Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death.

Autor:	Gisby J; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Clarke CL; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.; Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom., Medjeral-Thomas N; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.; Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom., Malik TH; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Papadaki A; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Mortimer PM; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Buang NB; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Lewis S; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Pereira M; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Toulza F; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Fagnano E; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Mawhin MA; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Dutton EE; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Tapeng L; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Richard AC; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.; CRUK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom., Kirk PD; MRC Biostatistics Unit, Forvie Way, University of Cambridge, Cambridge, United Kingdom.; Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, United Kingdom., Behmoaras J; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Sandhu E; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.; Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom., McAdoo SP; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.; Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom., Prendecki MF; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.; Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom., Pickering MC; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Botto M; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Willicombe M; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.; Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom., Thomas DC; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.; Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom., Peters JE; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.; Health Data Research UK, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Mar 11; Vol. 10. Date of Electronic Publication: 2021 Mar 11.
DOI:	10.7554/eLife.64827
Abstrakt:	End-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 (n = 256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. Two hundred and three proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3), and epithelial injury (e.g. KRT19). Machine-learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte-endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets. Competing Interests: JG, CC, NM, TM, AP, PM, NB, SL, MP, FT, EF, MM, ED, LT, AR, PK, JB, ES, MP, MP, MB, MW, DT No competing interests declared, SM reports personal fees from Celltrion, Rigel, GSK and Cello, outside the submitted work. JP has received travel and accommodation expenses and hospitality from Olink to speak at Olink-sponsored academic meetings. (© 2021, Gisby et al.)
Databáze:	MEDLINE
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