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

Abstract

Background We measured T-cell and antibody responses to SARS-CoV-2 in vaccinated patients hospitalized for COVID-19, and explored their potential value to predict outcomes. Methods 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-γ release assay (IGRA). Primary outcome was all-cause 28-day mortality or need for ICU admission. Cox models were used to assess associations with outcomes. Results 158 (87.3%) of 181 individuals 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 needed ICU were less likely to have both unspecific and specific T-cell responses in IGRA. In adjusted analyses, for the entire cohort, having both T-cell and antibody responses at admission (aHR:0.16; 95%CI, 0.05-0.58) and Omicron variant (aHR:0.38; 95%CI, 0.17-0.87) reduced the hazard of 28-day mortality or ICU, whereas higher Charlson comorbidity index (aHR:1.27; 95%CI, 1.07-1.51) and lower SpO2/FIO2 (aHR:2.36; 95%CI, 1.51-3.67) increased the risk. Conclusions Pre-existing 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.

Integrating SARS-CoV-2-specific interferon-γ release assay testing in the evaluation of patients hospitalized with COVID-19

“…SARS-CoV-2 IGRA results were found to be associated with patient outcomes, as we have seen in a preliminary analysis conducted in the vaccinated patient group ( 9 ). SARS-CoV-2 IGRA-negative persons exhibited higher mortality rates, irrespective of age, comorbidity burden, initial severity, and the antibody response.…”

“…Whole blood from lithium heparin tube was used for IGRA incubation within 4 h. SARS-CoV-2 cellular response was measured on the first day of admission using a specific quantitative IFN-γ release assay according to the manufacturer’s instructions (Quan-T-Cell SARS-CoV-2, Euroimmun, Germany). Details are provided elsewhere ( 9 , 17 ). Briefly, lithium-heparinized blood from each patient was incubated for 21 h at 37°C in the three tubes supplied: blank tube (unstimulated) for the individual IFN-γ background and mitogen tube for non-specific IFN-γ secretion as controls and stimulation tube coated with antigens of the SARS-CoV-2 spike protein for specific IFN-γ secretion.…”

“…Emerging data suggest a prominent role for T cells in protection against severe disease. Mild disease is characterized by an early T cell response ( 2 , 7 , 8 ), while insufficient or exhausted T cell responses are associated with severe COVID-19, even in vaccinated patients ( 9 – 11 ). Assessment of the magnitude and determinants of T cell responses in patients with acute severe COVID-19 may help adopting targeted preventive and therapeutic measures.…”

COVID-19 point-of-care tests can identify low-antibody individuals: In-depth immunoanalysis of boosting benefits in a healthy cohort

“…Cellular immune responses are known to reduce symptomatic and severe disease ( 69 ) against SARS-CoV-2 infection in the setting of waning and sub-optimal neutralizing Ab titers ( 58 ); protection against hospitalization and death among individuals experiencing a breakthrough infection with a SARS-CoV-2 variant is high ( 70 ), suggesting that T cells play a substantial role against severe disease in the context of infection by SARS-CoV-2 variants ( 71 ). In our cohort of healthy adults, T cell clonal levels of TCR breadth and depth followed a typical trend reflective of healthy T cell response ( 38 ), and there were no notable differences among LFA-positive and LFA-negative individuals at any sampling point.…”