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-? 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-? 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-? 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-?/IL-2 responses than those whose outcome was death (p<0.05). In addition, IgG response showed significant moderate correlations with IFN-? 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-? responses are fundamental during the acute phase of the disease, while IL-2 is predominant after infection or vaccination. IFN-?/IL-2dual detection is promising for characterizing and assessing the immunization status, and helping in the patient management. IgG response is significantly correlated with both IFN-? and IL-2T-cell responses.