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1. Lymphocyte, procalcitonin, D-dimer and high IL-6 levels in COVID-19 patients are associated with a poor prognosis.
2. IL-6 serial measurement for COVID-19 patients may be a potential indicator for evaluating the severity and patient outcome.


The COVID-19 pandemic has affected over 760 million individuals worldwide, resulting in more than 6.8 million reported deaths. Early detection of patient deterioration can assist in predicting outcomes and prioritizing healthcare services based on evidence-based indicators. Interleukin-6 (IL-6) is a cytokine that plays a role in the inflammatory process, making it a potential parameter for assessing a patient's inflammatory state. This study aimed to analyze the characteristics, laboratory profiles, and IL-6 levels of COVID-19 patients. This study used a retrospective cohort study design with medical record data. The characteristics (n=68) and IL-6 levels (n=52) of the patients on the first, third, and sixth days of treatment were recorded consecutively. The mean age of the patients was 49 years, with the majority being male (72%) and the most prevalent comorbidity being hypertension (29%). The average duration of hospitalization was 10.94 days. Shortness of breath was the most commonly reported symptom (45.6%). The medians of neutrophil-lymphocyte ratio, C-reactive protein, procalcitonin, ferritin, and D-dimer were above normal. Significant differences were observed in lymphocytes (p=0.046), procalcitonin (p=0.023), and D-dimer (p=0.000) between survivor and non-survivor patients. Significant dynamic changes in IL-6 levels were observed from the first day to the sixth day (p=0.014) and from the third day to the sixth day (p=0.041). In conclusion, risk stratification, laboratory profiles, and IL-6 levels play a role in assessing the severity and outcomes of COVID-19 patients. 


COVID-19 pandemic IL-6 clinical characteristics human and health

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How to Cite
Triyono, E. A., Rehatta, N. M., Nabilah, & Tan, F. (2023). Clinical Profiles and Il-6 Level Analysis of Critical Covid-19 Patients Receiving Lopinavir-Ritonavir. Folia Medica Indonesiana, 59(2), 92–98.


  1. Acheampong DO, Barffour IK, Boye A, et al (2020). Male predisposition to severe COVID-19: Review of evidence and potential therapeutic prospects. Biomedicine & Pharmacotherapy 131, 110748. doi: 10.1016/j.biopha.2020. 110748.
  2. Attaway AH, Scheraga RG, Bhimraj A, et al (2021). Severe covid-19 pneumonia: Pathogenesis and clinical management. BMJn436. doi: 10.1136/ bmj.n436.
  3. Badawi A, Ryoo SG (2016). Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (M ERS-CoV): A systematic review and meta-analysis. International Journal of Infectious Diseases 49, 129–133. doi: 10.1016/j.ijid.2016.06.015.
  4. Chen X, Zhao B, Qu Y, et al (2020). Detectable serum severe acute respiratory syndrome coronavirus 2 viral load (RNAemia) is closely correlated with drastically elevated interleukin 6 level in critically ill patients with coronavirus disease 2019. Clinical Infectious Diseases 71, 1937–1942. doi: 10.1093/cid/ciaa449.
  5. Conte G, Cei M, Evangelista I, et al (2021). The meaning of D-dimer value in COVID-19. Clinical and Applied Thrombosis/Hemostasis 27, 107602962110176. doi: 10.1177/1076029621101 7668.
  6. Coomes EA, Haghbayan H (2020). Interleukin‐6 in Covid‐19: A systematic review and meta‐analysis. Reviews in Medical Virology 30, 1–9. doi: 10.1002/rmv.2141.
  7. Ding F, Feng Y, Han L, et al (2021). Early fever is associated with clinical outcomes in patients with coronavirus disease. Frontiers in Public Health. doi: 10.3389/fpubh.2021.712190.
  8. Dongelmans DA, Termorshuizen F, Brinkman S, et al (2022). Characteristics and outcome of COVID-19 patients admitted to the ICU: A nationwide cohort study on the comparison between the first and the consecutive upsurges of the second wave of the COVID-19 pandemic in the Netherlands. Annals of Intensive Care 12, 5. doi: 10.1186/s136 13-021-00978-3.
  9. Donoso NE, Arribas GI, Bernabeu AFA (2021). IL-6 and other biomarkers associated with poor prognosis in a cohort of hospitalized patients with COVID-19 in Madrid. Biomarker Insights 16, 117727192110133. doi: 10.1177/1177271921101 3363.
  10. Gorham J, Moreau A, Corazza F, et al (2020). Interleukine-6 in critically ill COVID-19 patients: A retrospective analysis ed. Lazzeri C. PLoS One 15, e0244628. doi: 10.1371/journal.pone.0244 628.
  11. Honardoost M, Janani L, Aghili R, et al (2021). The association between presence of comorbidities and COVID-19 severity: A systematic review and meta-analysis. Cerebrovascular Diseases 50, 132–140. doi: 10.1159/000513288.
  12. Hu R, Han C, Pei S, et al (2020). Procalcitonin levels in COVID-19 patients. International Journal of Antimicrobial Agents 56, 106051. doi: 10.1016/j. ijantimicag.2020.106051.
  13. Kusuma VP, Ardiany D (2021). The pathophysiology and outcomes of diabetic patients with coronavirus disease 2019 (COVID-19). Biomolecular and Health Science Journal 4, 131–136. doi: 10.20473/bhsj.v4i2.30030.
  14. Liu X, Chen Y, Tang W, et al (2020). Single-cell transcriptome analysis of the novel coronavirus (SARS-CoV-2) associated gene ACE2 expression in normal and non-obstructive azoospermia (NOA) human male testes. Science China Life Sciences 63, 1006–1015. doi: 10.1007/s11427-020-1705-0.
  15. Liu Z, Li J, Chen D, et al (2020). Dynamic interleukin-6 level changes as a prognostic indicator in patients with COVID-19. Frontiers in Pharmacology. doi: 10.3389/fphar.2020. 01093.
  16. Luporini RL, Rodolpho JM de A, Kubota LT, et al (2021). IL-6 and IL-10 are associated with disease severity and higher comorbidity in adults with COVID-19. Cytokine 143, 155507. doi: 10.1016/ j.cyto.2021.155507.
  17. Mehta P, McAuley DF, Brown M, et al (2020). COVID-19: Consider cytokine storm syndromes and immunosuppression. The Lancet 395, 1033–1034. doi: 10.1016/S0140-6736(20)30628-0.
  18. Melo AKG, Milby KM, Caparroz ALMA, et al (2021). Biomarkers of cytokine storm as red flags for severe and fatal COVID-19 cases: A living systematic review and meta-analysis ed. Chalmers J. PLoS One 16, e0253894. doi: 10.1371/journal. pone.0253894.
  19. Minister of Health of the Republic of Indonesia (2023). Pedoman Pencegahan dan Pengendalian COVID-19. Kemenkes. [Webpage]
  20. Nugroho CW, et al (2021). Optimal use of tocilizumab for severe and critical COVID-19: A systematic review and meta-analysis. F1000Research, 10, 73. doi: 10.12688/f1000 research.45046.1.
  21. Owa AB, Owa OT (2020). Lopinavir/ritonavir use in Covid-19 infection: Is it completely non-beneficial? Journal of Microbiology, Immunology and Infection 53, 674–675. doi: 10.1016/j.jmii.2020. 05.014.
  22. Ozger HS, Karakus R, Kuscu EN, et al (2021). Serial measurement of cytokines strongly predict COVID-19 outcome ed. Ito E. PLoS One 16, e0260623. doi: 10.1371/journal.pone.0260623.
  23. Park M, Thwaites RS, Openshaw PJM (2020). COVID‐19: Lessons from SARS and MERS. European Journal of Immunolpgy 50, 308–311. doi: 10.1002/eji.202070035.
  24. Poudel A, Poudel Y, Adhikari A, et al (2021). D-dimer as a biomarker for assessment of COVID-19 prognosis: D-dimer levels on admission and its role in predicting disease outcome in hospitalized patients with COVID-19 ed. Ai T. PLoS One 16, e0256744. doi: 10.1371/journal. pone.0256744.
  25. Purwani D, Sulistiawati S, Purwanto B (2021). Lower level of interleukin-6 and hepcidin found in lower density of physical exercise among athlete during pandemic of COVID-19. Folia Medica Indonesiana 57, 143–146. doi: 10.20473 /fmi. v57i2.23590.
  26. Rehman K, Akash MSH, Liaqat A, et al (2017). Role of interleukin-6 in development of insulin resistance and type 2 Diabetes Mellitus. Critical Reviews in Eukaryotic Gene Expression 27, 229–236. doi: 10.1615/CritRevEukaryotGeneExpr. 2017 019712.
  27. Sama IE, Ravera A, Santema BT, et al (2020). Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin–angiotensin–aldosterone inhibitors. European Heart Journal 41, 1810–1817. doi: 10.1093/ eurheartj/ehaa373.
  28. Santa CA, Mendes FA, Oliveira AI, et al (2021). Interleukin-6 is a biomarker for the development of fatal severe acute respiratory syndrome coronavirus 2 pneumonia. Frontiers in Immunology. doi: 10.3389/fimmu.2021.613422.
  29. Song W-J, Hui CKM, Hull JH, et al (2021). Confronting COVID-19-associated cough and the post-COVID syndrome: Role of viral neurotropism, neuroinflammation, and neuroimmune responses. The Lancet Respiratory Medicine 9, 533–544. doi: 10.1016/S2213-2600 (21)00125-9.
  30. Tanaka T, Narazaki M, Kishimoto T (2014). IL-6 in Inflammation, Immunity, and Disease. Cold Spring Harbor Perspectives in Biology 6, a016295–a016295. doi: 10.1101/cshperspect.a0 16295.
  31. The Indonesian Society of Respirology (2020). Pneumonia COVID-19. PDPI. [Webpage]
  32. Tong MK, Does Y, Engelen S, et al (2022). High procalcitonin levels associated with increased intensive care unit admission and mortality in patients with a COVID-19 infection in the emergency department. BMC Infectious Diseases 22, 165. doi: 10.1186/s12879-022071 44-5.
  33. del VDM, Kim SS, Huang HH, et al (2020). An inflammatory cytokine signature predicts COVID-19 severity and survival. Nature Medicine 26, 1636–1643. doi: 10.1038/s41591-020-1051-9.
  34. World Health Organization (2022). Therapeutics and COVID-19: Living guideline. WHO. [Webpage]
  35. Wulandari L, Hamidah B, Pakpahan C, et al (2021). Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 Patient. Human Genomics 15, 29. doi: 10.1186/s40246-021-00330-7.
  36. Xu Z, Shi L, Wang Y, et al (2020). Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine 8, 420–422. doi: 10.1016/ S2213-2600(20)30076-X.
  37. Zhong Z, Li H, Zhu J, et al (2021). Clinical characteristics of 2,459 severe or critically ill COVID-19 patients. Medicine (Baltimore) 100, e23781. doi: 10.1097/MD.0000000000023781.

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