ABSTRACT
The immunological picture of how different patients recover from COVID-19, and how those recovery trajectories are influenced by infection severity, remain unclear. We investigated 140 COVID-19 patients from diagnosis to convalescence using clinical data, viral load assessments, and multi-omic analyses of blood plasma and circulating immune cells. Immune-phenotype dynamics resolved four recovery trajectories. One trajectory signals a return to pre-infection healthy baseline, while the other three are characterized by differing fractions of persistent cytotoxic and proliferative T cells, distinct B cell maturation processes, and memory-like innate immunity. We resolve a small panel of plasma proteins that, when measured at diagnosis, can predict patient survival and recovery-trajectory commitment. Our study offers novel insights into post-acute immunological outcomes of COVID-19 that likely influence long-term adverse sequelae.
ABSTRACT
We report here on antigens from the SARS-CoV-2 virus spike protein, that when presented by Class I MHC, can lead to cytotoxic CD8+ T cell anti-viral responses in COVID-19 patients. We present a method in which the SARS-CoV-2 spike protein is converted into a library of peptide antigen-Major Histocompatibility Complexes (pMHCs) as single chain trimers that contain the peptide antigen, the MHC HLA allele subunit, and the {beta}-2 microglobulin subunit. This library is used to detect the evolution of virus-specific T cell populations in four COVID-19 study participants two of which share one HLA allele, and the other two a second HLA allele, at two time points over the initial course of infection. HLA-matched participants exhibit similar virus-specific T cell populations, but very different time-trajectories of those populations. This strategy can be used to track those virus-specific T cell populations over the course of an infection, thus providing deep insight into the SARS-CoV-2 immune system trajectories observed in different COVID-19 patients.
