Cell-specific housekeeping role of lncRNAs in COVID-19-infected and recovered patients.

A plethora of studies have demonstrated the roles of lncRNAs in modulating disease severity and outcomes during infection. However, the spatio-temporal expression of these lncRNAs is poorly understood. In this study, we used single-cell RNA-seq to understand the spatio-temporal expression dynamics of lncRNAs across healthy, SARS-CoV-2-infected, and recovered individuals and their functional role in modulating the disease and recovery. We identified 203 differentially expressed lncRNAs, including cell type-specific ones like MALAT1 , NEAT1 , ZFAS1, SNHG7, SNHG8, and SNHG25 modulating immune function in classical monocyte, NK T, proliferating NK, plasmablast, naive, and activated B/T cells. Interestingly, we found invariant lncRNAs (no significant change in expression across conditions) regulating essential housekeeping functions (for example, HOTAIR, NRAV, SNHG27, SNHG28, and UCA1 ) in infected and recovered individuals. Despite similar repeat element abundance, variant lncRNAs displayed higher Alu content, suggesting increased interactions with proximal and distal genes, crucial for immune response modulation. The comparable repeat abundance but distinct expression levels of variant and invariant lncRNAs highlight the significance of investigating the regulatory mechanisms of invariant lncRNAs. Overall, this study offers new insights into the spatio-temporal expression patterns and functional roles of lncRNAs in SARS-CoV-2-infected and recovered individuals while highlighting the importance of invariant lncRNAs in the disease context.