Longitudinal transcriptional changes reveal genes from the natural killer cell-mediated cytotoxicity pathway as critical players underlying COVID-19 progression.

Autor:	Medina MA; Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt, Chile., Fuentes-Villalobos F; Departamento de Microbiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile., Quevedo C; Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile., Aguilera F; Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile., Riquelme R; Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt, Chile.; Hospital Dr. Eduardo Schütz Schroeder, Puerto Montt, Chile., Rioseco ML; Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt, Chile.; Hospital Dr. Eduardo Schütz Schroeder, Puerto Montt, Chile., Barria S; Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt, Chile.; Hospital Dr. Eduardo Schütz Schroeder, Puerto Montt, Chile., Pinos Y; Hospital Base San José, Osorno, Chile., Calvo M; Instituto de Medicina, Facultad de Medicina, Universidad Austral, Valdivia, Chile., Burbulis I; Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt, Chile., Kossack C; Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt, Chile., Alvarez RA; Division of Infectious Diseases, Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, United States., Garrido JL; Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt, Chile., Barria MI; Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt, Chile.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Oct 29; Vol. 13. Date of Electronic Publication: 2024 Oct 29.
DOI:	10.7554/eLife.94242
Abstrakt:	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. Competing Interests: MM, FF, CQ, FA, RR, MR, SB, YP, MC, IB, CK, RA, JG, MB No competing interests declared (© 2024, Medina et al.)
Databáze:	MEDLINE
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