tetano
Editor, Senior Moderator
Elife
. 2024 Oct 29:13:RP94242.
doi: 10.7554/eLife.94242. Longitudinal transcriptional changes reveal genes from the natural killer cell-mediated cytotoxicity pathway as critical players underlying COVID-19 progression
Matias A Medina[SUP] 1 [/SUP], Francisco Fuentes-Villalobos[SUP] 2 [/SUP], Claudio Quevedo[SUP] 3 [/SUP], Felipe Aguilera[SUP] 3 [/SUP], Raul Riquelme[SUP] 1 4 [/SUP], Maria Luisa Rioseco[SUP] 1 4 [/SUP], Sebastian Barria[SUP] 1 4 [/SUP], Yazmin Pinos[SUP] 5 [/SUP], Mario Calvo[SUP] 6 [/SUP], Ian Burbulis[SUP] 1 [/SUP], Camila Kossack[SUP] 1 [/SUP], Raymond A Alvarez[SUP] 7 [/SUP], Jose Luis Garrido[SUP] 1 [/SUP], Maria Ines Barria[SUP] 1 [/SUP]
Affiliations
Patients present a wide range of clinical severities in response severe acute respiratory syndrome coronavirus 2 infection, but the underlying molecular and cellular reasons why clinical outcomes vary so greatly within the population remains unknown. Here, we report that negative clinical outcomes in severely ill patients were associated with divergent RNA transcriptome profiles in peripheral immune cells compared with mild cases during the first weeks after disease onset. Protein-protein interaction analysis indicated that early-responding cytotoxic natural killer cells were associated with an effective clearance of the virus and a less severe outcome. This innate immune response was associated with the activation of select cytokine-cytokine receptor pathways and robust Th1/Th2 cell differentiation profiles. In contrast, severely ill patients exhibited a dysregulation between innate and adaptive responses affiliated with divergent Th1/Th2 profiles and negative outcomes. This knowledge forms the basis of clinical triage that may be used to preemptively detect high-risk patients before life-threatening outcomes ensue.
Keywords: COVID-19; NK; PBMC RNA-seq; human; infectious disease; microbiology.
. 2024 Oct 29:13:RP94242.
doi: 10.7554/eLife.94242. Longitudinal transcriptional changes reveal genes from the natural killer cell-mediated cytotoxicity pathway as critical players underlying COVID-19 progression
Matias A Medina[SUP] 1 [/SUP], Francisco Fuentes-Villalobos[SUP] 2 [/SUP], Claudio Quevedo[SUP] 3 [/SUP], Felipe Aguilera[SUP] 3 [/SUP], Raul Riquelme[SUP] 1 4 [/SUP], Maria Luisa Rioseco[SUP] 1 4 [/SUP], Sebastian Barria[SUP] 1 4 [/SUP], Yazmin Pinos[SUP] 5 [/SUP], Mario Calvo[SUP] 6 [/SUP], Ian Burbulis[SUP] 1 [/SUP], Camila Kossack[SUP] 1 [/SUP], Raymond A Alvarez[SUP] 7 [/SUP], Jose Luis Garrido[SUP] 1 [/SUP], Maria Ines Barria[SUP] 1 [/SUP]
Affiliations
- PMID: 39470726
- PMCID: PMC11521369
- DOI: 10.7554/eLife.94242
Patients present a wide range of clinical severities in response severe acute respiratory syndrome coronavirus 2 infection, but the underlying molecular and cellular reasons why clinical outcomes vary so greatly within the population remains unknown. Here, we report that negative clinical outcomes in severely ill patients were associated with divergent RNA transcriptome profiles in peripheral immune cells compared with mild cases during the first weeks after disease onset. Protein-protein interaction analysis indicated that early-responding cytotoxic natural killer cells were associated with an effective clearance of the virus and a less severe outcome. This innate immune response was associated with the activation of select cytokine-cytokine receptor pathways and robust Th1/Th2 cell differentiation profiles. In contrast, severely ill patients exhibited a dysregulation between innate and adaptive responses affiliated with divergent Th1/Th2 profiles and negative outcomes. This knowledge forms the basis of clinical triage that may be used to preemptively detect high-risk patients before life-threatening outcomes ensue.
Keywords: COVID-19; NK; PBMC RNA-seq; human; infectious disease; microbiology.