Springe, M. L.; Vaivode, K.; Saksis, R.; Vainselbauma, N. M.; Ansone, L.; Briviba, M.; Niedra, H.; Rovite, V.

Long-COVID affects at least 10% of COVID-19 survivors, displaying debilitating symptoms across multiple organ systems. Despite the increasing prevalence, the underlying causes remain unclear. This study presents a unique analysis of the PBMC transcriptomic landscape of COVID-19 and Long-COVID patients at a single-cell resolution. We reconstructed the cell state and communication using differentially expressed gene profiling and ligand-receptor interaction analyses. Our results reveal altered T and NK cell subset proportions, diminished proliferating lymphocyte and B cell signalling capacity, and the expression of exhaustion and cytotoxicity associated genes 1.5 - 2 years post-infection, suggesting incomplete immune recovery. Collectively, these findings provide insights into the immune processes underlying the progression of COVID-19 into a chronic Long-COVID state.