Coronavirus (COVID-19) research

Covid-19 diagnosis – methods evaluation and development

Michael Howell, Caetano Reis e Sousa, Charlie Swanton

How can we improve diagnostic testing?  

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.

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

How do we know who may need intensive care? 

Some patients with COVID-19 suffer from overreactive 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. 

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 team’s approaches are also being used to test whether COVID-19 vaccines are effective in cancer patients. 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.

COVID-19 molecular mechanisms and target identification

John Diffley, Simon Boulton, Peter Cherepanov

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. 

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

How is the coronavirus spreading? 

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.

Who is vulnerable to infection? 

We are working with UCL and UCLH on the Legacy Study, to help understand how and why people are vulnerable to infection with SARS-CoV - how the virus is transmitted between people, how later stages of the disease develop and how the body’s immune system attempts to control the virus.

As more people are vaccinated across the UK, we will investigate changes in the immune system, and uncover possible reasons for re-infection in participants who are vaccinated. 

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.

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 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.

CAPTURE Study

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 October 2021, we published results finding that only 54% of cancer patients (31% of patients with blood cancer and 62% of patients with solid cancers) developed neutralising antibodies for the Delta variant, after two doses of COVID-19 vaccine.
• Neutralising antibody responses against this variant were higher in vaccinated who had also previously been infected with SARS-CoV-2, compared with those who had no previous infection (57% compared with 31% for patients with blood cancers; and 86% compared with 62% for patients with solid cancers).
• The findings suggests that cancer patients, especially blood cancer patients) would benefit from a third dose of the vaccine.
• These findings have been submitted to the JCVI, as evidence of the level of protection cancer patients have against the variants of concern.
  • Read more about these findings here

The researchers are continuing this area of research, looking at how the pandemic is effecting people with cancer.

SOAP Study 

The SOAP Study, a collaboration funded by Cancer Research UK, looks at people with cancer to see if their immune system responds differently to the coronavirus and if there are any long-term effects. 

Research suggests that patients with blood cancers such as leukaemia vary widely in their immune response to COVID-19 and can struggle to clear infection for many weeks. By contrast, most patients with solid tumours, even those with advanced cancer, could mount an effective and lasting immune defence.

The next phase of the study will be monitoring the immune response of people with cancer to the COVID-19 vaccine.