What were your ‘day jobs’ this time last year?
Maggie: I'm a PhD student, studying bladder cancer. I have a clinical background and a lot of my work in the first year of my PhD focused on coordinating the journey of patient samples from the clinic to the lab, where we would process them.
Irene: Before the pandemic, I was wrapping up a project studying immune cells in samples from patients with breast cancer. I was creating and refining flow cytometry panels that would allow patients’ immune responses to be studied using different equipment in different hospitals and get comparable results. My next steps would have been to diversify the selection of samples that we were examining with these panels, but the early stages of the pandemic put this work on hold.
Leticia: I’m a postdoc, and I was mainly based at the Crick before the pandemic. I was looking at a particular type of immune cell called Gamma Delta T cells and trying to understand the signals that regulate these cells, how the cells develop, and how they fight off infection in the female reproductive tract.
How did you first get involved in researching COVID-19?
Leticia: In mid-March, when we began to see the impact of the pandemic, Adrian Hayday got in touch and asked whether we would be interested in using our immunological background to try to learn more about the disease. We quickly began the COVID-IP (COVID immunophenotyping) project, examining the different immune cells in the blood of patients with COVID-19 and investigating whether they could indicate how severely ill each patient would become.
Irene: I came to the COVID-IP project in a similar way – Adrian contacted me with some information about potential COVID-19 research, and suggested that we might be able to repurpose the panels I had developed.
Maggie: Alongside people like Abhi Das, Yin Wu and Dan Davies, I’m part of a whole group of people in the lab who have clinical backgrounds. In COVID-IP, we’ve been involved in everything from setting up the ethics approval, to practical things like sourcing healthy control patients and actually getting the blood samples.
We’re able to see how patients are doing in the clinic, and use that information to guide the research project. We can advise on which questions to ask and which comparisons to make.
Can you tell us a bit more about beginning to study cancer patients specifically?
Maggie: Half of our lab are based at Guy’s campus, which is a hub for cancer research and treatment. During the lockdown in April, there were lots of clinicians whose cancer patients had been affected by lockdown, and lots of lab-based researchers whose usual work had been shut down and wanted to help.
Leticia: SOAP, led by Sheeba Irshad, is a project studying the immune response to COVID-19 in cancer patients specifically. People with cancer were told to shield in March last year. It was a decision that has had a huge impact on their healthcare but it wasn’t necessarily driven by data, partly because the virus was so new. There was an assumption that cancer patients would be more susceptible to the virus, and SOAP was set up to test that assumption.
Some of us in the lab initially came on board to provide some technical assistance with the project. A natural collaboration started to emerge and it’s a real team effort now.
What has the project found?
Leticia: We found that patients with solid cancers – cancers that cause solid lumps – could actually mount a similar immune response to an otherwise healthy person. They created long-lasting antibodies and began to test negative for the virus within two or three weeks after the initial infection. However, patients with blood cancers like leukaemia tested positive for much longer and their antibody response was delayed or absent.
Irene: We also saw some differences in the recovery of lymphocyte numbers in patients. In patients with solid cancers, you see a decrease in T cells around the time of the initial infection, but after four to six weeks of negative tests, they went back to normal levels. For patients with blood cancers, it took much longer for their immune system to get back to its original, pre-COVID state; in fact, it’s not always clear that it’s got there yet.
Irene del Molino del Barrio
And do you hope that this could eventually guide policy?
Leticia: We would love to contribute to new guidance, but we’ve only studied around 50 patients so far, and it wouldn’t be reasonable to come up with new guidance based on that. We want to provide data that could enable people to make more rational choices when it comes to shielding or vaccination policy in the future.
Maggie: Exactly – even though we have a convincing study, it’s not enough to change policy in the short term. But I hope that we’re producing data that challenges preconceptions about cancer patients’ needs.
Even coming from an oncology background, I was surprised to see that groups of cancer patients had similar immune responses to otherwise healthy people. We often see implicit assumptions about the fragility of cancer patients’ immune systems, and hopefully this study will be one step towards challenging those assumptions.
How have you found being involved with the project?
Irene: It’s been humbling to be able to contribute to a larger effort – despite all the late nights and stress! The project has brought together so many capable people and we’re moving at an incredibly fast pace. I don’t think I’ve ever seen anything like it before.
Maggie: When I started my PhD project, I think it took around six months to get ethics approval for my work and set up the pipeline that we would be using to analyse the samples. And that wasn’t seen as particularly slow! This time, it took around three weeks from the first mention of the project to our first sample.
Even though we were all part of the same team before this, this is the first time that we’ve all worked together towards the same goal. We’ve been thrown in together at all hours of the day and night and it’s strengthened how we work as a team.
And what are your plans for the next stages?
Leticia: When we started looking at the immune response to COVID-19 in cancer patients, the obvious next question was their immune response to COVID-19 vaccines.
Irene: At the end of last year, we kicked off a new project to study whether cancer patients who receive COVID-19 vaccines have the same strong immune response as otherwise healthy people, and whether that immune response lasts as long.
When I talk to clinicians at Guy’s and St Thomas’s, vaccination roll-out is obviously at the top of people’s minds. Oncologists want to know how to advise their patients about vaccination, but there isn’t the data to do that at the moment. We’re hoping to fill in some of those gaps.
COVID-IP and SOAP are possible thanks to support from the KCL Charity, the Medical Research Council, Cancer Research UK, Breast Cancer Now, Wellcome, the Rosetrees Trust, the John Black Charitable Foundation, the Cancer Research UK Cancer Immunotherapy Accelerator and the UK COVID-Immunology-Consortium.