Risk factors for death caused by early onset sepsis in neonates: a retrospective cohort study

Chen, Xinhong; He, Huayun; Wei, Hong; Chen, Feng; Hu, Ya

doi:10.1186/s12879-023-08851-3

Cited by 4 publications

(1 citation statement)

References 22 publications

(29 reference statements)

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“…1H-K). These are all classical signs of organ dysfunction in septic infants (Chen et al, 2023; Li et al, 2021). In summary, survivors showed relatively stable status during the infection, whereas infected non-survivors showed clear signs of both respiratory and metabolic acidosis earlier, accompanied by vascular, kidney, and liver dysfunctions at the endpoint.…”

Section: Resultsmentioning

confidence: 99%

Regulation of host metabolism and defense strategies to survive neonatal infection

Wu,

Tien,

Bæk

et al. 2024

Preprint

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Upon infection, mammals utilize either disease resistance, which seeks to eliminate pathogens at the cost of potential tissue damage, or disease tolerance, which reduces physiological damage without killing the pathogen. Newborns, constrained by limited energy reserves, predominantly rely on disease tolerance strategies to cope with infection. However, this approach may fail as pathogen levels surpass a critical threshold, prompting a shift to dysregulated immune responses that can lead to excessive inflammation and, consequently, neonatal sepsis, a condition with significant mortality risk. The mechanisms governing the interplay between disease tolerance and resistance in newborns remain poorly understood. Here, we compare infection defense strategies of sepsis survivors and non-survivors in aStaphylococcus epidermidis-infected preterm piglet model, mimicking sepsis in preterm infants. Our findings show that compared to non-survivors, sepsis survivors showed elevated disease resistance during early infection, with a stronger disease tolerance in later stages. In contrast, animals succumbing to sepsis showed limited disease resistance after infection and weaker tolerance phenotype with dysregulated immune responses at later time points, including clear signs of respiratory and metabolic acidosis, together with exaggerated inflammation and organ dysfunctions. Hepatic transcriptomics at euthanasia revealed a strong association of tolerance phenotype in survivors with enhanced oxidative phosphorylation, dampened glycolysis and innate and adaptive immune signaling. Plasma metabolomics confirmed our transcriptomic results, highlighting a tolerance phenotype in neonatal infection survivors. This was characterized by rewired metabolic regulations that emphasize mitochondrial activities, including upregulation of the tricarboxylic acid (TCA) cycle and vital interconnected pathways. Our findings suggest potential mechanisms of host metabolism to control a delicate balance of defense strategies to survive newborn infection. Further, metabolic regulations related to disease tolerance can be exploited to discover novel therapeutics for neonatal infection.

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Section: Resultsmentioning

confidence: 99%