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Case study: An NIHR Clinician Scientist’s journey to understand COVID-19

NIHR Clinician Scientist Awards have now been replaced by NIHR Advanced Fellowships. The NIHR Fellowship Programme supports individuals on their trajectory to becoming future leaders in NIHR research.

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Intensive care expertise

Before COVID-19, Manu Shankar-Hari’s research focused on how to improve outcomes in sepsis patients and in sepsis survivors. His NIHR Clinician Scientist Award provides five years of postdoctoral support to develop a substantial piece of research in a combined clinical academic role. As well as supporting Manu’s development as a research leader, his Award funds the VACIRiSS Trial and the data science work exploring outcomes in sepsis survivors. The trial is testing whether vaccinating sepsis survivors could improve their immune system, resulting in better long-term outcomes.
 
When the pandemic hit London all of Manu’s primary research was paused, which included the VACIRiSS Trial, and his clinical commitment increased.
 
“My immunobiology expertise was really useful in this context of a new viral pandemic.”

Adjusted focus: COVID-19 research

From the very start of the pandemic, Manu has used his skill and experience in intensive care medicine and translational immunology research in multiple ways in order to understand more about COVID-19 and how to improve outcomes for patients.
 
  • REMAP-CAP Due to research expertise in immunology and sepsis trials, Manu was invited to join a UK Consortium led by NHS Blood and Transplant, to design a randomised clinical trial on the effect of convalescent plasma on critically ill adults with COVID-19. In addition, Manu was asked to coordinate and lead the translational immunology of convalescent plasma therapy in this population. Therefore, he is now co-leading the convalescent plasma treatment trial as part of the REMAP-CAP trial. This international trial is testing a range of treatments for people with COVID-19 and has been given Urgent Public Health (UPH) status.
 
  • ILIAD-7 Manu also successfully submitted a commercially funded UPH proposal for the ILIAD-7 trial, as the UK Chief Investigator. The ILIAD -7 trial is testing whether an agent medicine called human recombinant interleukin-7 [IL-7] is able to boost the immune system’s ability to fight coronavirus infection, by increasing the numbers and function of particular white blood cells (called T lymphocytes). The UK was the first country to start recruitment and recruited the first patient into this intervention.
 
  • COVID-IP Manu’s translational research group focussed their efforts on understanding the immune responses in patients hospitalised with COVID-19 illness. To this end, they secured some local funding and collaborated with another research group within KCL to develop a project that involved understanding how white blood cells change in COVID-19 illness, at pace. The COVID-IP project produced a landmark paper on the immunology of adult COVID-19 illness, published in Nature Medicine. It reports the signature traits of white blood cell changes and highlights an immune signature that predicts the risk of severe illness in adults. These findings have been replicated by other studies.
 
  • PIMS-TS Whilst the pandemic was ongoing, Evelina London Children’s Hospital reported a unique syndrome in children resulting in critical illness. Manu’s research group was one of the first groups internationally to report the immune cell changes in this severe illness referred to as PIMS-TS. This resulted in another landmark paper, published in Nature Medicine, which provided immunological evidence that PIMS-TS is an illness distinct from Kawasaki Disease. This has informed clinical care.
 
Manu’s breadth of work meant he was asked to present evidence during a House of Lords Science and Technology Committee on how an immune response influences the severity and outcome of a COVID-19 illness.

Effect on sepsis research and future career

The pandemic has meant that the VACIRiSS Trial that Manu was conducting as part of the Clinician Scientist Award will be delayed. However, the internal pilot phase report and focus groups were completed during the pandemic. The Data Safety and Monitoring Board has recommended continuation of the trial based on the data thus far. It was also possible to complete the data science work during the pandemic and finalise an online tool that accurately predicts outcomes for sepsis survivors
“Overall, the pandemic has reinforced the value of the unique research skill-set I have got and given me belief in continuing to strive on excellence with my approach to translational research.”
It is perhaps inevitable that the pandemic will change Manu’s future research career, although he hopes that his work during the pandemic will have a positive impact on his career. In the short-term there will be a delay with his planned activities around his sepsis research, but the long-term is still difficult to predict.