September 4, 2020

expert reaction to study looking at T cell responses in people who have had COVID-19

A study, published in Nature Immunology, looked at T cell responses in people who have had COVID-19.

Dr Alison Whitelegg, on behalf of the Association for Clinical Biochemistry and Laboratory Medicine (ACB)’s Immunology Professional Committee, said: 

Is this a robust study, what are it’s strengths and limitations? 

“This is a neat study from eminent T cell immunologists utilising cutting edge technology that has built up over the last couple of decades and that enables us to study viral specific T cell immunity in depth. 

“The study was limited to 42 patients and authors acknowledge that more numbers are needed and further studies to take into account how individuals with different HLA (tissue types) may differ in response to these T cell epitopes and therefore vaccination.  However, T cell studies require expertise and significance hands-on time, with this in mind the numbers collected and studied are impressive: 

28 mild 

14 severe 

16 unexposed – the availability of frozen stored PBMCs stored pre pandemic was a great resource in this study. 

“There was no significant differences in age or gender – this will be important to look at to see how T cell responses change in the older generation (we know they decline). 

Does the press release accurately reflect the study? 

“Yes. 

What does this tell us about the T cell immune response in mild versus severe cases? 

“Severe: significantly larger overall T cell response – overactive immune system? 

Mild cases: more CD8+ more varied cytokine ‘flavour’ Individuals with good CD8+ responses seem to do better.  Again, HLA type may be important here. 

How does this compare with what we know about the antibody response? 

“The studies compared antibodies against spike etc. and found T cell responses against spike, NP and NBD.  We can look for T cell memory even when antibody has waned. 

Do we know how long the T cell response might last? 

“Further studies will be needed to demonstrate this but the study uses technology that will be able give us this data in longitudinal studies.  The fact that memory cells are elicited means that these should be long lived in immunocompetent people as has been seen for other viruses. 

Are there any implications for potential treatments or vaccines? 

“Vaccines should incorporate these epitopes and not just be directed at Spike protein. 

Is this good news? 

“Yes.  Need to bear in mind those populations who do not have well-functioning T cells such as the elderly.  Also HLA types – perhaps some people cannot present an immunodominent peptide and this is why some are uniquely susceptible. 

Might some people still have a T cell response who no longer have antibodies; if so what are the implications? 

“Yes, as above, antibodies decline as part of a primary immune response and what is left are a pool of memory B cells and T cells ready to respond to re-exposure to a virus – we hope this would be long-lived but we don’t know yet and need to get data on this.” 

Prof Daniel Altmann, Professor of Immunology, Imperial College London, said: 

“This paper from Oxford offers a very comprehensive and high-tech view of the T cell response to SARS-CoV-2, across the spectrum from mild to severe disease.  It confirms that most who’ve had COVID-19 have a T cell immune response that can recognise many parts of the virus. 

“Papers like this start to supply us with the toolkit we need to describe immunity to the virus.  As such it’s an important study but care should be taken not to misconstrue T cell data as confirming that people have some greater level of herd immunity than assumed from antibody data.” 

Dr Andrew Freedman, Reader in Infectious Diseases, Cardiff University, said: 

“The majority of studies to date of the immune response in those who have had Covid-19 infection have focussed on the presence of antibodies to the virus.  However, it is well recognised that T cell responses are crucially important in both protection against and recovery from viral infections. 

“This high quality study describes in detail the T cell responses found in the blood of patients who have recovered from the infection, demonstrating significant differences between those who had mild and those who had more severe infection.  Such studies are important in furthering our understanding of how the immune system is able to control the virus and may help in the discovery of new ways to treat the infection as well as in the design of novel vaccines.” 

‘Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19’ by Yanchun Peng et al. was published in Nature Immunology on Friday 4 September 2020. 

DOI: 10.1038/s41590-020-0782-6 

https://www.nature.com/articles/s41590-020-0782-6

All our previous output on this subject can be seen at this weblink: 

www.sciencemediacentre.org/tag/covid-19 

Declared interests 

None received.