Globally, our results provide advances in knowledge about the specific humoral response during the acute phase of SARS-CoV-2 infection in which (i) specific IgA against the N protein dominate and could be used as a marker to estimate the date of infection, (ii) specific IgG against the S protein is delayed, and their quantity and quality are lower compared to N, and inversely correlated with age, CXCL10 and FasL levels and, finally, and (iii) lower anti-S response is associated with higher levels of CD4 T-cell death. This evidence concerns the gene CD4 and infection.