The measurement of specific T-cell responses can be a useful tool for COVID-19 diagnostics and clinical management. In this study, we evaluated the IFN-γ T-cell response against the main SARS-CoV-2 antigens (spike, nucleocapsid and membrane) in acute and convalescent individuals classified according to severity, and in vaccinated and unvaccinated controls. IgG against spike and nucleocapsid were also measured. Spike antigen triggered the highest number of T-cell responses. Acute patients showed a low percentage of positive responses when compared to convalescent (71.6% vs. 91.7%, respectively), but increased during hospitalization and with severity. Some convalescent patients showed an IFN-γ T-cell response more than 200 days after diagnosis. Only half of the vaccinated individuals displayed an IFN-γ T-cell response after the second dose. IgG response was found in a higher percentage of individuals compared to IFN-γ T-cell responses, and moderate correlations between both responses were seen. However, in some acute COVID-19 patients specific T-cell response was detected, but not IgG production. We found that the chances of an IFN-γ T-cell response against SARS-CoV-2 is low during acute phase, but may increase over time, and that only half of the vaccinated individuals had an IFN-γ T-cell response after the second dose.

Background: The study of specific T-cell responses against SARS-CoV-2 is important for understanding long-term immunity and management of the infection. Aim: To assess specific SARS-CoV-2 IFN-γ and IL-2 responses using a FluoroSPOT assay during acute disease, convalescence, and after vaccination, and compare it to humoral response. Methods: Blood samples were drawn from acute COVID-19 patients (n=66) and convalescent individuals (n=104) classified according to disease severity; and from unvaccinated (n=21) and vaccinated (n=72) uninfected individuals. IFN-γ and IL-2 T-cell responses were measured with a FluoroSPOT assay (GenID, Germany). IgGs against spike (S) and nucleocapsid (N), IgMs against N, and neutralizing antibodies were also analyzed (Euroimmun, Germany). Results: A higher IFN-γ secretion was found in acute patients when compared with IL-2. In contrast, IL-2 was more secreted in convalescent and vaccinated individuals. Severe acute patients under mechanical ventilation displayed significantly higher IFN-γ/IL-2 responses than those whose outcome was death (p<0.05). In addition, IgG response showed significant moderate correlations with IFN-γ T-cell response (SR=0.451, p<0.0001 for S IgGs, and SR=0.397, p<0.0001 for N IgG) and IL-2 T-cell response (SR=0.583, p<0.0001 for S IgG, and SR=0.464, p<0.0001 for N IgG). Conclusions: IFN-γ responses are fundamental during the acute phase of the disease, while IL-2 is predominant after infection or vaccination. IFN-γ/IL-2 dual detection is promising for characterizing and assessing the immunization status, and helping in the patient management. IgG response is significantly correlated with both IFN-γ and IL-2 T-cell responses.