Having systems in place to keep track of new and existing infectious diseases has always been an important aspect of human health. The onset of the COVID-19 pandemic meant that we needed a whole new set of processes to deal with pandemic surveillance.
Influenza virus - Peter Rosenthal
Public health surveillance is an idea that’s been around for a long time, and our ability to detect and deter potential risks from infectious diseases continues to improve as we continue to learn more about how diseases evolve and spread.
The Crick houses the Worldwide Influenza Centre, one of six WHO collaborating centres located across the globe that cover seasonal flu, in addition to a seventh centre that covers zoonotic flu. Together these centres monitor data from around the world to track how flu strains are evolving and predict which strains will become the most dominant that season. They receive samples from the network of National Influenza Centres, who in turn receive samples from GP surgeries and hospitals in their respective countries. Because the regulation and licensing around the seasonal flu vaccine are so well-established, vaccines can be created for new strains very quickly.
It takes around six months for flu vaccines to be developed and manufactured at the necessary scale. Members from each of the six collaborating centres gather twice a year to look at data on different strains from around the world, and use the data to decide which strains to include in that season’s vaccine. The final vaccine doesn’t include the whole virus, just the spike proteins, so the vaccines aren’t infectious and won’t cause any illness.
There are a few different ways in which seasonal influenza vaccines are created. In some cases scientists might create a modified version of the virus that can be used to safely develop a vaccine. Dr Ruth Harvey, assistant director of the WIC at the Crick, explains that these are effectively “designer viruses”. These viruses are particularly useful when looking at avian flu viruses that could pose a pandemic-level threat to humans.
The COVID-19 pandemic
The COVID-19 pandemic was unlike anything in recent history. We knew very little about the virus at first, and there was a rush to learn as much as we could as quickly as possible to inform public health decisions that would have a massive impact on the lives of us all.
“The Crick was in a unique position. We already had people with a range of expertise in different areas, and leadership had the oversight to know exactly where everyone fit,” Ruth points out.
Dr Mary Wu, who worked in the Crick’s High-Throughput Screening team at the time, was one of many researchers who shifted their focus towards COVID-19. She first helped set up the Crick’s PCR testing pipeline, in partnership with colleagues at UCLH, the Crick’s local hospital, which after just four weeks was able to process 1,000 tests a day.
Mary then worked with Ruth and the WIC to develop a new type of neutralisation assay. Neutralisation assays are a way of testing samples, for example drugs or blood serum from patients, to see how effective they are at blocking infection by specific viral variants. The high-throughput microneutralisation assay (HTmNA) that Mary helped develop can handle 1,200 samples against three different variants in a week. This is a huge improvement over traditional neutralisation assays, which can only handle around 100 samples against a single variant in the same amount of time. The assay has been in such high demand, it has now moved to the newly formed Crick Covid Surveillance Unit.
The Legacy Study
Following on from this, the Legacy study was set up, a partnership between the UCLH Biomedical Research Centre and the Crick . The study’s aims were to use the large amounts of data being collected from the newly-established testing pipeline, as well as running samples from willing participants through the new HTmNA to better understand how people could be protected against COVID-19. A quarter of all Crick staff are still participating in the study, which continues to collect important data about the virus. The team behind the study is now looking for data about the protection offered by a fourth vaccine dose.
It’s difficult to overstate the lengths to which the team working on the Legacy study went in order to get the data the need. Legacy study clinical lead Dr Emma Wall recounts a situation where the team needed a blood sample from someone infected with the Omicron variant, which had only recently been discovered at the time. She managed to contact a participant from the study who matched the criteria, a Crick employee who was still contagious and self-isolating.
After obtaining consent, Emma went to their house to take a blood sample. The sample went back to be analysed that day. “It is amazing to have research participants who are scientists,” Emma notes, “they’ll just go for it!”
The amount and variety of partnerships that have come out of the Crick’s testing pipeline and Legacy study are substantial. Emma and her team worked closely with government to advise on vaccine and treatment policy for COVID-19, as well as pharmaceutical companies to help them gather data for their clinical trials. They’ve also partnered with national studies on COVID-19, including the UCL Virus Watch study, SIREN study and OCTAVE-DUO, providing them with data from the HTmNA and helping to identify emerging variants. Of course, they’re also sharing data and maintaining close ties with the NHS, and have incorporated NHS workers into the Legacy study. New partnerships have also formed within the Crick, like group leader Prof. Samra Turajlic’s CAPTURE study.
The future of pandemic surveillance
Although many of the resources and research that initially pivoted towards COVID-19 have shifted back the other way, the lessons we’ve learned and partnerships that we have formed should make us better prepared for future pandemics. In the wake of the 2009 H1N1 pandemic, there was a shift in the way flu samples were processed by the Centers for Disease Control in the US, and important lessons were learned in effectively communicating information about transmissible diseases to the public.
One interesting side effect of the pandemic is the huge decline in flu cases observed over the last few years. Researchers aren’t sure on the exact reasons for this, although it was likely helped by the decrease in social contact, but there could be other reasons related to similarities in the way our immune systems interact with each virus. Ruth and the rest of the WIC team will be keeping a close eye on how this interaction plays out going forwards.