Correlation of Interleukin-6 Level with Neutrophil to Lymphocyte Ratio and Disease Severity in COVID-19 Patients

Hendrastutik Apriningsih, Nurhasan Agung Prabowo, Reviono Reviono, Brigitta Devi Anindita, Risalina Myrtha, Desy Puspa Putri, Berty Denny Hermawati


Coronavirus disease 2019 (COVID-19) causes severe acute respiratory disease in humans and has spread rapidly worldwide since its first identification in December 2019. The neutrophil-to-lymphocyte ratio (NLR) describes the balance between the severity of inflammation and the immune system to be used as an important systemic inflammatory marker. Rapid progression of clinical deterioration is characterized by severe respiratory symptoms related to high levels of pro-inflammatory cytokines, like interleukin-6 (IL-6), indicating that the occurrence of cytokine storms leads to increased mortality. This study aims to assess the correlation between IL-6 and NLR in predicting the severity of COVID-19. This prospective cohort study was conducted at the COVID-19 ward of Universitas Sebelas Maret Hospital in August–September 2021. This study involved 66 COVID-19 patients >18 years old with asymptomatic to critical degree and Charlson Comorbidity Index (CCI) value ≤3. Examination of laboratory parameters and serum IL-6 was carried out when the patient entered the Emergency Room. Statistical test with Pearson’s correlation test, significant if p<0.05. There is no significant correlation between IL-6 and NLR with p=0.56 and r=0.08, and a strong correlation between IL-6 and disease severity with p=0.000 and r=0.454. The conclusion is that IL-6 does not correlate with NLR and strongly correlates with disease severity in COVID-19 patients.


COVID-19; disease severity; interleukin-6; neutrophil-to-lymphocyte ratio

Full Text:



Ali N, Islam F. The effects of air pollution on COVID-19 infection and mortality—a review of recent evidence. Front Public Health. 2020;8:580057.

Yang B, Chang X, Huang J, Pan W, Si Z, Zhang C, et al. The role of IL-6/lymphocytes ratio in the peripheral blood of severe patients with COVID-19. Int Immunopharmacol. 2021;97:107569.

Santa Cruz A, Mendes-Frias A, Oliveira AI, Dias L, Matos AR, Carvalho A,, et al. Interleukin-6 is a biomarker for the development of fatal severe acute respiratory syndrome coronavirus 2 pneumonia. Front Immunol. 2021;12:613422.

Suhartono, Wijaya I, Dalimoenthe N. 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.

Lee H, Kim I, Kang BH, Um SJ. Prognostic value of serial neutrophil-to-lymphocyte ratio measurements in hospitalized community-acquired pneumonia. PLoS One. 2021;16(4):e0250067.

Senapathi TGA, Budiarta IG, Panji PAS, Aprilnita A. The significance of modified PIRO scoring with NLR biomarker on enhanching mortality prediction of patients with ventilator-associated pneumonia in intensive care unit. BJOA. 2018;2(3):80–5.

Nurhayatun E, Prabowo NA, Harioputro DR, Putranto W, Indarto D, Purwanto B. Neutrophil to lymphocyte ratio and Hs-CRP predict mortality in COVID-19 patients. Adv Health Sci Res. 2021;33:80–4.

Wang Y, Zhao J, Yang L, Hu J, Yao Y. Value of the neutrophil-lymphocyte ratio in predicting COVID-19 severity: a meta-analysis. Dis Markers. 2021;2021:2571912.

Ni W, Yang X, Yang D, Bao J, Li R, Xiao Y, et al. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care. 2020;24(1):422.

Cuschieri S, Grech E, Cuschieri A. Climate change, obesity, and COVID-19—global crises with catastrophic consequences. Is this the future? Atmosphere. 2021;12(1):1292.

Azwar MK, Setiati S, Rizka A, Fitriana I, Saldi SRF, Safitri ED. Clinical profile of elderly patients with COVID-19 hospitalised in Indonesia’s National General Hospital. Acta Med Indones. 2020;52(3):199–205.

Geng MJ, Wang LP, Ren X, Yu JX, Chang ZR, Zheng CJ, et al. Risk factors for developing severe COVID-19 in China: an analysis of disease surveillance data. Infect Dis Poverty. 2021;10(1):48.

Sabaka P, Koščálová A, Straka I, Hodosy J, Lipták R, Kmotorková B, et al. Role of interleukin 6 as a predictive factor for a severe course of Covid-19: restrospective data analysis of patients from a long-term care facility during Covid-19 outbreak. BMC Infect Dis. 2021;20(1):308.

Galván-Román JM, Rodríguez-García SC, Roy-Vallejo E, Marcos-Jiménez A, Sánchez-Alonso S, Fernández-Díaz C, et al. IL-6 serum levels predict severity and responses to tocilizumab in COVID-19: an observational study. J Allergy Clin Immunol. 2020;147(1):72–80.

Selanno Y, Widaningsih Y, Esa T, Arif M. Analysis of neutrophil lymphocyte ratio and absolute lymphocyte count as predictors of severity of COVID-19 patients. IJCPML. 2021;27(2):184–9.

Li J, Chen Q, Luo X, Hong X, Pan K, Lin X, et a;. Neutrophil-to-lymphocyte ratio positively correlates to age in healthy population. J Clin Lab Anal. 2015;29(6):437–43.

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 form of COVID-19. Cytokine. 2021;141:155428.

Imran MM, Ahmad U, Usman U, Ali M, Shaukat A, Gul N. Neutrophil/lymphocyte ratio—a marker of COVID-19 pneumonia severity. Int J Clin Pract. 2021;75(4):e13698.

Rubin EJ, Longo DL, Baden LR. Interleukin-6 receptor inhibition in Covid-19—cooling the inflammatory soup. N Engl J Med. 2021;384(16):1564–5.

Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020;9(1):1123–30.

Ananda RYD, Kurniati N, Hudari H, Bahar E. correlation of interleukin-6 levels with clinical features and chest X-ray imaging in coronavirus disease-19 (COVID-19) patients at Dr. Mohammad Hoesin General Hospital Palembang. Bioscientia Medicina. 2020;6(5):1799–805.

Guirao JJ, Cabrera CM, Jiménez N, Rincón L, Urra JM. High serum IL-6 values increase the risk of mortality and the severity of pneumonia in patients diagnosed with COVID-19. Mol Immunol J. 2020;228:64–8.


pISSN 2301-9123 | eISSN 2460-5441

Visitor since 19 October 2016: 

View My Stats

Free counters!

Global Medical and Health Communication is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.