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A team of researchers from La Jolla Institute for Immunology (LJI), The University of Liverpool, and the University of Southampton, suggests that people with severe COVID-19 cases may be left with more of the protective ‘memory’ T cells needed to fight reinfection.
The research, published in Science Immunology, is the first to describe the T cells that fight coronavirus in detail.
T-cells are a type of white blood cell that is of vital importance to the immune system and is at the core of adaptive immunity, the system that helps tailor the body’s immune response to specific diseases.
Scientists at LJI have investigated which antibodies and T cells are important for fighting the coronavirus since the start of the COVID-19 pandemic. As experts in genomics the study co-leaders, Professor Pandurangan Vijayanand from LJI and Christian Ottensmeier, Professor of Immuno-Oncology at the University of Liverpool, Consultant Medical Oncologist at The Clatterbridge Cancer Centre and adjunct professor at LJI, have used sequencing tools to uncover which T cell subsets may control disease severity. For this study, they used a technique called ‘single-cell transcriptomics analysis’ to study the expression of individual genes of more than 80,000 CD8+ T cells isolated from both COVID-19 patients and non-exposed donors.
The researchers studied CD8+ T cells from 39 COVID-19 patients and 10 subjects who had never been exposed to the virus, and found that of the COVID-19 patients, 17 patients had a milder case that did not require hospitalisation, 13 had been hospitalised, and nine had needed additional ICU support.
Weaker CD8+ T cell responses were found in in patients with milder COVID-19 cases and the strongest CD8+ T cell responses in the severely ill patients who required hospitalisation or ICU support.
The researchers found that signs of T cell ‘exhaustion’, when cells receive so much immune system stimulation during a viral attack that they are less effective in doing their jobs, were identified in milder cases. As such, the researchers have stated it is worth studying whether T cell exhaustion in these types of cases may hinder a person’s ability to build long-term immunity to COVID-19.
Professor Pandurangan Vijayanand, said: “The data from this study suggest people with severe COVID-19 cases may have stronger long-term immunity. People who have severe disease are likely to end up with a good number of memory cells. People with milder disease have memory cells, but they seem exhausted and dysfunctional—so they might not be effective for long enough. This research highlights the power of these new tools to understand human immunology”
Professor Ottensmeier, said: “This study highlights the enormous variability in how human beings react to a viral challenge. There is an inverse link between how poorly T cells work and how bad the infection is. I think that was quite unexpected. This study is very much a first step in understanding the spectrum of immune responses against infectious agents.”
Moving forward, the researchers hope to use single-cell sequencing techniques to look at CD8+ T cells in cancer patients with COVID-19 infection.
The full study, entitled ‘Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells’, can be found here.
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