tetano
Editor, Senior Moderator
J Cell Mol Med
. 2022 Dec 19.
doi: 10.1111/jcmm.17622. Online ahead of print.
COVID-19 plasma proteome reveals novel temporal and cell-specific signatures for disease severity and high-precision disease management
Cristiana Iosef[SUP] 1 [/SUP], Claudio M Martin[SUP] 2 3 [/SUP], Marat Slessarev[SUP] 2 3 [/SUP], Carolina Gillio-Meina[SUP] 1 [/SUP], Gediminas Cepinskas[SUP] 2 4 [/SUP], Victor K M Han[SUP] 1 5 [/SUP], Douglas D Fraser[SUP] 1 2 5 6 7 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; disease severity; precision medicine; proteome.
. 2022 Dec 19.
doi: 10.1111/jcmm.17622. Online ahead of print.
COVID-19 plasma proteome reveals novel temporal and cell-specific signatures for disease severity and high-precision disease management
Cristiana Iosef[SUP] 1 [/SUP], Claudio M Martin[SUP] 2 3 [/SUP], Marat Slessarev[SUP] 2 3 [/SUP], Carolina Gillio-Meina[SUP] 1 [/SUP], Gediminas Cepinskas[SUP] 2 4 [/SUP], Victor K M Han[SUP] 1 5 [/SUP], Douglas D Fraser[SUP] 1 2 5 6 7 [/SUP]
Affiliations
- PMID: 36537107
- DOI: 10.1111/jcmm.17622
Abstract
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.
Keywords: COVID-19; disease severity; precision medicine; proteome.