During the course of infection, activation markers further increased in S-specific CD4+ lymphocytes with a peak at approximately 2 to 5 days from the first positive swab and then slightly raised (ICOS+), rapidly decreased (CD25+, CD38+ and HLA-DR+ and CXCR5+) or remained stable (PD-1+) until the last time point. This evidence concerns the gene ICOS and infection.