The SARS-CoV2 Immunity and Reinfection Evaluation Study (SIREN) celebrated its two-year anniversary earlier this year. SIREN was established early on in the COVID-19 pandemic to monitor COVID-19 infections and the immune response in healthcare workers. The study has engaged with almost 45,000 participants across the UK who provide regular samples for testing, making SIREN the largest study of its kind anywhere in the world.
Collaboration is key
The scale and ambition of the study set it apart from the beginning, as did its unwavering commitment to collaborate on a large scale. SIREN operates in collaboration with 135 NHS hospital sites, as well as all four UK public health agencies: The UK Health Security Agency, Public Health Scotland, Public Health Wales and HSC Public Health Agency in Northern Ireland. In two years, it has carried out over a million PCR tests and more than 400,000 blood tests.
The SIREN consortium, created in August 2021, is a group of 13 different bodies and organisations that each bring something unique to the study, and who are celebrating a milestone of their own: one year since a £1.57 million grant was awarded by UK Research and Innovation to enable the consortium to investigate breakthrough infections and vaccination effectiveness.
“We knew we needed to be inherently collaborative from the very start,” says SIREN study Lead and Consultant Epidemiologist Victoria Hall. “If we had tried to make the study work first and then focused on collaboration as an afterthought, it simply wouldn’t have worked. We recognised that we had a unique opportunity to bring together all the partners we needed at the outset to create an extraordinarily multidisciplinary team that could organise itself to answer the pressing questions we faced.
We also knew that, to make it work in the time we had, we’d need to capitalise on pre-existing infrastructure and ways of working. We didn’t have the luxury of being able to start things from scratch – we had to be flexible and adapt to our environment as it changed around us.”
At a practical level, working as a consortium has made collaborating with others much easier. For example, the team has worked with The Francis Crick Institute, Humoral Immune Correlates for COVID19 (HICC) and the G2P-UK National Virology Consortium on its analyses of reinfection and vaccine breakthrough. “It was a huge advantage to be able to easily bring together different assays and expertise in this way,” says Victoria. “The team at the Crick were able to do high-throughput live virus neutralisation, while our colleagues at G2P could give us detailed characterisation of individual cases.”
Seeking opportunities
SIREN has consistently sought to create new opportunities. It has paved the way for subsequent studies PITCH and VIBRANT, which are ‘nested’ within it, while having their own specific research focus – T cell responses in the case of PITCH and breakthrough infections and immune failure in the case of VIBRANT.
PITCH (Protective Immunity from T Cells in Healthcare workers) operates in six sites – Oxford, Birmingham, Sheffield, Liverpool, Newcastle and Cambridge – and has recruited over 2,000 healthcare workers to study the immune response to SARS-CoV-2 vaccines and infections in greater depth. These participants are now beginning their third year of follow-up, and the data they provide will help uncover vital evidence about immunity to future variants and the need for future booster vaccines. In addition, many regional and national studies involving immunocompromised people (including the OCTAVE study) collaborate with PITCH to provide control samples.
VIBRANT (Vaccine Immunity Breakthrough & Reinfection: Antibodies and T cells) is comparing data from healthcare workers (enrolled in either SIREN or PITCH) who have experienced vaccine breakthrough infections with data from people with no vaccine breakthrough infections, in order to identify individual features, health conditions and deeper immune system characteristics that are risk factors for reinfection. Due to the high numbers of people infected with Omicron, studying the people who don’t get COVID-19 is increasingly important.
One eye on the horizon
Throughout the study, the team has been conscious of the need to ensure that its outputs, wide-ranging as they are, are useful and can be made available for others in future.
“We were thinking from a very early stage about how to ensure everything we were doing would have maximum impact in the future,” says Victoria. “We were gathering valuable data and knowledge, while developing new ways of working – all of which have applications for future research relating to COVID-19 and more widely.”
But that’s not to say the study is winding down by any means. On the contrary, the questions it aims to tackle have multiplied over time.
“There is so much still to do,” says Victoria. “Our areas of interest are continuing to evolve. We have looked at initial infections and explored immunity from previous infection, vaccines or both, but we are also keen to look at people who have never had an infection and the longer-term picture. It’s still vital to understand the underlying immunology, and there are many questions still unanswered. One of the key things we still want to do is truly understand what optimum protection looks like.”
Long covid is increasingly a priority, and the study team have begun investigating its prevalence in the study cohort with a view to exploring the immunology underpinning it.
SIREN also continues to have a vital surveillance function, which will be especially important over the autumn and winter months, when pressure is likely to mount on front-line health workers as they tackle challenges such as flu and infection control.
These future priorities mean that those who have been diligently giving samples for two years can continue to play a part in answering the big questions about COVID-19.
“Our participants are the life blood of the study,” says Victoria. “There will be many opportunities for them to be involved for longer, and to continue to be part of the SIREN study family.”
SIREN has this week launched videos charting the story so far, which features researchers, doctors and participants giving their perspective on being involved in the study.