The PERFORM consortium are optimistic their novel diagnostic approaches can accelerate the understanding of COVID-19.
Photo by Tim Rouen
It has been a trying time, many aspects of our lives have changed and as we move towards an endzone, the rhetoric of ‘back to normal’ seems more likely to be a normal, version 2.0. Many research projects, especially those involving clinical research, have been abruptly stopped in their tracks by COVID-19. However the consortia of PERFORM and its cousin EU-funded project, DIAMONDS (commenced January 2020) have rapidly adapted to apply their expertise to tackling this new virus.
As COVID-19 began to spread rapidly through Europe, many Universities and research laboratories shut down to prevent the spread of the virus. The PERFORM and DIAMONDS consortia had to rapidly adjust and many staff switched to working from home while many of the clinical research staff were called back to help on wards and intensive care units. Dr Ruud Nijman, NIHR academic clinical lecturer at Imperial College London in the UK told us “I was anticipating to spend most of my time working on PERFORM and DIAMONDS related projects over the next few months; however, when the COVID-19 pandemic reached London, I was asked to support the clinical frontline teams”. For Prof Federico Martinón-Torres, - Head of Translational Paediatrics and Infectious Diseases at the Hospital Clínico Universitario de Santiago in Spain who runs the clinical trials for PERFORM and DIAMONDS – the challenge has been extraordinary, "COVID-19 prompts all of us to think, work and suffer together relentlessly”. Consortia members are making extraordinary efforts, not only to continue as much as possible the existing work, but also to use the infrastructure of PERFORM and DIAMONDS to tackle COVID-19. For Dr Victoria Wright, PERFORM and DIAMONDS scientific manager at Imperial College, it seemed at first like a huge logistical challenge but “having a great team of dedicated people is making all the difference.”
A familiar problem
The message that “testing is key” has been repeated time and time again by scientists, politicians and the media. But those caring for patients with COVID-19 realised quickly that the current tests are imperfect. For example, there are patients with typical features of COVID-19 who repeatedly test negative. This is a familiar problem the consortia face. In their preceding EU-funded EUCLIDS project (GA 279185) the research team found that more than half of children who had features of a very severe infection tested negative for suspected pathogens. This is why PERFORM and DIAMONDS are using a novel approach to diagnosis, which is based on detecting the body’s response to the infection rather than detecting the bacteria or viruses that cause it. This approach looks at genes which are switched on and off in the blood – a so called ‘gene signature’ – which is unique to each type of infection. The consortia instantly realised that they could apply the same approach to COVID-19. Dr Lorenza Romani, paediatrician at Bambino Gesù Children’s Hospital in Italy says the approach is crucial:
“Over the last weeks, we understood that detection of the virus and diagnosis of COVID-19 was not enough. We learned that we had to fight, not only against the virus, but also against the body response that seems to be more serious than the virus infection and more challenging to treat. Today, as never in the past, we need to understand not only the difference between a viral or bacterial infection but we need to discover what and how this new virus can trigger in term of inflammatory response. The consortia’s work is essential to answer to all these questions.”
Lorenza Romani, MD, Pediatrician at Bambino Gesù Children’s Hospital, Italy
What’s different about COVID-19?
COVID-19 is a viral illness, but in severe cases, many features are more similar to a bacterial infection. At the core of their work, the 28 partners - 18 of which are active in both PERFORM and DIAMONDS – have been building a data library of identifiable gene signatures of all common infectious and inflammatory diseases. The teams are working towards adding COVID-19 to this library in order to determine a unique gene signature for COVID-19. With immune signatures from more than 5,000 patients with other infectious diseases in the library, the consortia believe they will be able to find a unique gene signature for COVID-19, which is distinct from other infections. The good news is, work is already underway.
Pablo Rojo who is a Paediatric Infectious Diseases Specialist of Hospital 12 de Octubre, in Spain comments that “when we noticed that there was a need to study and characterise the pandemic virus and its immune response, we decided that PERFORM [& DIAMONDS] was a very useful tool. With the already granted ethical committee approval, we started taking samples from the very beginning of the pandemic in Spain.” On top of this work, the consortia are already developing the technology needed for a rapid diagnostic based on the signatures. Recruitment of COVID-19 patients has commenced at clinical sites across Europe and the first gene signature results with diagnostic potential are expected very soon. Prof Maria Tsolia who coordinates the clinical trials for PERFORM and DIAMONDS in Greece at the National and Kapodistrian University of Athens tells us they have been actively recruiting COVID 19 patients in PERFORM and will soon start to recruit for DIAMONDS. On top of this work, Prof Tsolia has been part of the scientific committee informing the government on nation-wide COVID-19 response and policymaking. She tells us that the low cases and death numbers can be attributed to the early lockdown measures:
“Greece which has a population of about 11 million has had very few cases of COVID 19 (about 2600 cases as of May 4th) and a very low number of deaths (<150) so far. This low number may be attributed to the timely reaction of the Hellenic CDC (EODY) and the Government which has been very much pro-active from the beginning of the pandemic with meticulous containment and mitigation policies. Timely decisions regarding school closure and cancellations of social gatherings, cultural and athletic events before extensive spread of the infection were crucial.”
Prof Maria Tsolia, Professor and Chair of Paediatrics and Paediatric Infectious Diseases at the National and Kapodistrian University of Athens (NKUA), P. and A. Kyriakou Children’s Hospital, Greece.
We are only just learning about the spectrum of illness that COVID-19 can cause. It is already clear that there is a range of severity, and that different sets of symptoms appear to occur in different individuals. Over the last week or so, concerning reports have been emerging in the news of a COVID-19-related inflammatory syndrome developing in children. Just last week, NHS officials said more than 37 children in England have been admitted to hospital with the syndrome, and paediatric experts are investigating what, if any, connection there is with COVID-19. The team believe that the gene signature approach is ideal not only for identifying COVID-19 infection, but also for distinguishing disease subtypes, and potentially understanding this emerging inflammatory syndrome. They have already rapidly activated recruitment of relevant cases. Prof Mike Levin, PERFORM and DIAMONDS lead coordinator and chair of Paediatrics & International Child Health at Imperial College says DIAMONDS will be vehicle for this research across Europe, “DIAMONDS as a study focussed on identifying the molecular differences between infectious and inflammatory diseases, is ideally placed to contribute to the international effort to understand how COVID19 differs from other infections, and how it might be triggering a new syndrome”. The consortia are providing further updates on this developing component on the DIAMONDS website.
It is still early days and emerging developments and information still need to be verified but both PERFORM and DIAMONDS consortia are optimistic that their approach and expertise will lead to make a major contribution to the international efforts against COVID-19.
More in the news on PERFORM AND DIAMONDS and the research into COVID-19 and emerging children syndrome:
Science Mag Doctors race to understand inflammatory condition in kids
The Guardian Doctors raise hopes of blood test for children with coronavirus-linked syndrome
NBC News Blood markers discovered for COVID-linked syndrome in children
Written by Siobhan Markus, Dr Aubrey Cunnington, and Dr Myrsini Kaforou