Immune driven evolution of SARS-CoV-2 within and across hosts

Observing the role of the immune system in the evolution of emerging pathogens can provide rare windows into both virus evolution and indicate therapeutic vulnerabilities. We study the between host evolution of dinucleotide motifs in emerging SARS-CoV-2 strains for evidence of whether pressure to avoid presentation of CpG dinulceotides was a factor in either host transmission or early adaptation. We model the problem as a competition between selective and entropic forces as we had previously done for influenza and other RNA viruses. Moreover, there is increasing evidence that T Cell responses are both a critical factor in vaccine response and severe COVID. To study this in a controlled manner we look at the relationship between SARS-CoV-2 evolution, T cell evolution and COVID severity in a cohort of patients with impaired B Cell responses. We find that while the T cell machinery is a critical determinant of outcomes in these cases.