Heterogeneous immunological recovery trajectories revealed in post-acute COVID-19

Su, Y.; Yuan, D.; Chen, D. G.; Wang, K.; Choi, J.; Dai, C. L.; Hong, S.; Zhang, R.; Xie, J.; Li, S.; Scherler, K.; Pavlovitch-Bedzyk, A.-J.; Dong, S.; Lausted, C.; Ng, R. H.; Lee, I.; Fallen, S.; Kornilov, S. A.; Baloni, P.; Duvvuri, V. R.; Anderson, K. G.; Li, J.; Yang, F.; Rostomily, C.; Troisch, P.; Smith, B.; Zhou, J.; Mackay, S.; Murry, K.; Edmark, R.; Jones, L.; Zhou, Y.; Rowen, L.; Liu, R.; Chour, W.; Berrington, W. R.; Wallick, J. A.; Algren, H. A.; Wrin, T.; Petropoulos, C.; Wei, W.; Price, N. D.; Subramanian, N.; Hadlock, J.; Magis, A. T.; Ribas, A.; Lanier, L. L.; Boyd, S. D.; Blues,

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.