Here, for one, is a multi-institute study from the UK. The authors are looking at 100 COVID-19 patients over a six-month period and correlating the antibody and T-cell responses. What they see is what you’d want to see: the T-cell responses appear to be durable over that time. They do seem to be correlated with the severity of the infection – responses were definitely higher in the people who had experienced symptoms, as opposed to asymptomatic cases. The T-cell response against the coronavirus nucleoproteins seemed to correlate with the degree of later decline of the antibody response to those proteins, but this did not hold true for the response to the Spike protein (the two were uncorrelated – antibody responses to the Spike protein could go down, while T-cell responses remained). 80% of the patients who had mild-to-moderate infection, however, did have Spike-specific cellular responses at the six month time point. For T-cell aficionados, the response was mostly (about 2:1) CD4+ cells with IL-2 cytokine expression, as opposed to CD8+ cells. Both types showed both Spike-directed and non-Spike-protein-directed responses, but the CD8+ were more biased towards the various non-Spike proteins.
Overall, this work suggests that people who have experienced at least some degree of symptomatic infection should have reasonably long-lasting T-cell responses. There does seem to be a “set point” for these, correlating with that severity. What will tie this to the vaccine efforts will be the data on the T-cell responses induced by the vaccines themselves (which as of now are completely directed towards a Spike protein response), as compared to the wild-type viral infection. And I presume that we’ll be getting those numbers from the ongoing trials.
Now here’s another new preprint from a different multicenter UK team that has some really interesting correlations. It’s a prospective study looking at 2,826 front-line workers there – they’ve been measuring their T-cell levels (using a new assay from Oxford Immunotec) and their antibody profiles since June and seeing who comes down with coronavirus infection over time. All the workers who were seropositive at the start (displaying antibodies against coronavirus proteins) also had robust T-cell response levels. In the seronegative group, there were some with robust T-cell numbers and some without. Split up another way, of the people in the study with strong T-cell responses to the coronavirus proteins, only about 55% of them had detectable antibodies to those proteins. Over time, 20 of the overall weak-T-cell group were infected with the virus, while zero of the strong T cell response group were (p = 0.006).
That suggests that there may indeed be some protective T-cell immunity out there that is being missed by a focus on antibody levels (as has been suspected), but it also says that you can’t just extrapolate this to the whole population by any means: we don’t all have T-cells ready to go. But if you do, you may have a substantial amount of protection, and this might be detectable by a relatively simple assay.
That last point has been the holdup in this area: the story has been all about antibodies because the assays for those are far, far easier to set up. T cell assays are very labor intensive indeed, and the sample sizes in the papers on them tend to be in the dozens. But as you can see, the Oxford Immunotec people are trying to improve that, and so is a company called Adapative Technologies here in the US (and there are others). They have a big write-up in the New York Times this week, and it’s a good article. A quote from an immunologist in it sums things up well: “There has. . .never been great demand for wading into the intricacies of T cell tests.” Adaptive’s recent work on a population in Italy suggests that its test is definitely better at determining whether a person has had a previous coronavirus infection (as opposed to antibody measurements), and if we put that together with the other papers mentioned, it could be that this extends to saying how much protection these people retain.
So the story is coming together. And just as vaccine work is never going to be the same after the huge amounts of work during this pandemic, it looks like T-cell research is never going to be the same, either. They’re both going to be better, faster, and more detailed, and that’s good. Because we’re going to need all this again some day.
