The COVID-19 outbreak 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 to answer some of the most urgent questions about the SARS-CoV-2 pathogen, from how we can improve testing, to why it’s deadly in some people but causes no symptoms in others.
This work will guide the development of new tests, vaccines, treatments and clinical strategies to help bring the COVID-19 pandemic under control.
Our COVID-19 research strategy takes a comprehensive and collaborative approach to research under five key themes:
Diagnosis – methods evaluation and development
Immunity and immunopathology – testing and mechanisms
Molecular mechanisms and target identification
Clinical epidemiology and clinical management in well subjects
Clinical epidemiology and clinical management in vulnerable populations
Caetano Reis e Sousa, Charlie Swanton, Michael Howell
The Crick has set up a testing centre 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). This service has been testing NHS staff on the frontline, providing the results and reassurance they need to know if it’s safe to perform their lifesaving duties.
Our testing methods include qRT-PCR (a laboratory-based technique to detect SARS-CoV-2 genetic material), but also others such as RT-LAMP, which do not require specialised equipment and could provide a result in just 25 minutes. This new method reacts with sections of RNA in the virus and causes the test sample to change colour if it contains the SARS-CoV-2 virus. The Crick is also testing whether the method can be used without first extracting the RNA from the test sample, which is a pre-requisite for qRT-PCR. If so, it means that, unlike conventional tests, the sample does not require much processing and the results don’t need complex analysis, which means it could be used at “point-of-care” in hospitals and care homes around the world.
We will 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.
Gitta Stockinger, Caetano Reis e Sousa, George Kassiotis, Adrian Hayday, Anne O’Garra, Samra Turajlic, Rupert Beale, Andreas Wack, Veni Papayannopoulos
Most current tests for COVID-19 detect the presence of the virus by looking for its RNA component. It is also important to be able to identify the proportion of people who have been infected and cleared the virus, and may have some degree of immunity. This will help build scientific understanding of the outbreak and guide public health decisions.
The Crick/UCLH/UCL serology initiative has developed a blood test to indicate whether someone has been infected with SARS-CoV-2. Initial results suggest that this procedure has higher levels of accuracy than other tests. It also appears to be highly scalable, with the potential to carry out thousands of tests a day.
The test is based on the use of cells expressing the SARS-CoV-2 Spike protein being analysed by flow cytometry after exposure to sérum antibodies. The flow cytometry process detects binding of antibody to SARS-CoV-2 in patients’ blood. Importantly, a second stage of the process uses neutralisation tests to see how effectively the antibodies will stop the virus from being able to infect cells.
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.
While many people with coronavirus experience mild symptoms, some end up in hospital and about 20% of these people will require critical care and possibly ventilation in an intensive care unit.
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 doctors are also seeing younger, healthy individuals decline rapidly after infection.
Some of these patients suffer from overreactive immune responses. We need to understand the causes and consequences of excessive immune responses. Our researchers will use 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 studying the differences in immune response between different groups of patients and examining how this relates to clinical outcome.
The results may be used by doctors to predict who will need intensive care and get them the treatment they need faster. A better understanding of our immune response could also aid in the development of treatments and vaccines.
John Diffley, Simon Boulton, Peter Cherepanov
Image of the ultrastructural morphology exhibited by the 2019 Novel Coronavirus (2019-nCoV) (CDC)
- CDC/ Alissa Eckert, MS; Dan Higgins, MAM / Public domainUsing 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.
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.
Charles Swanton, Steve Gamblin, Sonia Gandhi, Samra Turajlic, Mariam Jamal-Hanjani, Laura McCoy, Catherine Houlihan and Eleni Nastouli
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 between people. Some of the questions we’re investigating include - how is it spreading between healthcare workers and the public, and if people with no symptoms can spread the virus?
Understanding disease transmission patterns will help inform public health measures and limit the spread of coronavirus.
We need to understand why some individuals are affected by coronavirus more seriously than others. Studies are taking place to understand if lifestyle factors like smoking and alcohol, drug history, or ethnicity can make the disease more severe.
By understanding who is at risk, measures can be put in place to protect frontline medical workers and we’ll be better placed in case of a ‘second peak’ or future outbreak.
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)
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.
As part of the CAPTURE study, we have initiated 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.
The Crick and other vital research institutions exist to help us understand the fundamental biology underlying our health and disease. And as coronavirus continues to spread, this need has never been greater.
