Contributing to research themes:
This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.
Neutrophils are important in the pathophysiology of COVID19 but the molecular changes contributing to altered neutrophil phenotypes following SARS-CoV-2 infection are not fully understood.
To use quantitative mass spectrometry-based proteomics to explore neutrophil phenotypes following acute SARS-CoV-2 infection and during recovery.
Prospective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May 2020-December 2020). Patients were enrolled within 96 hours of admission, with longitudinal sampling up to 29 days. Control groups comprised non-COVID19 acute lower respiratory tract infection (LRTI) and age-matched non-infected controls. Neutrophils isolated from peripheral blood were processed for mass spectrometry. COVID19 severity and recovery were defined using the WHO ordinal scale.
Measurements and Main Results:
84 COVID19 patients were included and compared to 91 LRTI patients and 42 controls. 5,800 neutrophil proteins were identified and 1,748 proteins were significantly different (q-value<0.05) in neutrophils from COVID19 patients compared to those of non-infected controls, including a robust interferon response at baseline, which was lost in severe patients one week after enrolment. Neutrophil changes associated with COVID19 disease severity and prolonged illness were characterized and candidate targets for modulation of neutrophil function were identified. Delayed recovery from COVID19 was associated with changes in metabolic and signalling proteins, complement, chemokine and leukotriene receptors, integrins and inhibitory receptors.
SARS-CoV-2 infection results in the sustained presence of recirculating neutrophils with distinct metabolic profiles and altered capacities to respond to migratory signals and cues from other immune cells, pathogens or cytokines.