Extensive acute and sustained changes to neutrophil proteomes post-SARS-CoV-2 infection

Abstract

BackgroundNeutrophils are important in the pathophysiology of COVID-19 but the molecular changes contributing to altered neutrophil phenotypes following 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-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 non-infected controls. Neutrophils were isolated from peripheral blood and analysed by mass spectrometry. COVID-19 severity and recovery were defined using the WHO 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 non-infected controls. Neutrophils from COVID-19 patients initially all demonstrated a strong interferon (IFN) 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.