By David Porteous*, Robin Flaig*, Lynn Molloy** and Nic Timpson**

Generation Scotland, University of Edinburgh* and ALSPAC, University of Bristol**

Is it really (just) a year since Wellcome kick-started the Longitudinal Population Studies (LPS) Secretariat with crucial start-up funding? In that time, have we really been able to engage with 13 diverse cohorts to assemble COVID-19 relevant questionnaires? And make these readily and freely available? Have they been picked up and used in whole or part by more than 100 studies? With more than 31,000 responses from our volunteers? The answer is a remarkable ‘yes’ to all of the above.

Since May 2020, the Steering Group has grown to 32 active members. We have met online 6 times. We have assembled questionnaires to query each of the following topics relevant to the pandemic: Physical health; Long COVID; Mental health and wellbeing; Social Circumstances; Lifestyle; Parents concerning children and young people; Personal response to the pandemic; Impact of Brexit; COVID-19 knowledge and policy; Domestic violence; Healthcare; Environmental attitudes; and coming soon, measures for Children and young people. You can access them here.

Whenever you post or publish your findings, do please reference the resource. Every bit of evidence counts when measuring the added value from the Wellcome Trust investment.

The LPS Secretariat has demonstrated like never before how agile are the UK’s broad portfolio of longitudinal population cohorts. The willingness under COVID-19 to collaborate has paid dividends, widening diversity and increasing statistical power. Anchored by pre-pandemic assessments of health and wellbeing, sociodemographic information – and biological markers in most – one key feature is our ability to measure change under COVID-19.  This vital feature has enhanced interpretation and reliability of LPS over the plethora of de novo cross-sectional studies conducted over the past year.

The LPS Secretariat has underpinned several important research publications, with many more in the pipeline. You can find them here. It has also fed into policy, through reports to Wellcome and other funder representatives on the Steering Group, and to SAGE via HDR UK.

For early stage career scientists, it has catalysed previously unimaginable levels of networking, skills, knowledge and best-practice sharing. It has provided a lifeline and lifetime opportunity for several whose research plans were stalled abruptly by the pandemic.

Alongside parallel efforts to collect valuable new COVID-19 relevant data such as serial antibody testing results, it has laid the platform for the successful and substantial bids to the National Core Studies (NCS) programme and MRC/NIMHR open call for Long COVID research proposals for Longitudinal Health and Wellbeing and Longitudinal Linkage Collaboration. Together, these efforts are not only looking to contribute meaningfully to the analysis of COVID-19 and the impact of the pandemic now, but also to leave an important legacy data set able to chart the long-term impact of this simultaneously global yet personal event. Importantly, several of the NCS analysts were themselves important contributors to the success of the LCS Secretariat.

So what next? The added value already demonstrated in such a short time surely means that as a community, we must continue and build on what has been started.  The relevance of what has already been achieved directly supports other major infrastructure platforms such as CLOSER and HDR UK. It is highly relevant to the nascent Population Research UK initiative. There are other ambitious plans brewing in UKRI which would benefit.

Wellcome made it very clear at the outset that their support was a ‘one off’ and time limited. ALSPAC and Generation Scotland will keep things going for now. We would however love to hear from others who might want to lend a hand, share some administrative assistance or help maintain, update or co-host the resource.

You can find out more from our dedicated web page or contact us at: welcomecovid-19@bristol.ac.uk

By Professor Nish Chaturvedi and Professor Jonathan Sterne 

Like many of our colleagues, each of us adapted our research from March 2020 onwards, to prioritise information that would help mitigate the impacts of the pandemic. This included asking our established population-based cohorts additional questions about COVID-19, and planning how best to harness the unique strengths of whole population anonymised health records to address key questions. Using these and other approaches, our knowledge of COVID-19 has evolved rapidly. Yet further research is required to understand the long-term health, social, and economic impacts of this disease.

The COVID-19 Longitudinal Health and Wellbeing National Core Study

In October 2020, Sir Patrick Vallance, UK Government Chief Scientific Adviser, established the National Core Studies (NCS) as part of the UK’s response to the COVID-19 pandemic. Six NCS were created focussing on key areas in which the UK needed to rapidly increase research scale to respond to the near term strategic, policy, and operational needs. These included Epidemiology and Surveillance, Clinical Trials Infrastructure, Transmission and Environment, Immunity, Data Connectivity, and Longitudinal Health and Wellbeing.

Leads for each of the NCS were approached some weeks before their launch, to articulate research gaps within their domains and devise plans to address these. We agreed that the overarching aim of the COVID-19 Longitudinal Health and Wellbeing (LH&W) NCS is to understand the health, social and economic impacts of the COVID-19 pandemic. Funding to support this major initiative was provided by UK Research and Innovation (UKRI).

The pandemic has resulted in collaborative, multidisciplinary research on an unprecedented scale and the LH&W NCS is no exception. Our team unites experts from leading institutions across the UK whose domains include epidemiology, biomedicine, social sciences, statistics, engineering and computer science. We are working to enhance and interrogate national, anonymised, integrated health records and, in parallel, longitudinal population cohorts for COVID-19 research. Participating institutions are mostly universities, but also include NHS trusts and representation from The National Institute for Health and Care Excellence (NICE). This multi-institutional collaborative team adapted to rapidly changing circumstances during the first phase of the LH&W NCS. Entering the second phase, we have 7 research themes:

UK Longitudinal Linkage Collaboration
Serology
Vaccination
Healthcare Disruption
Mental Health
Society and Health
Long COVID.

Characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19: providing the evidence base for health care services (CONVALESCENCE Study)

Although the existence of Long COVID is recognised, much remains unknown. In March 2021, we were given the go ahead to start the NIHR-UKRI funded CONVALESCENCE study. This will help to define Long COVID, its determinants and health, social and economic consequences to improve diagnosis, management and support using a combination of quantitative, qualitative and deep phenotyping approaches. Working with NICE, we will ensure that the latest evidence is passed on immediately, supporting NICE’s goal of providing ‘living guidance’ for the diagnosis and management of Long COVID.

The value of uniting established longitudinal population cohorts and national anonymised electronic health records

The team are addressing each research question by using data from established longitudinal population cohorts (led by NC) and national pseudonymised whole-population linked electronic health records (EHR ( led by JS)). These include the SAIL Databank (Wales), EAVE II (Scotland), and OpenSAFELY and the NHS Digital Trusted Research Environment Service for England, which both cover the whole of England and were established in direct response to the pandemic to enable secure, rapid analysis on primary care data linked to secondary care and COVID datasets.

Longitudinal cohorts, though smaller, have detailed pre-pandemic health and socioeconomic data, collected on all participants, where possible using objective measurement methods. This enables greater granularity of enquiry than that allowed by EHR analysis, and importantly allows us to understand how pre-pandemic factors modify disease risk and its outcomes. The UK is proudly and uniquely placed globally in the richness of its population cohorts spanning the country, covering many age and socioeconomic groups, and including hard-to-reach groups such as ethnic minorities. Renowned cohorts collaborating within the LH&W NCS include ALSPAC, BCS70, Born In Bradford , ELSA, Generation Scotland , Millennium Cohort Study , NCDS, Next Steps , NSHD , SABRE Study TwinsUK  and Understanding Society . They have been at the forefront of the UK’s response to COVID-19, and importantly include people who have not consulted with health care services.

Parallel analysis of whole-population linked EHR, which provide breadth of coverage, and in-depth data from population cohorts will provide complementary insights that enhance the robustness of our findings. By linking EHR and cohorts, we can relate the detailed, universal pre-pandemic information from cohorts to disease endpoints captured in EHR.

Although some cohorts have linked their data with EHR before the pandemic there was no unified or comprehensive approach. We have therefore established the UK Longitudinal Linkage Collaboration (UK LLC), which will unite cohort and EHR data within a single Trusted Research Environment. This key LH&W NCS initiative unites processes, minimises duplication of effort, ensures data security, and provides secure access to accredited researchers.

Impact of results

The result of this work will inform policies to help mitigate the impacts of the pandemic on health and society. To date we have provided policy makers and NICE with vital information on:
• Long COVID risk factors https://www.medrxiv.org/content/10.1101/2021.06.24.21259277v1
• Long COVID GP coding differences https://bjgp.org/content/early/2021/06/28/BJGP.2021.0301
• The effect of the pandemic on mental health https://www.medrxiv.org/content/10.1101/2021.03.26.21254424v2
• The significance of pre-pandemic mental health on health care disruptions https://www.medrxiv.org/content/10.1101/2021.04.01.21254765v1
• How government initiatives such as the furlough scheme have affected health and wellbeing https://www.medrxiv.org/content/10.1101/2021.06.08.21258531v1
• Inequalities in healthcare disruption  https://www.medrxiv.org/content/10.1101/2021.06.08.21258546v1

These outputs provide early evidence of the value and impact of this kind of multi-disciplinary, inter-institutional, cross platform approach to answering a broad range of key questions.