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This study employed high\u2010throughput single\u2010cell Raman spectroscopy to analyze the biochemical profiles of peripheral blood leukocytes from patients with non\u2010COVID\u201019 and COVID\u201019\u2010associated sepsis. Leukocytes were assessed at multiple timepoints, including the acute phase (Days 3 and 7 after sepsis onset) and late recovery phase (6 and 12 months after sepsis onset). Raman spectroscopic profiles of leukocytes showed clear separation between healthy controls and sepsis patients during the acute phase with high balanced accuracy (BAcc: 95%\u201398%). Spectral differences between acute and recovery phases (BAcc: 84%\u201397%) and between recovery\u2010phase leukocytes and those from healthy controls (BAcc: 81%\u201390%) were also observed, indicating long\u2010lasting molecular alterations. Furthermore, distinct profiles were identified between non\u2010COVID\u201019 and COVID\u201019\u2010associated sepsis during the acute phase (BAcc: 65%\u201371%) and in the late\u2010recovery phase (BAcc: 71%\u201383%). These findings demonstrate that Raman spectroscopy enables label\u2010free, high\u2010throughput profiling of leukocyte biochemistry across the sepsis trajectory. This suggests that Raman spectroscopy is a promising tool for high\u2010throughput screening, offering insights into the biomolecular changes in sepsis and providing a diagnostic platform to differentiate between sepsis etiologies, a significant advancement in the field of sepsis diagnostics.<\/jats:p>","DOI":"10.1002\/biot.70105","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T06:36:53Z","timestamp":1756795013000},"source":"Crossref","is-referenced-by-count":0,"title":["Raman Spectroscopy Can Identify Acute and Persistent Biochemical Changes in Leukocytes From Patients With COVID\u201019 and Non\u2010COVID\u201019\u2010Associated Sepsis"],"prefix":"10.1002","volume":"20","author":[{"given":"Anuradha","family":"Ramoji","sequence":"first","affiliation":[{"name":"Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena Member of the Leibniz Centre for Photonics in Infection Research (LPI) Jena 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