ObjectivesMonitoring of SARS-CoV-2 spread and vaccination strategies have relied on antibody (Ab) status as a correlate of protection. We used QuantiFERON™ (QFN) and Activation-Induced Marker (AIM) assays to measure memory T-cell reactivity in unvaccinated individuals with prior documented symptomatic infection (late convalescents) and fully vaccinated asymptomatic donors (vaccinees).MethodsTwenty-two convalescents and 13 vaccinees were enrolled. Serum anti-SARS-CoV-2 S1 and N Abs were measured using chemiluminescent immunoassays. QFN was performed following instructions and interferon-gamma (IFN-γ) measured by ELISA. AIM was performed on aliquots of antigen-stimulated samples from QFN tubes. SARS-CoV-2-specific memory CD4+CD25+CD134+, CD4+CD69+CD137+and CD8+CD69+CD137+T-cell frequencies were measured by flow cytometry.ResultsIn convalescents, substantial agreement was observed between QFN and AIM assays. IFN-γ concentrations and AIM+(CD69+CD137+) CD4+T-cell frequencies correlated with each other, with Ab levels and AIM+CD8+T-cell frequencies, whereas AIM+(CD25+CD134+) CD4+T-cell frequencies correlated with age. AIM+CD4+T-cell frequencies increased with time since infection, whereas AIM+CD8+T-cell expansion was greater after recent reinfection. QFN-reactivity and anti-S1 titers were lower, whereas anti-N titers were higher, and no statistical difference in AIM-reactivity and Ab positivity emerged compared to vaccinees.ConclusionsAlbeit on a limited sample size, we confirm that coordinated, cellular and humoral responses are detectable in convalescents up to 2 years after prior infection. Combining QFN with AIM may enhance detection of naturally acquired memory responses and help stratify virus-exposed individuals in T helper 1-type (TH1)-reactive (QFNposAIMposAbshigh), non-TH1-reactive (QFNnegAIMposAbshigh/low), and pauci-reactive (QFNnegAIMnegAbslow).