Abstract
Background
Although early survival from sepsis has improved with timely resuscitation and source
control, survivors frequently experience persistent inflammation and develop chronic
critical illness. We examined whether increased copy number of endogenous alarmins,
mitochondrial DNA, and nuclear DNA are associated with the early “genomic storm” in
blood leukocytes and the development of chronic critical illness in hospitalized patients
with surgical sepsis.
Methods
A prospective, observational, cohort study of critically ill septic patients was performed
at a United States tertiary health care center. Blood samples were obtained at multiple
time points after the onset of sepsis. Droplet Digital polymerase chain reaction (Bio-Rad
Laboratories, Hercules, CA) was performed to quantify RHO (nuclear DNA) and MT-CO2 (mitochondrial DNA) copies in plasma. Leukocyte transcriptomic expression of 63 genes
was also measured in whole blood.
Results
We enrolled 112 patients with surgical sepsis. Two experienced early death, 69 recovered
rapidly, and 41 developed chronic critical illness. Both mitochondrial DNA and nuclear
DNA copy number were increased in all sepsis survivors, but early nuclear DNA, and
not mitochondrial DNA, copy number was further increased in patients who developed
chronic critical illness. Cell-free DNA copy number was associated with in-hospital
but not long-term (180-day and 365-day) mortality and were only weakly correlated
with leukocyte transcriptomics.
Conclusion
Increased cell-free DNA copy number persists in survivors of sepsis but is not strongly
associated with leukocyte transcriptomics. Nuclear DNA but not mitochondrial DNA copy
number is associated with adverse, short-term, clinical trajectories and outcomes.
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Article info
Publication history
Published online: December 31, 2019
Accepted:
November 25,
2019
Identification
Copyright
© 2019 Elsevier Inc. All rights reserved.
