13/11/2020
Key points:
A team of immunology experts from research organisations in Belgium and the UK have come together to apply their pioneering research methods to put individuals鈥 COVID-19 response under the microscope. Published today in the journal Clinical and Translational Immunology, their research adds to the developing picture of the immune system response and our understanding of the immunological features associated with the development of severe and life-threatening disease following COVID-19. This understanding is crucial to guide the development of effective healthcare and 鈥榚arly-warning鈥 systems to identify and treat those at risk of a severe response.
One of the most puzzling questions about the global COVID-19 pandemic is why individuals show such a diverse response. Some people don鈥檛 show any symptoms, termed 鈥榮ilent spreaders鈥, whereas some COVID-19 patients require intensive care support as their immune response becomes extreme. Age and underlying health conditions are known to increase the risk of a severe response but the underlying reasons for the hyperactive immune response seen in some individuals is unexplained, although likely to be due to many factors contributing together.
To investigate the immune system variations that might explain the spectrum of responses, teams of researchers from the VIB Centre for Brain and Disease Research and KU Leuven in Belgium and the 海角社区论坛 in the UK worked with members of the CONTAGIOUS consortium to compare the immune system response to COVID-19 in patients showing mild-moderate or severe effects, using healthy individuals as a control group.
Professor Adrian Liston, senior group leader at the 海角社区论坛 in the UK, explains: 鈥淥ne of our main motivations for undertaking this research was to understand the complexities of the immune system response occurring in COVID-19 and identify what the hallmarks of severe illness are. We believe that the open sharing of data is key to beating this challenge and so established this data set to allow others to probe and analyse the data independently.鈥
The researchers specifically looked at the presence of T cells 鈥 immune cells with a diverse set of functions depending on their sub-type, with 鈥榗ytotoxic鈥 T cells able to kill virus-infected cells directly, while other 鈥榟elper鈥 T cell types modulate the action of other immune cells. The researchers used flow cytometry to separate out the cells of interest from the participants鈥 blood, based on T cell identification markers, cell activation markers and cytokine cell signalling molecules.
Surprisingly, the T cell response in the blood of COVID-19 patients classified as severe showed few differences when compared to healthy volunteers. This is in contrast to what would usually be seen after a viral infection, such as the 鈥榝lu. However, the researchers identified an increase in T cells producing a suppressor of cell inflammation called interleukin 10 (IL-10). IL-10 production is a hallmark of activated regulatory T cells present in tissues such as the lungs. While rare in healthy individuals, the researchers were able to detect a large increase in the number of these cells in severe COVID-19 patients.
Potentially, monitoring the level of IL-10 could provide a warning light of disease progression, but the researchers state that larger-scale studies are required to confirm these findings.
鈥淲e鈥檝e made progress in identifying the differences between a helpful and a harmful immune response in COVID-19 patients. The way forward requires an expanded study, looking at much larger numbers of patients, and also a longitudinal study, following up patients after illness. This work is already underway, and the data will be available within months,鈥 says , at the KU Leuven in Belgium.
鈥淭his is part of an unprecedented push to understand the immunology of COVID-19鈥, concludes Professor Liston. 鈥淥ur understanding of the immunology of this infection has progressed faster than for any other virus in human history 鈥 and it is making a real difference in treatment. Clinical strategies, such as switching to dexamethasone, have arisen from a better understanding of the immune pathology of the virus, and survival rates are increasing because of it鈥.
Publication reference Neumann, J., Prezzemolo, T., Vanderbeke, L. & Roca, C.P. et al. Increased IL-10-producing regulatory T cells are characteristic of severe cases of COVID-19. Clinical and Translational Immunology.
Data availability The research data is openly available at: . The study involved 6 healthy individuals, 23 mild-to-moderate COVID-19 patients (WHO score 3-4) and 20 severe COVID-19 patients (WHO score 5-7).
Press contact Dr Louisa Wood, 海角社区论坛 Communications Manager, louisa.wood@babraham.ac.uk, 01223 496230.
Image description Data plot showing T cells in the blood. Regulatory T cells prevent and repair the damage following an immune response. There are many different types of regulatory T cells with each type using different proteins to suppress pathology. This graph visualises regulatory T cell in the blood samples analysed as a single dot, with the different colours indicating the different types of regulatory T cells. Image: Carlos Roca and Julika Neumann.
Affiliated authors (in author order): Dr Carlos Roca, postdoctoral researcher, Liston lab Dr Oliver Burton, senior postdoctoral researcher, Liston lab Prof Adrian Liston, senior group leader, Immunology research programme
Research funding This work was supported by the VIB Grand Challenges Program, the KUL C1 program, the FWO Hercules program, a European Union Horizon 2020 research and innovation programme to Adrian Liston (grant agreement No 779295), and funding from the Biotechnology and Biological Sciences Research Council through Institute Strategic Program Grant funding and a Core Capability Grant to the 海角社区论坛.
Additional/related resources: News, 14th October 2020 Call to arms - processing patient samples at the COVID-10 Biocentre News, 28th September 2020 Volunteer account from the COVID-19 testing centre News, 22nd July 2020 New role for white blood cells in the developing brain News, 6th May 2020 The 海角社区论坛鈥檚 contribution to the COVID-19 response
About the 海角社区论坛 The 海角社区论坛 undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. 海角社区论坛 focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.
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13 November 2020