Leticia: At the beginning of March, the scale of the impact of the virus became apparent. So on the fifteenth of March, we officially put all our other work on hold and began setting up our new project with Guy’s and St Thomas’s Hospital. We are trying to understand at a basic level why some patients with the virus don’t show any symptoms at all, while others need to be hospitalised and some sadly die.
As we learnt more about the virus in the early stages, we realised that we had the tools and knowledge to investigate how SARS-CoV-2 interacts with patients’ immune systems. This is one of the big unanswered questions about the virus, and could explain why people react so differently. We’ve led similar projects in the past, monitoring people’s response to flu vaccines, and tracking immune responses in mice on a large scale, so we felt that the lab was well-placed to take on this project.
This project was unique to anything else we had worked on: it was an opportunity to work with clinicians to examine patients in real time, we had to carry out the initial studies in a high-containment facility, and the need for answers was urgent.
We take blood samples from hospitalised patients at different points in time and measure the proportions of different immune cells, as well as molecules that cause the immune response called inflammatory mediators, and compare this to their symptoms. This lets us build up a picture of how the immune system responds in patients with both mild and severe symptoms.
Our work may show ways to treat patients with drugs that already exist, and could identify features of the immune response that we would want to boost, tying in with the vaccination strategies under development.
Miguel: It’s been a difficult project to set up. We processed our first samples on the twenty-fifth of March, ten days after we started, and in those early days, it was a small team of five running everything. We developed the process and we were receiving the samples, processing them and analysing them ourselves. We’re now up to a team of 16 people and we’re able to divide the work.
We work in shifts in the lab, and we can spend some time outside the lab focusing on data analysis and finding results in the information that we’ve gathered so far.
Leticia: My postdoc project is focused on a type of immune cells called gamma delta T cells. I’m examining how these cells develop and how they behave in tissues. One part of my project focuses on the female reproductive tract, where they play a role in protecting against infection.
Miguel: I’m also working on gamma delta T cells, studying how they interact with other groups of cells, like alpha beta T cells in different scenarios.
Miguel: No. Not at all. This is something that we could do to directly help society. I felt that if we could help, we had to do it.
Leticia: It’s reassuring in a way that the same techniques we use every day could have a major impact on human health. I’d make the decision again in a heartbeat.
Miguel and Leticia in the containment facility before sample processing.
Leticia: We’re processing blood from people infected with the virus in the containment level 3 facility at King’s College London. Originally, there were just two of us analysing the samples but we’ve now trained four more people, and we can rotate and take turns.
Even though we’re not going in every day now, there’s still a huge amount to do away from the facility. We’re analysing the data and establishing patterns and trends.
Miguel: This project has been a great way to see how different institutes can come together. We’ve always had collaborators but now we’re working seamlessly. The team is a mixture of scientists from the Crick and King’s and as an international team with expertise from different areas of science, we’re able to work effectively in completely new ways.
When we are analysing samples, we use the facilities at King’s but we are also building on the strengths of the Crick. For example, we are using a tool to measure gene expression called NanoString in collaboration with Maria Greco.
Before all this started, we were working on a project with Francesca Di Rosa at the Institute of Molecular Biology and Pathology in Rome, focused on ways to monitor and track the immune system in human diseases. We’ve been able to apply these findings almost immediately, and everyone involved is so keen to contribute any way they can.
Leticia: I agree – we’re working at a completely different pace. When you’re involved in basic research, you accept that your work may or may not have a direct impact on human health, and if it does it will probably be many years later. At the moment, our team and others around the world have an opportunity to have an impact very, very quickly using the same skills that we’ve been honing for years.
Miguel: We communicate our experiments and our results in a totally different way. Normally, we gather data, present it in a paper and publish a finished project. We’re now gathering information as quickly as possible and then also sharing it as quickly as possible. Everyone seems to have woken up to the fact that it is in all our interests to have as much information as possible publicly available. In the scientific community, it has transformed collaboration and allowed us to bring expertise together on a huge scale. We’re working with the European Bioinformatics Institute to make the data publicly available, and soon other people will be able to benefit from this resource that we’re creating.
The COVID-IP team during a team meeting over Zoom.
On the other hand, it’s made it even harder for someone who doesn’t work in science to see what a ‘legitimate’ article is. I wouldn’t be surprised if a lot of scientists feel more of a responsibility to be publicly available to answer questions and dispel myths about the virus.
Leticia: We want to analyse as many samples as possible to be able to draw useful conclusions from them. There are so many people involved in this project, but two of the most important groups are the patients who donate their blood to us, and the team of research nurses who engage with the patients, explain the project to them, obtain their consent and take the blood samples. Without them, there’s no way that we’d be able to get meaningful results in such a short period of time.
In the long run, understanding immunity to SARS-CoV-2 will not only be crucial in our response to this pandemic, but will be central in our response to other infections that might emerge in the future.
This collaboration has worked so effectively thanks to how much everyone wants to contribute – the team of researchers at the Crick and King’s College London, the clinical teams at Guy’s and St Thomas’s, and our funders King’s Together, Cancer Research UK, Wellcome, the H2020 MSCA programme, EMBO, Rosetrees Trust and John Black Charitable Foundation.
