The good news on Covid-19 just keeps coming. The first evidence backing a link between coronavirus-reactive T cells with immunity emerged today, and while – as with the results on Pfizer and Biontech’s vaccine yesterday – more work must be done, this is a positive sign.
The data come from a prospective cohort of the UK-based Edsab-Home trial, which is evaluating a range of Covid-19 assays. Specifically the readout concerns Oxford Immunotec’s T-Spot Discovery test, and with the UK group lining up regulatory submissions this assay could become a useful tool in the fight against the virus.
The Edsab-Home trial is a collaboration between several testing companies and Public Health England. This particular cut of the data was released as a preprint ahead of peer review.
Spot the difference
Starting in June 2020, 2,826 people working in hospitals or in the fire and police services in England – high-risk occupations during the pandemic – were enrolled into Edsab-Home and allocated to the cohort testing Oxford Immunotec's assay.
Subjects’ baseline levels of interferon-γ secreting, Sars-Cov-2-responsive T cells were assessed using the company's T-Spot kit, which uses the company’s EliSpot technology. Enrolees were also tested for antibodies to the coronavirus using either Roche’s Elecsys anti-Sars-Cov-2 test or Euroimmun’s anti-S IgG immunoassay.
The participants were followed until mid-October, a median of 118 days. In that period none of the participants with high levels of T cells responsive to the coronavirus’s spike, nuclear and membrane (SNM) proteins developed symptomatic Covid-19 infection, whereas among those with low T-cell responses there were 20 confirmed infections. All 20 infections occurred in people who were also seronegative; that is, they did not have detectable levels of antibodies against the coronavirus.
Statistically, Covid-19 was significantly more common in individuals with lower T-Spot SNM results over the time period studied, at p=0.001 and log-rank p=0.007. This is the first evidence that high levels of coronavirus-responsive T cells are associated with protection from symptomatic infection, Oxford Immunotec claimed.
Of the volunteers recruited irrespective of previous Covid-19 PCR test results, around a quarter had elevated levels of SNM-responsive T cells. Of these, just over half were seropositive for Covid-19 antibodies. Among seronegative individuals – those without detectable antibodies to the virus – the subjects with lower numbers of SNM-responsive T cells were also more likely to develop Covid-19, but the difference was on the border of significance, at p=0.046 and log-rank p=0.08.
The researchers said that the protective association of high T-Spot SNM results in the seronegative population raised the question of whether seropositivity might appear protective in part because high antibody levels are associated with high coronavirus-responsive T-cell numbers.
Finding out how strongly T-cell responses correlate with antibody production was one of the aims of Edsab-Home, as Oxford Immunotec’s chief executive Peter Wrighton-Smith told Evaluate Vantage last month (The other kind of Covid-19 immunity, October 7, 2020).
Since in this trial the T-Spot test detected PCR-confirmed Covid-19 infections that were not positive in antibody testing, Oxford Immunotec says antibody testing alone might underestimate the working age population at lower risk of reinfection.
However, this finding does not necessarily mean that testing for reactive T cells is more accurate than antibody testing when it comes to identifying individuals who have been exposed to Covid-19. The researchers wrote that seronegative people with reactive T cells had could have had their cells primed by the virus that causes the common cold. Still, a scenario whereby the T cells were primed by minimally symptomatic Sars-Cov-2 infection, without antibody generation, cannot be excluded.
A four-month long study in fewer than 3,000 people in a single country cannot be regarded as conclusive proof that the presence of coronavirus-reactive T cells confers immunity to Covid-19. But the data certainly do not disprove that hypothesis. If the findings are not contradicted by future research, T-cell testing could become a major part of efforts to control the pandemic – and Oxford Immunotec could be in the vanguard.