The appropriate immunosurveillance tools are foundational for the creation of therapeutics, vaccines, and containment strategies when faced with outbreaks of novel pathogens. During the COVID-19 pandemic, there was an urgent need to rapidly assess immune memory following infection or vaccination. Although there have been attempts to standardize cellular assays more broadly, methods for measuring cell-mediated immunity remain variable across studies. Commonly used methods include ELISPOT, intracellular cytokine staining, activation-induced markers, cytokine secretion assays, and peptide–MHC tetramer staining. Although each assay offers unique and complementary information on the T cell response, there are challenges associated with standardizing these assays. The choice of assay can be driven by sample size, the need for high throughput, and the information sought. A combination of approaches may be optimal. This review describes the benefits and limitations of commonly used methods for assessing T cell immunity across SARS-CoV-2 studies.

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