Abstract: Compositions and methods are provided for detection, diagnosis and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) and for characterization of SARS-CoV-2 antigen-specific T-cell immune responsiveness in COVID-19 patient samples, including in secondary in vitro immune response assays for long-lived anamnestic (memory) T-cell responses. Disclosed compositions and methods include a method that comprises contacting, in vitro, whole blood samples from subjects suspected of having COVID-19 or who have previously been exposed to SARS-CoV-2, with synthetic peptides comprising T-cell epitope-containing regions derived from SARS-CoV-2 Spike proteins; and indirectly detecting SARS-CoV-2-specific activated T-cells by determining production of a T-cell immune response indicator (e.g., interferon-?) in response to stimulation by the Spike protein-derived peptides.