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3D rendering of T cell © Blausen Medical

An analysis of blood samples from COVID-19 patients has found that patients with elevated levels of a marker for T cells activity went on to develop only mild symptoms. The study, led by Professor Tao Dong, found that patients with lower levels of this marker had more severe symptoms.

T cells are a core part of the body’s adaptive immune response, producing a tailored response to specific antigens. Measuring key biomarkers when patients first get ill might not only predict who will go on to develop mild versus severe illness, but interventions to change these markers might also help prevent severe illness.

Professor Dong, who is also the co-director of the Oxford University’s, Chinese Academy of Medical Science’s Oxford Institute, analysed data from 71 COVID-19 positive patients hospitalised at Beijing’s You’an Hospital in January and March this year.  53 of the patients turned out to have a mild illness, while 18 had more serious symptoms.

The close collaboration with researchers in China meant that the Oxford team had access to patient blood samples collected at different time points: when the patients were first admitted to hospital (typically a week after first developing symptoms), and then every week for four weeks.

The researchers measured levels of a constellation of small proteins, known as cytokines and chemokines, known to be important for the body’s immune function.

As expected, they found that many markers of inflammation were elevated in patients whose symptoms went on to get worse, as their bodies mobilised their immune system to fight the virus.

But the researchers were surprised to find that levels of one particular chemokine, known as RANTES or CCL5, followed the reverse pattern: compared to healthy people, levels of this cytokine were higher in patients who went on to only have mild symptoms, and lower in patients who continued to get worse.

“It was really surprising to find something the other way around, and yet so clear,” said Professor Dong.

Activating an adaptive response

RANTES specifically helps the immune system’s T cells hone in and destroy infected cells. T cells are powerful: unlike a lot of the body’s other immune responses, which are similar for all kinds of infections, T cells are the core of an adaptive system that tailors the body’s immune response to each specific infections.

Professor Dong thinks that being able to produce this tailored response is what enables some people to fight off COVID-19 more successfully: “I think the higher RANTES levels in patients who recover better is likely to just an indicator of a more successful T cell response, which guides the immune system towards a more adaptive, antigen-specific mode.”

The researchers think that the higher RANTES levels in the patients who go on to develop only mild symptoms are being produced by a group of T cells known as the CD8 T cells: these cells can kill virus-infected cells, including those infected by HIV.

Professor Dong and her collaborators are now studying these processes in the lab, to understand the complex sequence of events that might distinguish an immune response that successfully fights off the novel coronavirus, versus one that makes things worse.

Cytokine storms

One of the ways that the body’s immune response might make things worse is through a cytokine storm: a large release of cytokines that sets of too much inflammation as more and more immune cells respond to the cytokines call.

It’s an attractive idea, and it might explain some otherwise mysterious things about COVID-19: children produce lower levels of inflammation-producing cytokines, and this may explain why they have mild or no symptoms.

But the results from this study suggest that a classical cytokine storm may not be the only cause of a severe COVID19 illness – the researchers found some cytokines associated with a ‘storm’ were raised only in the later stages of the illness, with others were no different in those with mild versus severe illness.

The T Cell response is key

Professor Dong now plans to study the immune response in single cells and tissues as they fight off a novel coronavirus infection.

 

This kind of observational study is important to show us what kind of things we should be looking at. But I’m a T-cell biologist, and we now need to carry out an in-depth analysis of T cells that we’ve isolated from these patients, to find out what exactly what happens to these cells at every stage of the infection.
- Professor Tao Dong

The study is available on the Lancet preprint server.