated with COVID-19 among men and people from BME communities than in the broader population.

The study also found that adherence is likely to be increased or sustained by enhancing people’s capabilities, providing them with sufficient opportunities and ensuring they are appropriately motivated.

It was funded by the University’s 91ֱ�� Centre for Health Psychology and supported by the NIHR 91ֱ�� Biomedical Research Centre and NIHR Greater 91ֱ�� Patient Safety Translational Research Centre.

Lead author Professor Christopher Armitage said: “Some of these COVID-19-related measures are likely to remain in place for years, so it is important that adherence to some form of restriction is sustained.

“This study shows that certain groups are less likely to adhere to the Government’s COVID-19-related instructions.

“As these groups show a higher mortality from COVID-19, it is critical that we develop strategies to address this.

“According to our findings, part of the answer will involve interventions targeted at people with black, Asian and minority ethnic backgrounds, men and younger people.

Professor Armitage, who also leads the Greater 91ֱ�� Patient Safety Translational Research Centre Behavioural Science sub theme added: “Sustaining people’s capabilities, opportunities and motivations will be a key way to achieve this.

“Interventions that help people to establish new habits and to regulate their emotions may be particularly effective at increasing and sustaining people’s adherence.”

A  copy of the paper: Identifying Targets For Interventions To Support Public Adherence To Government Instructions To Reduce Transmission Of SARS-CoV-2 can be downloaded

A UK wide survey of 2252 adults, carried out five weeks into the first lockdown revealed 95% of those surveyed were following lockdown restrictions. Of that 95% more than 80% reported finding it challenging. Adjusting to changes in daily routines, and mental and physical health struggles were the most common challenges faced by participants. Women and adults under the age of 55 were most likely to report experiencing challenges.

The research, ‘What challenges do UK adults face when adhering to COVID-19-related instructions? Cross-sectional survey in a representative sample’*, was published in the journal, Preventive Medicine. It was conducted by researchers at The 91ֱ�� Centre for Health Psychology and the National Institute for Health Research Greater 91ֱ�� Patient Safety Translational Research Centre (NIHR GM PSTRC). The Centre is a partnership between The University of Manchester and Salford Royal NHS Foundation Trust. .

Dr Chris Keyworth, research fellow in the Behavioural Science sub theme at the GM PSTRC and lead for this study, said: “Our research shows that during the first UK lockdown a high proportion of the people we surveyed did stick to the government rules. Understanding the impact of this on mental health is vital when looking at how to encourage people to do this long term and into the future.

“The first step is to identify the biggest challenges people faced and for which age group and gender.”

The challenge the most people reported facing was the changes in daily routines, followed by the impact on mental health and then the issues around physical health.

Dr Keyworth continued: “According to our survey more than 40% of people said they struggled with their mental health during the first lockdown. This is interesting because, in comparison, according to a 2016 study, one in six people reported experiencing a common mental health problem in a given week in England. This goes some way in quantifying the profound affect the restrictions had on the population at the time.”

The research highlights the importance of tailoring public health messages to age groups, genders or those with certain characteristics. The study’s findings suggest an urgent need to prioritise interventions which address the physical, psychological and social impacts of the pandemic. These may include interventions that aim to help people to change habits and support them in establishing new routines when faced with the sudden introduction of strict rules such as lockdown. Greater investment in services to improve physical and mental health that can be delivered remotely should also be a priority. Home-based interventions to promote physical health should be developed and more work put into improving access to healthcare professionals remotely.

These interventions should then be targeted at women, those under 55 and people without care commitments as they were identified as the most likely to struggle during a full lockdown.

Professor Chris Armitage, lead of the GM PSTRC’s Behavioural Science sub theme, said: “The findings show that by-and-large, the British public have been adhering to government COVID-19 instructions, but following the government lockdown rules comes at a personal cost. Greater attention needs to be paid to how following the rules can be sustained with targeted support measures.”

Dr Keyworth concluded: “Lockdown is undoubtedly challenging and, to ensure any future government restrictions and guidelines are followed it is important to learn from the behaviour of the population at a time when a high number of people were following the rules. We hope that our research will help to improve patient safety by aiding understanding. It can be used to guide the design of interventions and inform public health messaging both now and into the future.”

The Alderley Park Lighthouse Lab is one of several government super-labs across the UK, which forms the Lighthouse Lab network: the largest diagnostics network in UK history. At the end of October, the network had the combined capacity to process half a million tests samples each day.

The Medicines Discovery Catapult at Alderley Park co-ordinated the build of the national Lighthouse network following a request from the Department for Health to rapidly expand Covid-19 testing, and runs the Cheshire Lighthouse Lab.

The Alderley ‘super-lab’, required an army of scientifically-trained volunteers to help increase the UK’s COVID-19 testing capacity when the site was created from scratch in March.

Dozens of University of Manchester staff and postgraduate research students across the campus offered up their expertise and services.

Nearly a year on, the lab has processed its 7 millionth sample, and following the call for volunteers, has subsequently provided year in industry placements for 14 undergraduate students from the University.

Mark Wigglesworth, Site Director at the Alderley Park Lighthouse Lab, paid tribute to the scientists who helped make the Alderley Park facility a reality.

Mark said: “We were astounded by the sheer number of volunteers who stepped forward at the start of the year to dedicate their time and energy towards a common goal; how the application of technology and science can contribute towards the eradication of the terrible pandemic we’ve all had to endure this year.

“Over 1,000 individuals from all walks of life answered the call and within a few short weeks, we were operational. Following the launch, we’ve had a great deal of these volunteers join the team as full-time staff.

“Today, our almost 600 staff members can sample up to 50,000 tests a day, and we’ve just processed our 7 millionth sample. It’s a tremendous figure, but one that would have been impossible were it not for the tenacity and hard working ethos of our volunteers and wider team.”

Several University of Manchester placement students, including Iona Glidden, Joseph Turner and Anjali Sivaram, recently gave a presentation about their experiences working with the Alderley Park team throughout the pandemic.

Iona commented: “We received a lot of virtual applause from the staff members at the University of Manchester, who found the talk very interesting and informative.”

Anjali said: “They were very proud of all their students who are contributing to the national effort against Covid”. And when asked about how they found the work at the Lighthouse, Joe concluded: “it is a privilege to be on the frontline for one the most difficult time periods of our generation.”

The Phase 3 study is testing the safety and effectiveness of a new two-dose vaccine regimen, versus a placebo, in preventing moderate to severe/critical coronavirus disease.

The vaccine candidate has been developed by , as researchers around the world continue to work to secure a range of vaccines and treatments to help tackle coronavirus.

Dr Tim Felton, an Honorary Consultant at MFT’s Wythenshawe Hospital, is the Trust’s Clinical Lead for all COVID-19 research, as well as the Principal Investigator at MFT for the Janssen Phase 3 study.

Dr Felton, who is also a Senior Lecturer at The University of Manchester and a researcher within Respiratory Theme, said: “Throughout all the research we have undertaken into COVID-19 at MFT, finding a safe and effective vaccine has been the top priority.

“Recruiting our final participant into this study is a major step forward in our fight against coronavirus – and I’d like to thank every person who has volunteered to take part in this vital research.

“It is critical that we explore a range of vaccination options to give us the greatest chance of protecting as many people as possible, as we continue to the global effort to tackle the COVID-19 pandemic.”

Dr Claire Cole, the Head of Research Delivery at MFT, was the .

MFT has now recruited 405 participants to the study, exceeding its target of 400 within just eight weeks. Globally, recruitment into the study is due to complete in March 2021, with 6,000 volunteers taking part in the UK and 30,000 worldwide.

Dr Cole said: “Although I have worked in health research for a number of years, I never cease to be amazed by the life-changing – and sometimes lifesaving – impact research can have.

“I wholeheartedly believe in the importance of taking part in research and was honoured to be the first person in the world to be recruited to the study, as part of this vitally important COVID-19 vaccine trial.

“But I am especially proud of the resilience of the multidisciplinary study team here at MFT, who have managed to recruit the required number of participants and start administering second doses within just two months – an incredible achievement considering the current global landscape.”

Across the UK, volunteers from a variety of age groups and backgrounds – including some of the thousands who registered to be contacted about vaccine studies through the – have been taking part in the study.

Stephanie Gill, a headteacher, was contacted to take part in the study at MFT after signing up to the vaccine registry.

The 51-year-old from Sale, 91ֱ��, said: “When I received my invite to take part, I was really excited.

“I’ve never taken part in research before, but all the research staff here have been absolutely brilliant.”

Having now received two doses as part of the blind study, Stephanie does not know whether she received the vaccine candidate or the placebo.

“While I of course hope I received the vaccine, the blind element is the whole point of the trial. I just wanted to contribute, so even if I’ve had the placebo, I’ve contributed to this important research.”

All study participants will be monitored for 112 weeks after vaccination.

At MFT the trial is being delivered in collaboration with the

More about the Janssen (Ad26.COV2.S) vaccine

Like other vaccines, Ad26.COV2.S is expected to prepare the body to defend itself against infection. It contains genetic instructions for what is known as ‘the spike protein’, which is present on the surface of the coronavirus.

When a person is given the vaccine, their cells will read the genetic instructions and produce the spike protein. The person’s immune system will then treat this protein as foreign and produce natural defences – antibodies and T-cells – against it.

If the vaccinated person later comes into contact with COVID-19, their immune system will recognise the virus, with antibodies and immune cells working together to kill it and prevent its entry into the body’s cells.

• The UK public can support the national effort to speed up vaccine research and receive more information about volunteering for clinical studies by visiting:

• The ENSEMBLE 2 Janssen study is trialling a two-dose Janssen COVID-19 vaccine regimen. The results of a separate study, ENSEMLBE, which trialled a single-dose Janssen COVID-19 vaccine candidate, .

Picture: Dr Claire Cole – Head of Research Delivery at MFT –who was the first global recruit to the trial. The photo has taken in November when she had her first dose.