T-Cell Tests Unreliable in Establishing Previous COVID-19 Infection, Finds New Study

T-cell tests can be unreliable in establishing previous COVID-19 infection, according to the findings of a new study.

In the study, scientists at Uppsala University (Uppsala, Sweden) and Karolinska Institutet (Stockholm, Sweden) jointly analyzed if T-cell tests can be used to determine whether people have had COVID-19. By analyzing the T cells’ responses to varying peptide compositions, the researchers were able to see that different peptide pools produced divergent responses, and that a risk of false-positive responses existed. In the scientists’ view, this risk is due to the fact that the peptides can give rise to responses from memory T cells that originated in some way other than through a SARS-CoV-2 infection – from a common cold, for example.

When the scientists attempted to avoid using peptides that might give rise to these cross-reactive responses, there was an increase in the specificity of the test – that is, its ability to establish genuine negative responses – but its sensitivity (ability to detect a true positive response) simultaneously declined at the time of sampling and analysis, which was 4-5 months post COVID-19.

“In the follow-up study, the participants with a relatively mild initial disease clearly didn’t always have measurable SARS-CoV-2 specific T cells in blood. But among those with a disease that’s initially more serious, there were more who had measurable SARS-CoV-2-specific T cells in blood over time,” said Sara Mangsbo, a research scientist in immuno-oncology at Uppsala University. “The correlation we found between the severity of the disease and a measurable, established memory response in the blood isn’t entirely unexpected; but it’s still important to establish, since the use of T-cell tests has been a matter of public discussion for numerous reasons."

“It’s also important to say that the subjects’ blood doesn’t always contain the memory T cells after the disease is over. Still, cells in tissues – which aren’t measurable by means of a blood-based test for T cells – may have a part to play in how ill people get during an infection,” said Charlotte Thålin, a specialist doctor and researcher responsible for the COMMUNITY study at Danderyd Hospital and Karolinska Institutet. “T-cell tests will continue to have an important part to play in research and studies, but probably a smaller one in diagnostics and at individual level for SARS-CoV-2 in particular.”

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Uppsala University
Karolinska Institutet