Omicron induced distinct immune respiratory transcriptomics signatures compared to pre‐existing variants in critically ill COVID‐19 patients

Abstract

AbstractSevere coronavirus disease 2019 (COVID‐19) is related to dysregulated immune responses. We aimed to explore the effect of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants on the immune response by nasopharyngeal transcriptomic in critically‐ill patients. This prospective monocentric study included COVID‐19 patients requiring intensive care unit (ICU) admission between March 2020 and 2022. Patients were classified according to VOC (ancestral, Alpha, Delta, and Omicron). Eighty‐eight patients with severe COVID‐19 were included after matching (on prespecified clinical criteria). Profiling of gene expression markers of innate and adaptive immune responses were investigated by respiratory transcriptomics at ICU admission. Eighty‐eight patients were included in the study after matching (ancestral [n = 24], Alpha [n = 24], Delta [n = 22], and Omicron [n = 18] variants). Respiratory transcriptomic analysis revealed distinct innate and adaptive immune profiling between variants. In comparison with the ancestral variant, there was a reduced expression of neutrophil degranulation, T cell activation, cytokines signalling pathways in patients infected with Alpha and Delta variants. In contrast, there was a higher expression of neutrophil degranulation, T and B cells activation, and inflammatory interleukins pathways in patients infected with Omicron. To conclude, Omicron induced distinct immune respiratory transcriptomics signatures compared to pre‐existing variants in patients with severe COVID‐19, pointing to an evolving pathophysiology of severe COVID‐19 in the Omicron era.