T-Cell Immunity Against Severe Acute Respiratory Syndrome Coronavirus 2 Measured by an Interferon-γ Release Assay Is Strongly Associated With Patient Outcomes in Vaccinated Persons Hospitalized With Delta or Omicron Variants

Background We measured T-cell and antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vaccinated patients hospitalized for coronavirus disease 2019 (COVID-19) and explored their potential value to predict outcomes. Methods This was a prospective, longitudinal study including vaccinated patients hospitalized with Delta and Omicron SARS-CoV-2 variants. TrimericS-IgG antibodies and SARS-CoV-2 T-cell response were measured using a specific quantitative interferon-& gamma; release assay (IGRA). Primary outcome was all-cause 28-day mortality or need for intensive care unit (ICU) admission. Cox models were used to assess associations with outcomes. Results Of 181 individuals, 158 (87.3%) had detectable SARS-CoV-2 antibodies, 92 (50.8%) showed SARS-CoV-2-specific T-cell responses, and 87 (48.1%) had both responses. Patients who died within 28 days or were admitted to ICU were less likely to have both unspecific and specific T-cell responses in IGRA. In adjusted analyses (adjusted hazard ratio [95% confidence interval]), for the entire cohort, having both T-cell and antibody responses at admission (0.16 [.05-.58]) and Omicron variant (0.38 [.17-.87]) reduced the hazard of 28-day mortality or ICU admission, whereas higher Charlson comorbidity index score (1.27 [1.07-1.51]) and lower oxygen saturation to fraction of inspired oxygen ratio (2.36 [1.51-3.67]) increased the risk. Conclusions Preexisting immunity against SARS-CoV-2 is strongly associated with patient outcomes in vaccinated individuals requiring hospital admission for COVID-19. Persons showing both T-cell and antibody responses have the lowest risk of severe outcomes. In this prospective study of vaccinated patients hospitalized for COVID-19, T-cell immunity against SARS-CoV-2 measured by interferon-& gamma; release assay (IGRA) was strongly associated with patient outcomes. Persons showing both positive antibody test and T-cell responses by IGRA had the lowest risk of mortality.