Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study.
Angiogenesis
; 25(4): 503-515, 2022 11.
Article
in English
| MEDLINE | ID: covidwho-1899208
ABSTRACT
AIMS:
Although coronavirus disease 2019 (COVID-19) and bacterial sepsis are distinct conditions, both are known to trigger endothelial dysfunction with corresponding microcirculatory impairment. The purpose of this study was to compare microvascular injury patterns and proteomic signatures in COVID-19 and bacterial sepsis patients. METHODS ANDRESULTS:
This multi-center, observational study included 22 hospitalized adult COVID-19 patients, 43 hospitalized bacterial sepsis patients, and 10 healthy controls from 4 hospitals. Microcirculation and glycocalyx dimensions were quantified via intravital sublingual microscopy. Plasma proteins were measured using targeted proteomics (Olink). Coregulation and cluster analysis of plasma proteins was performed using a training-set and confirmed in a test-set. An independent external cohort of 219 COVID-19 patients was used for validation and outcome analysis. Microcirculation and plasma proteome analysis found substantial overlap between COVID-19 and bacterial sepsis. Severity, but not disease entity explained most data variation. Unsupervised correlation analysis identified two main coregulated plasma protein signatures in both diseases that strictly counteract each other. They were associated with microvascular dysfunction and several established markers of clinical severity. The signatures were used to derive new composite biomarkers of microvascular injury that allow to predict 28-day mortality or/and intubation (area under the curve 0.90, p < 0.0001) in COVID-19.CONCLUSION:
Our data imply a common biological host response of microvascular injury in both bacterial sepsis and COVID-19. A distinct plasma signature correlates with endothelial health and improved outcomes, while a counteracting response is associated with glycocalyx breakdown and high mortality. Microvascular health biomarkers are powerful predictors of clinical outcomes.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Sepsis
/
COVID-19
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Limits:
Adult
/
Humans
Language:
English
Journal:
Angiogenesis
Journal subject:
Hematology
Year:
2022
Document Type:
Article
Affiliation country:
S10456-022-09843-8
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