COVID-19 plasma proteome reveals novel temporal and cell-specific signatures for disease severity and high-precision disease management.
Cristiana IosefClaudio M MartinMarat SlessarevCarolina Gillio-MeinaGediminas CepinskasVictor K M HanDouglas D FraserPublished in: Journal of cellular and molecular medicine (2022)
Coronavirus disease 2019 (COVID-19) is a systemic inflammatory condition with high mortality that may benefit from personalized medicine and high-precision approaches. COVID-19 patient plasma was analysed with targeted proteomics of 1161 proteins. Patients were monitored from Days 1 to 10 of their intensive care unit (ICU) stay. Age- and gender-matched COVID-19-negative sepsis ICU patients and healthy subjects were examined as controls. Proteomic data were resolved using both cell-specific annotation and deep-analysis for functional enrichment. COVID-19 caused extensive remodelling of the plasma microenvironment associated with a relative immunosuppressive milieu between ICU Days 3-7, and characterized by extensive organ damage. COVID-19 resulted in (1) reduced antigen presentation and B/T-cell function, (2) increased repurposed neutrophils and M1-type macrophages, (3) relatively immature or disrupted endothelia and fibroblasts with a defined secretome, and (4) reactive myeloid lines. Extracellular matrix changes identified in COVID-19 plasma could represent impaired immune cell homing and programmed cell death. The major functional modules disrupted in COVID-19 were exaggerated in patients with fatal outcome. Taken together, these findings provide systems-level insight into the mechanisms of COVID-19 inflammation and identify potential prognostic biomarkers. Therapeutic strategies could be tailored to the immune response of severely ill patients.
Keyphrases
- coronavirus disease
- sars cov
- intensive care unit
- end stage renal disease
- newly diagnosed
- respiratory syndrome coronavirus
- ejection fraction
- extracellular matrix
- immune response
- chronic kidney disease
- oxidative stress
- prognostic factors
- type diabetes
- mechanical ventilation
- risk assessment
- peritoneal dialysis
- cardiovascular disease
- case report
- inflammatory response
- coronary artery disease
- bone marrow
- smoking cessation
- cardiovascular events
- risk factors
- acute myeloid leukemia
- single cell
- acute respiratory distress syndrome
- rna seq
- deep learning