Samra Turajlic's lab working on the CAPTURE project, part of the Francis Crick Institute's COVID-19 research.

Coronavirus (COVID-19) research

Intro

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The COVID-19 pandemic requires a concerted research effort that draws on a range of different disciplines. Francis Crick Institute researchers are working at the forefront of the scientific response, answering some of the most urgent questions about the SARS-CoV-2 pathogen.

At the Crick, our world-leading research expertise, facilities and flexibility put us in a unique position to help. We're collaborating in multi-disciplinary teams, with researchers, clinicians and partners to help answer key questions: from why it’s deadly in some people but causes no symptoms in others, to how the virus is evolving and the threats from new variants.  

This work will guide the development of new tests, vaccines, treatments and clinical strategies.

    COVID-19 research themes

    1. How can we compare and improve testing methods?

    Diagnosis – methods evaluation and development

    Our testing service helps local hospitals and care homes remain open and safe, and allows us to continue our vital research. We are using our experience to compare and evaluate testing methods, and to help improve clinical diagnostic testing.

    Improving testing

    2. Why are some cases so much worse than others?

    Immunity and immunopathology – testing and mechanisms

    We’re investigating how our immune system responds to the coronavirus, why some cases are much worse than others, and if immunity, induced by vaccination or infection with the original SARS-CoV-2 strain, can protect against new variants.

     

    Understanding immunity

    3. How does the virus interact with our cells?

    Molecular mechanisms and target identification

    Using the Crick’s world-class expertise in virology, structural biology, and chemistry, we are investigating the lifecycle of the coronavirus, how it attaches to cell surfaces, enters cells, and replicates. This could help identify potential drugs and treatments.

    How it works

    4. How is coronavirus evolving and being transmitted?

    Clinical epidemiology and clinical management in well subjects

    We’re investigating how the coronavirus is evolving and spreading between people, including how effective vaccines are against new variants of SARS-CoV-2. 

    Transmission and evolution

    5. How is coronavirus affecting people who are already ill?

    Clinical epidemiology and clinical management in vulnerable populations

    We’re using our extensive expertise in cancer immunology and infection to investigate the immune response to coronavirus in cancer patients, how this is affected by vaccination and the impact of the new SARS-CoV-2 variants. 

    Coronavirus and cancer

    1. How can we compare and improve testing methods?

    Covid-19 diagnosis – methods evaluation and development 

    Michael HowellCaetano Reis e Sousa, Charlie Swanton

    How can we improve diagnostic testing?  

    A short film about how our testing programme came about. Thank you to all our staff and partners who made this work possible.

    The Crick rapidly set up a testing centre in April 2020 for SARS-CoV-2 - the virus that causes COVID-19 - in collaboration with University College London Hospitals (UCLH) NHS Foundation Trust and its diagnostic partner Health Services Laboratories (HSL). Our testing service helps local hospitals and care homes remain open and safe for staff and patients. It has also allowed us to safely continue our vital research for both COVID-19 and our wider work.

    Our testing methods include qRT-PCR (a laboratory-based technique to detect SARS-CoV-2 genetic material), and others such as RT-LAMP, which do not require specialised equipment and are faster. The Crick is trying to build a device based on RT-LAMP that could be used at “point-of-care” in hospitals and care homes around the world. 

    We will continue to use our experience to compare and evaluate testing methods, and improve clinical diagnostic testing. Validation of these methods will be useful not only for patient diagnosis and screening of health workers, but also for future screening of populations for virus prevalence.

     Find out more about how we set up our testing pipeline at the start of the pandemic.

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    2. Why are some cases so much worse than others?

    Covid-19 immunity and immunopathology – testing and mechanisms

    Gitta Stockinger, Caetano Reis e Sousa, George Kassiotis, Adrian Hayday, Anne O’Garra, Samra Turajlic, Rupert Beale, Andreas Wack, Veni Papayannopoulos

    Researcher looking at a screen with results about basophil levels in COVID-19 patients.

    How can we tell who’s already had the virus?

    The Crick/UCLH/UCL serology initiative has developed a blood test to indicate whether someone has been infected with SARS-CoV-2. 
    The Crick’s expertise in flow cytometry and neutralisation assays (tests that measure how effective different antibodies are at preventing infection), offer a high level of accuracy and provide powerful insights into patients’ immune response to infection. 

    The information from our tests could be used to quickly determine the effectiveness of candidate vaccines. It will also be used for research studies seeking to establish levels of infection across large groups of people and to find out how long immunity to SARS-CoV-2 might last. 

    Find out more about coronavirus antibody tests and what we know so far

    Why are some cases much worse than others?

    Patients who die of COVID-19 often succumb to pneumonia, leading to respiratory failure. Many of these patients are older or have existing health conditions, but some younger, healthy individuals decline rapidly after infection.

    Some patients suffer from overreactive immune responses. We need to understand the causes and consequences of excessive immune responses. Our researchers are using their substantial expertise in inflammation research, tissue repair and virology, to study why some people can’t get rid of the infection after a few days and why some people enter a type of ‘immune shock’ where inflammatory cells cause the body to shut down. 

    Watch our Instagram Q&A to meet one of our researchers and explore our work to understand the immune response to SARS-CoV-2.

    How do we know who may need intensive care? 

    The Crick, King’s College London and Guy's and St Thomas' NHS Foundation Trust have built a high-throughput platform, looking at patient’s blood over time to see how our immune system responds to coronavirus, and if there are clues to whether someone might need additional treatment. 

    The team has previously run large studies monitoring how people’s immune systems respond to flu vaccines, and have developed new methods for tracking patients’ immune response. In the new platform, they are identifying so-called ‘immune response markers’ that differentiate patients according to their disease severity. 

    The results have led to a collaborative study with public health statisticians, to investigate if those ‘markers’ offer an improved way for doctors to predict which patients are likely to need intensive care and to get them the treatment they need faster. The results are expected in February 2021.  

    The team’s approaches are also being used to test whether COVID-19 vaccines are effective in cancer patients, who need to visit hospitals frequently, but who are often considered to have weak immune systems. 

    Find out more about the COVID-IP project.

    What are the threats from the new SARS-CoV-2 variants?

    The Crick is investigating the degree of cross-reaction and cross-protection between the new variants, and also between common cold coronaviruses and SARS-CoV-2. We are specifically investigating if immunity, induced by infection or vaccination with the original strain, can protect against new variants. Currently, we are focussing on the new variants that emerged in the UK, South Africa and Brazil.

    We are also preparing for further mutations and new variants of SARS-CoV-2 that may not respond to the current vaccines, or for future zoonotic (spread between animals and people) introductions of novel coronaviruses. 

    We are testing a vaccine in preclinical models that trains the immune system to recognise all coronaviruses and variants thereof - a pan-coronavirus vaccine. This is based on our earlier discovery that some antibodies, created during infection with common colds, can also target SARS-CoV-2.

    Find out more about the national research project to study the effects of emerging SARS-CoV-2 variants.

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    3. How does the virus interact with our cells?

    COVID-19 molecular mechanisms and target identification

    John Diffley, Simon Boulton, Peter Cherepanov

    How can we find new drugs to treat COVID-19?

    How does the virus infect our cells? 

    Using the Crick’s world-class expertise in virology, structural biology, and chemistry, we want to understand the lifecycle of the virus – how SARS-CoV-2 attaches to cell surfaces, how it enters cells, and how it replicates inside cells. By knowing more about how the virus operates, we hope to identify potential drugs that interfere with stages of this lifecycle. 

    Teams from all across the Crick specialise in studying different parts of this process, and we are looking at how the virus interacts with human cells from every angle. By drawing on years of expertise studying viruses like HIV and influenza, we will use a combination of techniques including high-resolution imaging and genetic editing methods like CRISPR to build up a picture of how SARS-CoV-2 and our cells interact.

    How can we use this information to identify potential treatments?

    We already have long-standing partnerships with pharmaceutical companies like AstraZeneca, GSK and MSD, and industry scientists work closely alongside Crick researchers to speed up the discovery and development of new treatments

    Teams across the Crick are collaborating to create methods for systematically testing an array of options (including drugs and antibodies) that might block the virus entering cells, or limit its ability to replicate once inside the cell. 

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    4. How is coronavirus evolving and being transmitted?

    Clinical epidemiology and clinical management in well subjects

    Charles Swanton, Steve Gamblin, Sonia Gandhi, Samra Turajlic, Mariam Jamal-Hanjani, Laura McCoy, Catherine Houlihan and Eleni Nastouli

    Steve Gamblin's Lab working on COVID-19 research

    How is the coronavirus transmitted? 

    Through the Crick COVID-19 Consortium and our strong partnerships with organisations including University College London Hospitals (UCLH), we’re conducting studies to understand how coronavirus is evolving and being transmitted. Find out more about our SAFER study - investigating how COVID-19 is spreading between healthcare workers and the public, to help protect staff and their patients.

    Understanding disease transmission patterns will help inform public health measures and limit the spread of coronavirus.

    How is the coronavirus evolving?

    We are taking part in a new national research project to study the effects of emerging SARS-CoV-2 variants. 

    The research is part of the ‘G2P-UK’ National Virology Consortium, which brings together leading virologists from 10 UK research institutions to study new mutations in the virus. They will flag the riskiest variants as they arise, such as those associated with fast spreading virus clusters, and will create versions of the virus with and without each mutation, so they can study the effects of each change individually.

    They will find out how and understand why these variants differ, including in regards to: how transmissible they are, the severity of COVID-19 they cause and the effectiveness of vaccines and treatments against them.

    Find out more about the national research project.

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    5. How is coronavirus affecting people who are already ill?

    Clinical epidemiology and clinical management in vulnerable populations

    Samra Turajlic, Charles Swanton, Julian Downward, George Kassiotis, Adrian Hayday, Katie Bentley, Robert Wilkinson, Anne O’Garra, Dinis Calado, Anthony Swerdlow (Head of Epidemiology, Royal Marsden/ICR), Christina Messiou (COVID-19 Radiomics, Royal Marsden/ICR)

    How do cancer and treatments like chemotherapy, immunotherapy and radiotherapy change how the body responds to coronavirus?

    How is coronavirus affecting people with cancer?

    COVID-19 is creating unprecedented challenges for clinicians delivering cancer care. Cancer treatments - surgery, radiation, chemotherapy, and immunotherapy - play a crucial role in curing and controlling cancer, but we don’t know how they affect the patients’ ability to mount an immune response to the virus. Currently, many treatments are being delayed because of the potential risk.

    The Crick is using our extensive expertise in cancer immunology and infection to investigate the immune response to SARS-CoV-2 in cancer patients and untangle what is bound to be a complex relationship between the host, the cancer, the virus and the anti-cancer therapy. 

    In the current phase of the project, we are extending our analysis to investigate the immune response after vaccination.

    As part of the CAPTURE study, we are running a large prospective immune-monitoring trial with patients at the Royal Marsden NHS Foundation Trust.

    • In the short term, we want to understand the true proportion of cancer patients that have been affected by COVID-19, including those without symptoms or who may have already recovered. 
    • Longer term, the study aims to determine how cancer type, disease stage, different cancer treatments, host genetics and host immune response could affect the severity of a patient’s infection and their chance of survival and the impact on their cancer.

    This will help inform desperately needed clinical guidance, avoid long-term impacts on cancer patients, and help protect vulnerable people in hospitals.

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