Reliable assays that test for current and past COVID-19 infection will help control the pandemic, keep more NHS staff at the frontline and protect people with a weaker immune system – including patients with cancer. Some researchers are repurposing techniques they’ve created for early detection and diagnosis of cancer to develop innovative COVID-19 tests.
“One of the biggest problems healthcare staff face right now is to know whether or not they had COVID-19, and whether they are immune to the virus,” says Elizabeth Soilleux, senior university lecturer and honorary consultant pathologist at Addenbrooke’s Hospital in Cambridge. “They don’t know if they could be at risk, and if someone in their house has any symptoms, they have to stay off work for 2 weeks.”
Across the wider population, we need to identify and isolate asymptomatic people with the virus to control the spread of the disease and protect the most vulnerable, including people with cancer. The COVID-19 pandemic has created a backlog of people waiting for cancer screening, further tests or treatment in the UK, and substantial testing will be needed to safely maintain COVID-19-free cancer care sites.
In addition to her clinical work, Elizabeth is a research group leader at the University of Cambridge “A while ago we developed a system to sequence all the T cell receptors in a sample and predict whether someone is gluten sensitive.” Later, Elizabeth’s team repurposed the system to detect cancer. “We were awarded a Cancer Research UK (CRUK) grant to develop an assay that uses T and B cell receptor sequences to detect lymphoma. These sequences are all identical in lymphoma because they come from a single original lymphocyte, whereas they are all different if there is no lymphoma.”
Then, COVID-19 arrived. Elizabeth decided to use the approach to develop a new test to detect COVID-19 immunity. Funded by the Snudden Family Trust, a local charity, Elizabeth and her colleagues plan to sequence anonymised blood samples from healthy bone marrow donors collected at the hospital before the COVID-19 pandemic, as well as samples from patients treated for COVID-19. “We’ve got this massive freezer full of COVID-19 patient samples at the moment,” says Elizabeth.
If we see a signal, we want to do a trial comparing this test with existing COVID-19 antibody tests.
The sequencing will take place at Nonacus in Birmingham. The researchers will use a bioinformatic approach to try to identify a signal that discriminates between the two sets of samples. The assay will then need to be validated. “If we see a signal, we want to do a trial comparing this test with existing COVID-19 antibody tests, and also some longitudinal studies to find out whether immunity to COVID-19 gives long-lasting protection.”
Geylani Can is also repurposing a cancer research technique for COVID-19 testing. “My PhD at the Wellcome Trust/CRUK Gurdon Institute in Cambridge focused on DNA replication and the repair mechanisms that overcome replication problems,” says Geylani. “I developed a new assay for detection of single nucleotide polymorphisms (SNPs) that uses a very good set of enzymes, which are resistant to many chemicals and inhibitors.”
Geylani moved to Harvard Medical School in Boston a year ago to continue his work on DNA replication. He was awarded one of the inaugural AACR–CRUK Transatlantic Fellowships, but hasn’t started yet because of the pandemic. In the meantime, Geylani has been granted special permission by Harvard University to access the lab so he can work on his new test for COVID-19 diagnosis.
“Extracting RNA and trying to detect a few copies of a virus in individual samples collected from millions of people is a very challenging task,” says Geylani. “Back in February, I started thinking that we could use the enzymes of the SNP assay to detect COVID-19 RNA in patient samples, in a single reaction without the need for RNA extraction.”
Our test can quickly be modified to recognise new COVID-19 strains if the virus mutates in a dangerous way.
“We are now validating the test in patient samples, and then we will need to validate it in a real-life clinical environment,” says Geylani. “We don’t have the appropriate facilities here to work with patient samples, so I have a collaborator in Berkeley and another at the Boston Children’s Hospital who will help us do this. After we validate the test, we’re going to try to commercialise it.”
Geylani says that his test makes it possible to stay a step ahead of the virus. “In addition to normal diagnosis, our test can quickly be modified to recognise new COVID-19 strains if the virus mutates in a dangerous way.”
Geylani and Elizabeth found that they could easily transfer their expertise in molecular detection to different research fields. Alexis Webb, Research Programme Manager in our early detection and diagnosis programme, highlights the similarities between detecting cancer and detecting COVID-19, especially in people who are asymptomatic. “There are a lot of people with COVID-19 who don’t know they have the virus and are potentially spreading it. People with the earliest cancers also often don’t have any symptoms alerting them that something may be wrong. How do we understand who needs to be tested for COVID-19 or cancer and followed up?”
People with the earliest cancers also often don’t have any symptoms alerting them that something may be wrong.
Our early detection and diagnosis programme attracts people from all corners of science – including chemists, physicists and engineers – to work in this area of cancer research. Launched in 2017, the programme has funded 68 awards totalling over £20m, supporting 94 lead researchers at 34 institutions.
Geylani and Elizabeth believe that research into COVID-19 can benefit cancer research. “History is full of examples of scientific findings in one field that have had a drastic impact on another field,” comments Geylani. “By doing the work on COVID-19, we’ll learn more about the technology we’re developing for lymphoma analysis,” says Elizabeth, “so that’s a win-win situation.”