Finally, in individuals with COVID-19, we identified a striking inflammatory-like amplification of SARS-CoV-2 responses with higher BMI and a unique extrafollicular and poorly functioning SARS-CoV-2 repertoire shift toward higher IgM and FcγRIIB binding capacity in those with lower nadir CD4, but we did not see major influences of other host factors on the SARS-CoV-2 repertoire. Here, CD4 is linked to COVID-19.