Whole blood-based measurement of SARS-CoV-2-specific T cells reveals asymptomatic infection and vaccine immunogenicity in healthy subjects and patients with solid organ cancers

Accurate assessment of SARS-CoV-2 immunity is critical to evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T cell responses are a critical feature that will likely form a key correlate of protection against COVID-19. Here, we developed and optimised a high-throughput whole blood-based assay to determine the T cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 231 healthy donors and 68 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were analysed for TH 1-type cytokines. Highly significant differential IFN-γ+ /IL-2+ SARS-CoV-2-specific T cell responses were seen amongst previously infected COVID-19-positive healthy donors in comparison to unknown / naive individuals (P<0.0001). IFN-γ production was more effective at identifying asymptomatic donors, demonstrating higher sensitivity (96.0% vs. 83.3%) but lower specificity (84.4% vs. 92.5%) than measurement of IL-2. A single COVID-19 vaccine dose induced IFN-γ and/or IL-2 SARS-CoV-2-specific T cell responses in 116/128 (90.6%) of healthy donors, reducing significantly to 27/56 (48.2%) when measured in cancer patients (P<0.0001). A second dose was sufficient to boost T cell responses in the majority (90.6%) of cancer patients, albeit IFN-γ+ responses were still significantly lower overall than those induced in healthy donors (P=0.034). Three-month post-vaccination T cell responses also declined at a faster rate in cancer patients. Overall, this cost-effective standardisable test ensures accurate and comparable assessments of SARS-CoV-2-specific T cell responses amenable to widespread population immunity testing, and identifies individuals at greater need of booster vaccinations.