Timing of Illness Onset Influences Leukocyte Destruction in Sepsis

Background The clinical significance of leukocyte destruction morphology in routine peripheral blood smears remains underexplored. This study aimed to systematically quantify leukocyte destruction and correlate these findings with clinical course, etiology, and outcome in patients with suspected sepsis.

This was a retrospective observational study involving 30 intensive care unit (ICU) patients with suspected sepsis. Peripheral blood smear findings were evaluated chronologically, with the day of blood culture collection designated as Day 0, followed by four distinct phases. Leukocyte destruction was defined as clear evidence of cytoplasmic or nuclear dissolution. Correlations were assessed with 28-day prognosis, etiology (infectious vs. non-infectious), and symptom onset (acute [no preceding symptoms before admission] vs. non-acute [preceding symptoms present]).

Leukocyte destruction showed no significant difference concerning 28-day mortality or etiology. However, it was significantly more frequent in acute onset cases within the first 48 hours (7.0% vs. 4.1%, p<0.05). Conversely, cases with toxic granulation were significantly more common in non-acute onset cases within the first 48 hours (70% vs. 14%, p<0.01).

Leukocyte destruction in acute onset and toxic granulation in non-acute onset offer potential diagnostic insights. These findings suggest uncharacterized leukocyte maturation or differentiation pathways influenced by illness timing, warranting further research for biomarker discovery and pathophysiology. Competing Interest Statement The authors have declared no competing interest. Funding Statement This research was supported by a Grant-in-Aid for Challenging Exploratory Research (grant number 15K15381 to YM). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the ethics committee of Nagasaki University Hospital (approval number, 14102792). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Al authors meet the above ICMJE authorship criteria. Data Availability All data produced in the present work are contained in the manuscript Abbreviations - ICU - intensive care unit - NETs - neutrophil extracellular traps - COVID-19 - Coronavirus disease 2019 - EDTA-2K - ethylenediaminetetraacetic acid dipotassium salt dihydrate