Abstract
ObjectiveTo provide epidemiological data of infants < 90 days of age with suspected late-onset sepsis (LOS) and evaluate distinct immunological specificities. We hypothesized that previously healthy infants < 3 months of age with sepsis have a yet undefined immunological predisposition; e.g. differences in lymphocyte subsets including regulatory T cells.MethodsWe performed an exploratory, single center study between January 1st, 2019 and June 1st, 2021. Routine diagnostics included conventional culture (blood, cerebrospinal fluid, urine), PCR and inflammatory markers in infants < 90 days of age with suspected sepsis. We additionally analyzed lymphocyte subsets and CD4+ CD25+ forkhead box protein (FoxP3)+ Tregs at admission for sepsis workup as compared to age-matched controls.ResultsA convenience sample cohort of n= 51 infants with sepsis workup was enrolled. Invasive bacterial infection (IBI) was diagnosed in 25 (49.0%) patients including two infants with a rhinovirus co-infection and viral infection in 14 (27.5%) neonates. No infectious cause was found in 12 cases. Infants with suspected LOS displayed a decreased abundance of CD4+ FoxP3+ T cells as compared to controls, which was most pronounced in the subgroup of infants with IBI. We also noticed elevated HLA-DR-positive CD3+ cells in infants with LOS and a higher CD4/CD8-ratio in infants with viral infection as compared to healthy controls. Infants with viral infections had a higher number of natural killer cells as compared to infants with IBI.ConclusionOur exploratory data support the concept of a potential immaturity state and failed immune tolerance development for young infants with LOS. Future large-scale studies are needed to elucidate pre-sepsis conditions and to target the microbiome-immunity interplay as a potential risk pattern.
Highlights
Episodes with suspected infections are highly relevant in early infancy, in the first three months of life [1]
There are previous studies indicating that 7-13% of infants < 90 days of age have invasive bacterial infection (IBI; including urinary tract infection, Urinary tract infection (UTI); bacteremia and/or meningitis) [3, 6] but often causes of fever remain unknown
Since Regulatory T cell (Treg) play a role for a permissive physiological colonization of young infants [29, 30], we propose that reduced Treg quantities may represent a dysregulation pattern of the mutual immune-microbiome interaction as hallmark of susceptibility to IBI
Summary
Episodes with suspected infections are highly relevant in early infancy, in the first three months of life [1]. Diagnostic approaches are imprecise due to low sensitivity of cultures and limited specificity for laboratory markers, e.g. C-reactive protein or procalcitonin [2]. As infections in young infants often have a fulminant course, antibiotic treatment is initiated as soon as clinical suspicion is evident [3,4,5]. Diagnostic markers or signatures to clearly differentiate between invasive bacterial infection (IBI), viral infection or no infection are lacking. Molecular biology tools (e.g. multiplex pathogen-PCR; nextgeneration sequencing) are cost-intensive and not available as specific bedside tests to guide a medical decision for antibiotic treatment [5]. The diagnosis of a viral infection may help to discontinue antibiotic therapies and reduce the total exposure in these infants [7]
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