Functional and dysfunctional human CD4 T cell and B cell responses to bacteria and viruses

PROJECT SUMMARY Pre-existing T cell memory to SARS-CoV-2 is detectable in ~50% of people. We first reported this, and we have since shown that this may largely be due to crossreactive memory CD4+ T cells from common cold coronavirus (CCC) infections. While this observation has been reproduced on three continents, the big unanswered question is whether these crossreactive memory T cells (i) confer some form of protection against COVID-19 disease severity, (ii) have no impact on COVID-19 severity, or (iii) increase COVID-19 disease severity. This issue has been widely discussed in scientific, public, and political spheres, and it potentially has major ramifications for understanding the COVID-19 pandemic. The direct experiment to address this topic is a longitudinal study of uninfected individuals at risk for acquisition of SARS-CoV-2, then assessing COVID-19 disease severity in individuals who contract SARS-CoV-2 infection, stratified between individuals who did or did not have pre- existing T cell memory to SARS-CoV-2.