Leukocyte Activation Profile Assessed by Raman Spectroscopy Helps Diagnosing Infection and Sepsis

Anuradha Ramoji; Daniel Thomas-Rüddel; Oleg Ryabchykov; Michael Bauer; Natalie Arend; Evangelos J Giamarellos-Bourboulis; Jesper Eugen-Olsen; Michael Kiehntopf; Thomas Bocklitz; Jürgen Popp; Frank Bloos; Ute Neugebauer

doi:10.1097/CCE.0000000000000394

Leukocyte Activation Profile Assessed by Raman Spectroscopy Helps Diagnosing Infection and Sepsis

Crit Care Explor. 2021 May 12;3(5):e0394. doi: 10.1097/CCE.0000000000000394. eCollection 2021 May.

Authors

Anuradha Ramoji¹, Daniel Thomas-Rüddel^{1

2}, Oleg Ryabchykov^{3

4}, Michael Bauer^{1

2}, Natalie Arend^{1

3}, Evangelos J Giamarellos-Bourboulis⁵, Jesper Eugen-Olsen⁶, Michael Kiehntopf^{1

7}, Thomas Bocklitz^{3

4}, Jürgen Popp^{1

3

4}, Frank Bloos^{1

2}, Ute Neugebauer¹

Affiliations

¹ Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.
² Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
³ Leibniz Institute of Photonic Technology Jena, (Leibniz-IPHT), Member of Leibniz Research Alliance 'Health Technologies', Jena, Germany.
⁴ Institute for Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, Jena, Germany.
⁵ 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
⁶ Clinical Research Centre, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark.
⁷ Institute for Clinical Chemistry and Laboratory Diagnostics and Integrated Biobank Jena, Jena University Hospital, Jena, Germany.

Abstract

Objectives: Leukocytes are first responders to infection. Their activation state can reveal information about specific host immune response and identify dysregulation in sepsis. This study aims to use the Raman spectroscopic fingerprints of blood-derived leukocytes to differentiate inflammation, infection, and sepsis in hospitalized patients. Diagnostic sensitivity and specificity shall demonstrate the added value of the direct characterization of leukocyte's phenotype.

Design: Prospective nonrandomized, single-center, observational phase-II study (DRKS00006265).

Setting: Jena University Hospital, Germany.

Patients: Sixty-one hospitalized patients (19 with sterile inflammation, 23 with infection without organ dysfunction, 18 with sepsis according to Sepsis-3 definition).

Interventions: None (blood withdrawal).

Measurements and main results: Individual peripheral blood leukocytes were characterized by Raman spectroscopy. Reference diagnostics included established clinical scores, blood count, and biomarkers (C-reactive protein, procalcitonin and interleukin-6). Binary classification models using Raman data were able to distinguish patients with infection from patients without infection, as well as sepsis patients from patients without sepsis, with accuracies achieved with established biomarkers. Compared with biomarker information alone, an increase of 10% (to 93%) accuracy for the detection of infection and an increase of 18% (to 92%) for detection of sepsis were reached by adding the Raman information. Leukocytes from sepsis patients showed different Raman spectral features in comparison to the patients with infection that point to the special immune phenotype of sepsis patients.

Conclusions: Raman spectroscopy can extract information on leukocyte's activation state in a nondestructive, label-free manner to differentiate sterile inflammation, infection, and sepsis.

Keywords: Raman spectroscopy; biomarker; immune response; infection and inflammation; leukocytes activation; sepsis diagnosis.