HERC and COVID-19
Despite the practical challenges we are all facing, several members of the HERC team have been able to use their skills and experience to contribute to the scientific evidence base on COVID-19.
talks & MEDIa
Oxford BRC Virtual Symposium on Tackling COVID-19 together: Building a multi-disciplinary approach to help vaccinate the world. On the 8 September 2021, HERC hosted a virtual symposium to provide a multi-disciplinary forum focusing on effective ways to promote vaccine uptake and to ensure public support for the effort and resources required to vaccinate the world. The symposium brought together perspectives of immunologists, epidemiologists, psychologists, economists and political scientists.
Much of the intense COVID-19 research effort worldwide has been undertaken within traditional academic disciplines. Yet tackling COVID-19 effectively, and dealing with its long-term health and economic impacts, will require a multidisciplinary research effort. See links below for recordings of some highlights from the symposium, where our speakers present the latest evidence and discuss the challenges and opportunities ahead.
Professor Mark Jit (Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine) What will be required to achieve herd immunity in the UK and Globally?
Associate Professor Mara Violato (Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford) COVID-19’s hidden cost: Evidence from the CANDOUR study on global mental health:
Professor Sir Andrew Pollard (Director of the Oxford Vaccine Group, University of Oxford) The challenges ahead for the UK and globally
Professor Daniel Freeman (Department of Psychiatry, University of Oxford)
Overcoming vaccine hesitancy: Evidence from OCEANS studies
Professor Raymond Duch (Director of Centre for Experimental Social Sciences, Nuffield College, University of Oxford): Do vaccine lotteries or payments work best? Evidence from the CANDOUR study
Professor Mitesh Patel (Perelman Center for Advanced Medicine, University of Pennsylvania, USA) A megastudy of text-based nudges encouraging patients to get vaccinated at an upcoming doctor’s appointment
Susan Brown (Public Policy Engagement at GAVI, the Vaccine Alliance) Covid-19: Beyond the science.
Dr Koen Pouwels (Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford) How long do vaccines confer immunity?
Dr Laurence Roope (Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford) Global public opinion on vaccine donations, mandates and pandemic preparedness: Evidence from the CANDOUR study
Monday 25 January 2021: Dr Laurence Roope was interviewed by Tim Harford, as a guest on Radio 4's "How to Vaccinate the World" Podcast available here. Dr Roope discussed COVID vaccine prioritisation issues which have been explored in the CANDOUR study, an Oxford University project, involving global collaborators, which is led by Professor Philip Clarke.
For further project information, please see the Candour Study site.
Professor Philip Clarke, Director of HERC, was interviewed on the BBC Radio 4 Today programme, on 18 November 2020 at around 6.45am, speaking about the recent @ConversationEDU article on French & UK approach to COVID-19 vaccine prioritization.
On the 11 November 2020, Professor Charles Manski (Department of Economics and Institute for Policy Research Northwestern University) presented his work on “Forming COVID-19 Policy Under Uncertainty”, based on his recent paper in the Journal of Benefit-Cost Analysis. Professor Manski has given permission for his talk to be featured on our site and we will be publishing this soon.
September 2020: Dr Laurence Roope was interviewed by Biz News, based in South Africa, to discuss who will get the Covid-19 vaccine first and how to plan its roll-out. Larry's interview can be found around 26 minutes into this Podcast.
COVID-19 research ACTIVITY INVOLVING HERC people
Update on HERC COVID-19 research
HERC project team: Koen Pouwels, John Buckell, Laurence Roope, Paolo Candio, Mara Violato and Philip Clarke
Koen Pouwels contributed to several publications and preprints on COVID-19, including articles published in the New England Journal of Medicine and various journals from the Nature family. The publication focused on antibody responses to natural SARS-CoV-2 infection, the impact of prior infection on antibody trajectories after a single COVID-19 vaccination and antibody test-based vaccine prioritisation, the impact of second doses of vaccination on antibodies and associations between antibody levels and protection against infection, monitoring of populations at increased risk for infection in the community, improving the usefulness of biased SARS-CoV-2 testing data using a causal debiasing framework, the impact of vaccination on Long Covid symptom trajectories, the effect of vaccination on transmission of the Alpha and Delta variant, the emergence of the Alpha variant in the UK, and changes in symptoms associated with the Omicron variant.
John Buckell and Koen Pouwells also published a paper on changes in risk-compensatory behaviours and contacts upon vaccination.
Meanwhile, Laurence Roope, Paolo Candio, Mara Violato and Philip Clarke published evidence from the CANDOUR study of broad-based support in high-income countries for donating COVID-19 vaccines to low-income countries.
Finally, Liz Morrell and Laurence Roope contributed to a qualitative study on GP’s perceptions of the pandemic's impact on antibiotic prescribing and stewardship in England. Participants reported fewer consultations for respiratory infections early in the pandemic, but a lower threshold for antibiotic prescribing. Subsequently, prescribing returned to more usual levels.
THE CANDOUR (COVID-19 VACCINE PREFERENCE AND OPINION SURVEY) STUDY
An effective vaccine will help end the COVID-19 pandemic. Clinical trials for the COVID-19 vaccine are very promising. While enormous research effort and resources have been put into vaccine development, there is currently no evidence-based framework for the allocation of a vaccine to both maximise outcomes and ensure an equitable distribution. Current trials indicate that a vaccine offering protection against COVID-19 is imminent and will receive regulatory approval very soon. Governments will have to make immediate decisions on how to allocate available supplies. In many countries, these will not be sufficient for universal vaccination, and so choices will need to be made as to which groups are prioritised to receive a vaccine. The CANDOUR project is conducting national representative surveys in twelve countries in anticipation of trial results being finalised in the coming months. It will be used to help develop a fair and efficient allocation mechanism to facilitate vaccine prioritisation. Scholars from HERC: Mara Violato, John Buckell, Laurence Roope, led by Professor Philip Clarke are collaborating with Prof Ray Duch of Nuffield College, Oxford and other project partners in France, Italy, New Delhi, South America and Canada. See the Study website for latest activity.
The Coronavirus Infection Survey
This is one of the largest SARS-COV-2 longitudinal surveys in the world - testing 150,000 participants a fortnight by October - that evaluates questions which are directly relevant for Policy Makers. Throat and nose swabs are taken to be able to assess changes in the prevalence and incidence at the national and local level and how behavioural, health and socio-economic risk-factors for infection change over time.
By measuring levels of antibodies over time within individuals and relating these changes to new infections within those individuals, the study will be able to assess whether and for how long antibodies protect against new infections.
Koen Pouwels has been heavily involved in the design of this study and is performing a large part of the analyses together with Iryna Schlackow. Koen has also co-authored recent papers on i) improving COVID-19 surveillance in long-term care (published in BMC Medicine), ii) 'SARS-CoV-2 antibody waning among healthcare workers (published in Clinical Infectious Diseases), iii) and the protective effect of antibodies against (symptomatic) SARS-CoV-2 infection among healthcare workers (published in New England Journal of Medicine).
Study results are published on a weekly basis via these ONS pages
The study has directly informed several UK policies and is discussed virtually every week in media such as the BBC, Financial Times, and the Guardian. More details can also be found in pre-prints that are currently under peer-review at different stages with various scientific journals:
1) A paper published in Lancet Public Health showing the percentage of individuals in the community testing positive for SARS-CoV-2. The paper uses multilevel regression and poststratification to ensure respresentative estimates of the number of people testing positive for SARS-CoV-2 over time are obtained from the survey and further describes how risk-factors for infection changed substantially over time.
2) A preprint showing that community SARS-CoV-2 infections show marked variation in viral load. The paper suggests that cycle threshold (Ct) values should be reported instead of just whether a person test positive or negative. Declines in mean/median Ct values were apparent throughout August and preceded increases in positivity rates, suggesting that Ct values could be a useful epidemiological early-warning indication.
3) A preprint showing how positive SARS-CoV-2 PCR tests compatible with the new B.1.1.7 variant (also known as Variant of concern or UK variant) were largely underlying the increase in the number of positive tests in December and January. Direct population-representative estimates from the survey show that this new variant leads to higher infection rates compared to other variants, but that there is no evidence that the relative growth of this variant is larger among a particular age, such as children. This research and interviews with Koen Pouwels related to this paper were reported in various media in The Netherlands and Belgium (all in Dutch unfortunately)
Oxford University Hospitals Staff Testing
Data from a longitudinal seroprevalance study of healthcare workers from Oxford University Hospitals. Koen Pouwels contributed to two studies using these data, the first on antibody waning among hospital staff and the second on the protective effect of antibodies against (symptomatic) SARS-CoV-2.
The first paper used Bayesian mixed linear models to investigate antibody waning and associations with age, gender, ethnicity, previous symptoms and PCR results. Serially measured SARS-CoV-2 anti-nucleocapsid IgG titres from 452 seropositive healthcare workers demonstrate levels fall by half in 85 days. From a peak result, detectable antibodies last a mean 137 days. Levels fall faster in younger adults and following asymptomatic infection.
The second paper - which is published in the New England Journal of Medicine - addressed the critical question whether infection with SARS-CoV-2 protects from subsequent reinfection. The study found that prior SARS-CoV-2 infection that generated antibody responses offered protection from reinfection for most people in the six months following infection (adjusted incidence rate ratio, 0.11; 95% confidence interval, 0.03 to 0.44; P=0.002). Further work is required to determine the long-term duration and correlates of post-infection immunity.
RELAXING LOCKDOWN WHILE GENERATING EXPERIMENTAL EVIDENCE
Philip Clarke, Laurence Roope and collaborators proposed a strategy where governments could relax lockdown gradually, in a way that would both provide evidence on whether continued lockdown is needed, and ensure that the risks of infection are minimised and distributed fairly across society. A way to achieve this is alternating lifting restrictions for a limited period (for example, one day) on only half of the population at any one time. Such a policy could be implemented via an odds-and-evens policy based on house number. Government would alternate maintaining and relaxing stay-at-home orders between odd-and-even households. Governments could adapt policy for people without homes or with addresses without numbers. An odds-and-evens policy is one way to lift restrictions gradually and equitably as a controlled trial involving huge numbers of individuals. It would permit the economy to restart and provide a firm evidence-base on which to develop future policy decisions to combat the ongoing epidemic of covid-19.
National Wastewater Epidemiology Surveillance Programme (N-WESP)
N-WESP brings together scientists and collaborators from 23 organisations, including HERC, to investigate the presence and infectivity of SARS-CoV-2 in wastewater. This research will help develop surveillance methods and findings could identify future disease hotspots across the UK. This programme is funded by the Natural Environment Research Council (NERC) as part of the UK Research and Innovation's rapid response to COVID-19.
Koen Pouwels is a co-investigator for the project and will be assessing to what extent the amount of SARS-CoV-2 correlates with the estimated number of people infected in different areas across the country over time. By doing so one can determine the accuracy of a surveillance system incorporating detection of SARS-CoV-2 in wastewater. Given the limited number of tests and low-costs needed for wastewater surveillance this could potentially free up scarce resources. This is especially important given the increase in testing delays that was already observed in several countries even before the second wave.
Group Testing
The challenges presented by testing for SARS-CoV-2 are as much about manufacturing capacity, economics and resource allocation as they are about epidemiology. In this article Koen Pouwels, Laurence Roope, Philip Clarke and collaborators examine the case for whether group (pooled) testing should become a key component of the strategy to combat coronavirus disease 2019 (COVID-19). The study concluded that group testing has the potential to substantially reduce constraints in availability of diagnostic tests for SARS-CoV-2. In many circumstances, it could enable limited numbers of diagnostic tests to be used more efficiently, testing more patients without increasing operational delays. The sensitivity of existing and future tests at different group sizes therefore deserves urgent consideration.
Testing in care homes
Long-term care facilities (LTCFs) are vulnerable to COVID-19 outbreaks. In England it has been estimated that nearly half of COVID-19 deaths occurred in such facilities. Timely epidemiological surveillance is essential for outbreak response, but is complicated by a high proportion of asymptomatic and pre-symptomatic infections and limited testing resources. Koen Pouwels co-authored a paper which is published in BMC Medicine . Koen and his colleagues created a stochastic, individual-based model using detailed information on close-proximity interactions measured by every 30 seconds by sensors worn by all patients all staff in LTCF. The efficacy and resource-efficiency of a range of surveillance strategies, including group testing and testing cascades, which couple (i) testing for multiple indications (symptoms, admission) with ii) random daily testing. Find out what is the best testing approach under different scenarios of resource constraints.
How should a safe and effective COVID-19 vaccine be allocated?
Once a safe and effective COVID-19 vaccine is approved for use by regulators, most countries will not have enough doses for everyone who would ideally be vaccinated. As soon as a vaccine is approved for use by regulators, there will be intense competition for doses, both between and within countries. There are major efforts by international organisations to make a range of potential vaccines available worldwide, with a particular focus on low and middle-income countries.
Alongside these global initiatives, there is increasing recognition of the importance of deciding at a national level how best to allocate the available vaccine - see recent news story: Governments should be thinking of how they would allocate a safe and effective COVID-19 vaccine. In articles published in Pharmacoeconomics – Open and The Conversation, Laurence Roope, John Buckell, Frauke Becker, Paolo Candio, Mara Violato, Philip Clarke and collaborators argue that governments should be thinking about these decisions now, so that allocation can begin immediately after an effective COVID-19 vaccine becomes available.
Designing an optimal vaccination strategy will involve balancing different criteria, such as protecting the most vulnerable; reducing transmission; and allowing life to return to normal. One way of informing how criteria should be weighted is be to seek the preferences of citizens, e.g. via nationally representative surveys. HERC researchers and collaborators are currently engaged in a multi-country survey study seeking public views on how a COVID vaccine should be allocated. This includes eliciting (e.g. through choice experiments) the general population’s ranking of the relative importance of different types of outcomes associated with a COVID-19 vaccination programme – such as health versus economic benefits.
The burden of COVID-19 on children, adolescents and their parents
The disruption caused by COVID-19 to education and work patterns presents an ongoing challenge to both children and their parents. The Co-SPACE study, led by Polly Waite and Cathy Creswell (Departments of Experimental Psychology, and Psychiatry) aims to capture how families are coping during the COVID-19 pandemic, and what parents can do to help support their children’s mental health.
Mara Violato, with the support of the NIHR ARC Oxford and Thames Valley, is conducting health economics research using data from the Co-SPACE study. Mara will investigate the impact of COVID-19 on quality of life of school-age children and adolescents (4-16 years old), as well as on educational (for children) and work-related productivity (for parents) losses as the pandemic unfolds. In addition to providing a timely evidence-base on the burden of COVID-19 on children, adolescents and their families, the findings of the study will be particularly valuable as we start to understand the potential and differential psychological sequelae of exposure to the virus and associated social distancing measures. Results will also have the potential to inform differential policy approaches reflecting heterogeneous impacts of the virus in various groups of the younger population in the UK, and will provide a useful evidence-base for pushing forward the development of new services addressing key NHS and public health priorities.
CHILD ANXIETY TREATMENT IN THE CONTEXT OF COVID-19 (CO-CAT): ENABLING CHILD AND ADOLESCENT MENTAL HEALTH SERVICES (CAMHS) TO PROVIDE EFFICIENT REMOTE TREATMENT FOR CHILD ANXIETY PROBLEMS
Funded by UKRI-DHSC, the Co-CAT study addresses the need for evaluation of innovations in health and social care delivery prompted by the pandemic which can be generalised and actioned in the pandemic context. Specifically this study sets out to mitigate the impact of the COVID19 outbreak on children, families and Child and Adolescent Mental Health Services (CAMHS) by evaluating an innovative, potentially cost-effective, digital intervention for child anxiety problems.
The Co-CAT team, led by Cathy Creswell (Departments of Psychiatry and Experimental Psychology) and including Mara Violato (HERC, Nuffield Department of Population Health), will conduct a multi-site randomised non-inferiority trial to establish whether a novel online, parent-led cognitive behaviour therapy program (OSI; Online Support and Intervention for child anxiety) is as effective as what CAMHS are currently delivering in the COVID-19 context and could save money. Mara will lead on the economic evaluations alongside this randomised trial.
This research has the potential to provide (i) a solution for efficient psychological treatment for child anxiety disorders while social distancing, (ii) an efficient means of treatment delivery to manage the anticipated increase in CAMHS referrals when social distancing measures are relaxed and as schools reopen, and will (iii) pave the way for high quality, efficient evaluation and implementation of digital solutions in CAMHS.
The impact of COVID-19 on people with Severe Mental Illness: Implications for Clinical Services
(Principal Investigator: Apostolos Tsiachristas. Funder: Oxford Rapid Response Fund)
Covid-19 is having a profound impact on everyone’s life, especially on people with mental health disorders. We will use routinely collected data of patients with severe mental illness (SMI) through Oxford’s Clinical Record Interactive Search (CRIS) to better understand the impact of the Covid-19 pandemic on the health and service needs of adults with severe mental illness (SMI). In detail, we will: a) assess the effect of the pandemic on mental health outcomes (including relapse, admission, self-harm and suicide), of people with SMI (psychotic disorders, schizophrenia, bipolar disorder, severe depressive disorder and others in receipt of enhanced community care), b) examine the impact of the pandemic on patients’ access to, and use of mental health services, c) identify potential effect moderators at individual, patient or service level.
Supporting Hospital and Paramedic Employees (SHAPE) during COVID: A scalable evidence based intervention with a screen and treat approach
(Co-Investigator: Apostolos Tsiachristas. Funder: Oxford Rapid Response Fund)
For frontline staff, such as intensive care unit (ICU) workers, paramedics, and call handlers, COVID presents unprecedented challenges. In collaboration with local IAPT, we will work with ICU workers (N=500), paramedics (N=800) and call handlers (N=2000) in three NHS Trusts to: (i) to reduce symptoms of PTSD and depression, including risk for suicide, by offering direct-contact wellbeing support that moves the burden of outreach to wellbeing coaches rather than frontline staff; (ii) to reduce the burden of suffering associated with PTSD and depression by identifying staff in need of treatment and prioritising their care; and (iii) to evaluate the effectiveness of these approaches and the indicative cost savings to the NHS and society.
Better Outcomes For Everybody: a pragmatic parallel randomised controlled multicentre superiority trial evaluating of the effectiveness and cost-effectiveness of a pharmacist-led intervention delivered in collaboration with physicians in asthma and COPD patients during and after COVID-19 outbreak
(Project team: Apostolos Tsiachristas and Paolo Candio. Funder: SOFAD Srl Gruppo Farvima)
Better Outcomes For Everybody (BOFE) is an international multicentre trial evaluating the effectiveness and cost-effectiveness of a bespoke pharmacist-led intervention for Asthma and COPD patients using also Artificial Intelligence (AI) and Internet of Medical Things (IoMT). Since BOFE is collecting information about the administration and results of COVID-19 testing in patients with asthma and COPD, we will investigate the impact of COVID-19 on health outcomes and costs in these patients. The study will also investigate whether IoMT had a differential treatment effect during lockdown.
THE IMPACT OF THE COVID-19 PANDEMIC ON CHILDREN AND ADOLESCENT MENTAL HEALTH SERVICES (CAMHS) INPATIENT SERVICES: A RETROSPECTIVE ANALYSES USING ROUTINELY COLLECTED ADMINISTRATIVE DATA
Apostolos Tsiachristas holds an honorary contract with Public Health England to advise/support the NHS Clinical Reference Group: Child and Adolescent Mental Health Services.
The purpose of this project is to provide senior decision makers within NHSE/PHE information on impact of COVID-19 on CAMHS inpatient services and provision. This evidence will assist policy makers and commissioners in development of support for this vulnerable group.
USEFUL LINKS
This resource was promoted at the HESG Winter 2021 Virtual conference as a useful place to publicise your COVID-19 studies.