Chandelier
Senior Member (Voting Rights)
Immune dysregulation in prolonged Long-COVID: lymphocytes emerge as key mediators of persistent inflammation, exhaustion and cytotoxicity
Despite the widespread prevalence, Long-COVID aetiology remains poorly understood, but emerging evidence points to immune dysregulation as a potential mechanism involved in its development or persistence.
We reconstructed the cell state and intercellular communication using differentially expressed gene profiling and ligand–receptor interaction analyses.
Distinct interferon responses in these cell populations at the acute phase for patients who go on to develop Long-COVID indicate early disease mediator potential.
The observed changes in immune cell subsets at the acute phase of the infection may be predictive of Long-COVID progression and could be useful in understanding disease aetiology while the observed long-term effects are crucial to developing therapeutic and diagnostic tools.
Web | DOI | PDF | Journal of Translational Medicine
Springe, Marta Liva; Vaivode, Kristīne; Saksis, Rihards; Vainšeļbauma, Nineļa Miriama; Ansone, Laura; Brīvība, Monta; Niedra, Helvijs; Rovite, Vita
Abstract
Background
Long-COVID affects at least 10% of COVID-19 survivors, displaying debilitating symptoms across multiple organ systems.Despite the widespread prevalence, Long-COVID aetiology remains poorly understood, but emerging evidence points to immune dysregulation as a potential mechanism involved in its development or persistence.
Methods
This study presents a unique analysis of the peripheral blood mononuclear cell transcriptomic profile of COVID-19 and Long-COVID patients at single-cell resolution.We reconstructed the cell state and intercellular communication using differentially expressed gene profiling and ligand–receptor interaction analyses.
Results
Our results reveal altered T and natural killer 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.Distinct interferon responses in these cell populations at the acute phase for patients who go on to develop Long-COVID indicate early disease mediator potential.
Conclusions
Collectively, these findings provide insight into the immune processes underlying the progression of COVID-19 into a chronic Long-COVID state.The observed changes in immune cell subsets at the acute phase of the infection may be predictive of Long-COVID progression and could be useful in understanding disease aetiology while the observed long-term effects are crucial to developing therapeutic and diagnostic tools.
Web | DOI | PDF | Journal of Translational Medicine