Clinical variants of sepsis and their determining factors

Introduction. Early recognition of variants of clinical manifestations of sepsis is essential for the correct choice of strategy and tactics of its treatment.

The objective was to analyze the causes and manifestations of various variants of the course of sepsis and to assess the dependence of its outcomes on these factors.

Materials and methods. A retrospective analysis of 189 medical records of patients with sepsis was conducted. Clinical recovery within 14 days occurred in 63 of them (group 1), and death – in 46 (group 2). 80 patients developed a chronic critical illness (CCI, group 3), which resulted in recovery in 23 cases and death in 57 cases. Demographic and anthropometric parameters, reasons for hospitalization, severity and type of comorbidities, manifestations of organ dysfunction (SOFA), source of infection, microbiological test results, and laboratory data were assessed. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), NLPR index (NLR x platelets), aggregate index of systemic inflammation (AISI: neutrophils x monocytes x platelets/lymphocytes), and multi-inflammatory index (MII-1: NLR x CRP, g/L) were calculated at admission and over time. ROC analysis and multivariate logistic regression analysis were used to assess the relationship between sepsis outcomes and the initial values of these factors and the rate of their change during observation and treatment.

Results. No significant differences were found between the groups in initial clinical and laboratory parameters. Differences in the dynamics of sepsis progression became apparent within the first few days after the start of treatment. Despite the predictable changes in both laboratory data and composite indices corresponding to the severity of sepsis manifestations, no significant association was established between changes in most of them and the trajectory of the septic process. It was only established that ΔCRP values can predict early recovery, and the NLPR index on day 4 can predict mortality. Simultaneous use of several indices demonstrated their association with outcome more clearly (CRP + NLPR + Δ lactate for rapid recovery; CRP + NLR + AISI for early death; NLR + ΔTLR for CCI).

Conclusion. Recognizing sepsis progression variants at the onset of the disease is impossible due to the lack of a significant correlation between simple clinical and laboratory parameters and outcomes. Differences in sepsis dynamics become clearly evident by the fourth day of treatment. Lymphocyte and platelet levels, CRP, procalcitonin, as well as the NLR, TLR, NLPR, MII-1, and AISI indices and their rate of change over time, are not suitable for predicting all sepsis progression variants due to their low specificity and sensitivity; the significance of each can change dramatically depending on the specific clinical scenario.

1. Kiryachkov Yu. Yu. Composite indices of inflammation, immunity, and nutrition. Calculation formulas, interpretation, and clinical significance (literature review). Messenger of anesthesiology and resuscitation, 2025, vol. 22, no. 4, pp. 108–116. (In Russ.). https://doi.org/10.24884/2078-5658-2025-22-4-108-116.

2. Cox M. C., Brakenridge S. C., Stortz J. A. et al. Abdominal sepsis patients have a high incidence of chronic critical illness with dismal long-term outcomes // Am J Surg. – 2020. – Vol. 220, № 6. – Р. 1467–1474. http://doi.org/10.1016/j.amjsurg.2020.07.016.

3. Evans L., Rhodes А., Alhazzani W. et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021 // Intensive Care Med. – 2021. – Vol. 47, № 11. – P. 1181–1247. https://doi.org/10.1007/s00134-021-06506-y.

4. Gaieski D. F., Edwards J. M., Kallan M. J. et al. Benchmarking the incidence and mortality of severe sepsis in the United States // Crit Care Med. – 2013. – Vol. 41, № 5. – P. 1167–1174. http://doi.org/10.1097/CCM.0b013e31827c09f8.

5. Gardner A. K., Ghita G. L., Wang Z. et al. The development of chronic critical illness determines physical function, quality of life, and long-term survival among early survivors of sepsis in surgical ICUs // Crit Care Med. – 2019. – Vol. 47, № 4. – P. 566–573. http://doi.org/10.1097/CCM.0000000000003655.

6. Hotchkiss R. S., Moldawer L. L., Opal S. M. et al. Sepsis and septic shock // Nat Rev Dis Primers. – 2016. – Vol. 30, № 2. – Р. 16045. http://doi.org/10.1038/nrdp.2016.45.

7. Huang Z. et al. Prognostic value of neutrophil-to-lymphocyte ratio in sepsis: A meta-analysis // Am J Emerg Med. – 2020. – Vol. 38, № 3. – P. 641–647. http://doi.org/10.1016/j.ajem.2019.10.023.

8. Loss S. H., Nunes D. S. L., Franzosi O. S. et al. Chronic critical illness: are we saving patients or creating victims? // Rev Bras Ter Intensiva. – 2017. – Vol. 29, № 1. – P. 87–95. http://doi.org/10.5935/0103-507X.20170013.

9. Mira J. C., Gentile L. F., Mathias B. J. et al. Sepsis pathophysiology, chronic critical illness, and persistent inflammation-immunosuppression and catabolism syndrome // Crit Care Med. – 2017. – Vol. 45, № 2. – P. 253–262. http://doi.org/10.1097/CCM.0000000000002074.

10. Samuelsen A., Lehman E., Burrows P. et al. Time-dependent variation in immunoparalysis biomarkers among patients with sepsis and critical illness // Front Immunol. – 2024. – Vol. 15. – P. 1498974. http://doi.org/10.3389/fimmu.2024.

11. Sakr Y., Jaschinski U., Wittebole X. et al. Sepsis in intensive care unit patients: worldwide data from the intensive care over nations audit // Open Forum Infect Dis. – 2018. – Vol. 5, № 12. – P. 313. http://doi.org/10.1093/ofid/ofy313.

12. Stortz J. A., Mira J. C., Raymond S. L. et al. Benchmarking clinical outcomes and the immunocatabolic phenotype of chronic critical illness after sepsis in surgical intensive care unit patients // J Trauma Acute Care Surg. – 2018. – Vol. 84, № 2. – P. 342–349. http://doi.org/10.1097/TA.0000000000001758.

13. Van der Poll T., Shankar-Hari M., Wiersinga W. J. The immunology of sepsis // Immunity. – 2021. – Vol. 54, № 11. – P. 2450–2464. http://doi.org/10.1016/j.immuni.2021.10.012.

14. Vanzant E. L., Lopez C. M., Ozrazgat-Baslanti T. et al. Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma // J Trauma Acute Care Surg. – 2014. – Vol. 76, № 1. – P. 21–30. http://doi.org/10.1097/TA.0b013e3182ab1ab5.

15. Zhong Y., Zhong L., Zhou Y. et al. Dynamic neutrophil-to-lymphocyte-platelet ratio trajectories predict 30-day and 1-year mortality in sepsis: a retrospective cohort study based on MIMIC-IV 2.2. // BMC Infect Dis. – 2025. – Vol. 25, № 1. – P. 594. http://doi.org/10.1186/s12879-025-10987-3.