Interleukin-6 Level and Neutrophil-Lymphocytes Ratio and Severity of Coronavirus Disease 19

Armina Latifah, Ida Parwati, Anna Tjandrawati, Nida Suraya


Interleukin-6 (IL-6) is a proinflammatory cytokine that plays an important role in hyperinflammation and cytokine storm in Coronavirus Disease 19 (COVID-19) patients. The neutrophil-lymphocyte ratio (NRL) describes the innate and adaptive immune responses. Elevated IL-6 and NLR levels usually indicate a severe clinical condition in COVID-19 patients. Aim of this study was to determine the correlation of IL-6 and NLR with the severity of illness in COVID-19 hospitalized patients. This was a descriptive correlative observational study with a cross-sectional design using secondary data from COVID-19 patients treated in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia, from November 2020 to October 2021. There were 225 subjects who were classified by the severity and analyzed for IL-6 levels and NLR. Median levels of IL-6 at moderate, severe, and critical levels were 4.1 pg/mL, 20.4 pg/mL, and 38.8 pg/mL, respectively. The median NLR at moderate, severe, and critical grades were respectively 4.41, 9.65, and 17.79. The correlation between IL-6, NLR, and severity was 0.441 (p<0.001) and 0.408 (p<0.001). Meanwhile, the correlation between IL-6 levels and NLR in COVID-19 was 0.230 (p<0.001). Thus, IL-6 and NRL levels have a moderate positive correlation with the severity of COVID-19, while IL-6 and NRL have a weak correlation because IL-6 is not the only factor that affects the NRL.


COVID-19, disease severity, IL-6, NRL

Full Text:



  1. IRIS. COVID-19 weekly epidemiological update. 50 ed. Geneva: World Health Organization; 2021.
  2. Bohn MK, Hall A, Sepiashvili L, Jung B, Steele S, Adeli K. Pathophysiology of COVID-19: mechanisms underlying disease severity and progression. Physiology (Bethesda). 2020;35(5):288–301. doi:10.1152/physiol.00019.2020
  3. Burhan E, Susanto AD, Isbaniah F, Nasution SA, Ginanjar E, Pitoyo CW, et al, Editors. Pedoman Tatalaksana COVID-19. 4 ed. Jakarta: PDPI, PERKI, PAPDI, PERDATIN, IDAI; 2022.
  4. Murphy K, Weaver C, Editors. Janeway’s immunobiology. 9th ed. New york: Garland science; 2016.
  5. Yang L, Liu S, Liu J, Zhang Z, Wan X, Huang B, et al. COVID-19: immunopathogenesis and Immunotherapeutics. Signal transduction and targeted therapy. 2020;5(1):1–8.
  6. Yang P-H, Ding Y-B, Xu Z, Pu R, Li P, Yan J, et al. Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19. Infectious Diseases of Poverty. 2020;9(1):161. doi:10.1186/s40249-020-00780-6
  7. Silva B, Rodrigues W, Abadia D, Alves da Silva D, Andrade E. Clinical-Epidemiology Aspect of Inpatients With Moderate or Severe COVID-19 in a Brazilian Macroregion: Disease and Countermeasures. Front Cell Infect Microbiol. 2022;12:899702. doi:10.3389/fcimb.2022.899702
  8. Jameson JL, Kasper DL, Longo DL, Fauci AS, Hauser SL, Loscalzo J, Editors. Harrison’s principles of internal medicine. 20th ed. United States: McGraw-Hill; 2018.
  9. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA. 2020;323(20):2052–9. doi:10.1001/jama.2020.6775
  10. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–62. doi:10.1016/s0140-6736(20)30566-3
  11. Liu X, Wang H, Shi S, Xiao J. Association between IL-6 and severe disease and mortality in COVID-19 disease: a systematic review and meta-analysis. Postgraduate Medical Journal. 2021:postgradmedj-2021-139939. doi:10.1136/postgradmedj-2021-139939
  12. Andriani I, Utariani A, Hanindito E, Airlangga PS. Correlation between CRP Il-6 level, severity and mortality in patients with Covid-19 infection in Indonesia. International J Scientific Advances. 2021;2(4):2708.
  13. Hashizume M. Outlook of IL-6 signaling blockade for COVID-19 pneumonia. Inflammation and Regeneration. 2020;40(1):24. doi:10.1186/s41232-020-00134-7
  14. Skevaki C, Fragkou PC, Cheng C, Xie M, Renz H. Laboratory characteristics of patients infected with the novel SARS-CoV-2 virus. J Infection. 2020;81(2):205–12. doi:
  15. Henry BM, Oliveira MHSd, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020;58(7):1021–28. doi:doi:10.1515/cclm-2020-0369
  16. Suhartono S, Wijaya I, Dalimoenthe NZ. The correlation of neutrophil-to-lymphocyte ratio (NLR) and monocytes-to-lymphocytes ratio (MLR) with disease severity in hospitalized patients with Coronavirus disease 2019 (COVID-19). Bali Med J. 2021;10(2):653–8.
  17. Liu L, Zheng Y, Cai L, Wu W, Tang S, Ding Y, et al. Neutrophil‐to‐lymphocyte ratio, a critical predictor for assessment of disease severity in patients with COVID‐19. International journal of laboratory hematology. 2021;43(2):329–35.
  18. Lanier L. The innate and adaptive immune systems. In: Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P, Editors. Molecular biology of the cell. 6 ed. New York: Garland Science; 2015. p. 1297–39.
  19. Garcia-Gordillo JA, Camiro-Zúñiga A, Aguilar-Soto M, Cuenca D, Cadena-Fernández A, Khouri LS, et al. COVID-IRS: A novel predictive score for risk of invasive mechanical ventilation in patients with COVID-19. PLOS ONE. 2021;16(4):e0248357. doi:10.1371/journal.pone.0248357
  20. Sayah W, Berkane I, Guermache I, Sabri M, Lakhal FZ, Yasmine Rahali S, et al. Interleukin-6, procalcitonin and neutrophil-to-lymphocyte ratio: Potential immune-inflammatory parameters to identify severe and fatal forms of COVID-19. Cytokine. 2021;141:155428. doi:10.1016/j.cyto.2021.155428


Article Metrics

Abstract view : 209 times
PDF - 54 times

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


Creative Commons License
MKB is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License


View My Stats