技术资料

Graphical abstract Summary of the study. Peripheral blood neutrophils from >200 hospitalised patients across three patient groups (coronavirus disease 2019 (COVID-19),non-COVID-19 lower respiratory tract infection (LRTI) and matched controls) were comprehensively profiled using mass spectrometry,revealing novel proteomic changes in acute and convalescent COVID-19. DIA: data-independent acquisition; TLR: Toll-like receptor; ARG: arginase; TGF: transforming growth factor; IFN: interferon. BackgroundNeutrophils are important in the pathophysiology of coronavirus disease 2019 (COVID-19),but the molecular changes contributing to altered neutrophil phenotypes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We used quantitative mass spectrometry-based proteomics to explore neutrophil phenotypes immediately following acute SARS-CoV-2 infection and during recovery.MethodsProspective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May to December 2020). Patients were enrolled within 96 h of admission,with longitudinal sampling up to 29 days. Control groups comprised non-COVID-19 acute lower respiratory tract infection (LRTI) and age-matched noninfected controls. Neutrophils were isolated from peripheral blood and analysed using mass spectrometry. COVID-19 severity and recovery were defined using the World Health Organization ordinal scale.ResultsNeutrophil proteomes from 84 COVID-19 patients were compared to those from 91 LRTI and 42 control participants. 5800 neutrophil proteins were identified,with >1700 proteins significantly changed in neutrophils from COVID-19 patients compared to noninfected controls. Neutrophils from COVID-19 patients initially all demonstrated a strong interferon signature,but this signature rapidly declined in patients with severe disease. Severe disease was associated with increased abundance of proteins involved in metabolism,immunosuppression and pattern recognition,while delayed recovery from COVID-19 was associated with decreased granule components and reduced abundance of metabolic proteins,chemokine and leukotriene receptors,integrins and inhibitory receptors.ConclusionsSARS-CoV-2 infection results in the sustained presence of circulating neutrophils with distinct proteomes suggesting altered metabolic and immunosuppressive profiles and altered capacities to respond to migratory signals and cues from other immune cells,pathogens or cytokines. Tweetable abstractHigh-resolution mass spectrometry analysis of peripheral blood neutrophils from >200 individuals provides novel insights into neutrophil phenotypes during acute COVID-19 and reveals that altered neutrophils persist in convalescent COVID-19 patients https://bit.ly/3QSSq9W View Publication