Interleukin-6 and Neutrophil–Lymphocyte Ratio in Predicting Outcome of Confirmed COVID-19 Patients
Downloads
Introduction: COVID-19 emerged as a pandemic about 2 years ago. Severe and critical COVID-19 has been associated with increased interleukin 6 (IL-6) level and neutrophil–lymphocyte ratio (NLR). This study aimed to test whether IL-6 and/or NLR are associated with COVID-19 mortality.
Methods: Subjects were COVID-19 patients with suspected Omicron variant infection that were hospitalized at Dr. Moewardi Hospital from October 2021 to March 2022. According to their medical records, subjects were divided into survivor and non-survivor groups. Serum level of IL-6 and NLR at admission were recorded, compared, and analyzed for association with mortality.
Results: Seventy-four respondents, average age 53.07 ± 16.2 years, joined the research. The area under curve (AUC) value of IL-6 was 0.740, with a cut-off value of 42.00 mg/dL (73.9% sensitivity; 70.6% specificity). The AUC value of NLR was 0.721, with a cut-off value of 5.51 (73.9% sensitivity; 60.8% specificity). IL-6 had a higher odds ratio than NLR as a risk factor for mortality (6.80 [95% CI 2.24–20.61; p < 0.001]; 4.39 [95% CI 1.48–13.03; p < 0.001], respectively). The correlation between IL-6 and NLR had an r-value of 0.164 (p = 0.164).
Conclusion: There was no difference in sensitivity between IL-6 level and NLR as mortality predictors of COVID-19, but serum IL-6 level was more specific. IL-6 level correlated positively with NLR, but there was no significance.
Handayani D, Hadi D, Isbaniyah F, Burhan E, Agustin H. Penyakit virus corona 2019 [Corona virus disease 2019]. J Respir Indo. 2020;40:119–29. Indonesian.
Wang D, Hu B, Hu C, Zhu F, Liu X. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA. 2020;11:1061–9.
Tanaka T, Kishimoto T. Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases. Int J Biol Sci. 2012;8(9):1227–36.
Yang L, Liu S, Liu J, Zhang Z, Wan X, Huang B, et al. COVID-19: immunopathogenesis and immunotherapeutics. Signal Transduct Target Ther. 2020;5(1):1–8.
Ponti G, Maccaferri M, Ruini C, Tomasi A, Ozben T. Biomarkers associated with COVID-19 disease progression. Crit Rev Clin Lab Sci. 2020;1:1–12.
Liu J, Liu Y, Xiang P, Pu L, Xiong H. Neutrophil to lymphocyte ratio predicts critical illness with 2019 coronavirus disease in the early stage. BMC Pulm Med. 2020;3:1– 12.
Jurado A, Martín MC, Abad-Molina C, Orduña A, Martínez A, Ocaña E, et al. COVID-19: age, interleukin-6, C-reactive protein, and lymphocytes as key clues from a multicentre retrospective study. Immun Ageing. 2020;17(1):1–15.
Luís R, Rodolpho JMDA, Tatsuo L, Carolina A, Moreno B, Cominetti MR, et al. Since January 2020, Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company’s public news and information. 2020;(January).
Pera A, Campos C, López N, Hassouneh F, Alonso C, Tarazona R, et al. Immunosenescence: implications for response to infection and vaccination in older people. Maturitas. 2015 Sep;82(1):50–5.
Koff WC, Williams MA. Covid-19 and immunity in aging populations—a new research agenda. N Engl J Med. 2020;383(9):804–5.
Crooke SN, Ovsyannikova IG, Poland GA, Kennedy RB. Immunosenescence and human vaccine immune responses. Immun Ageing. 2019;16(1):1–16.
Ziuzia-Januszewska L, Januszewski M, Sosnowska-Nowak J, Janiszewski M, Dobrzyński P, Jakimiuk AA, et al. COVID-19 severity and mortality in two pandemic waves in Poland and predictors of poor outcomes of SARS-CoV-2 infection in hospitalised young adults. Viruses. 2022;14(8):1700.
Cunningham JW, Vaduganathan M, Claggett BL, Jering KS, Bhatt AS, Rosenthal N, et al. Clinical outcomes in young US adults hospitalised with COVID-19. JAMA Intern Med. 2020 Sep;181(3):379–81.
Liu Z, Liu J, Ye L, Yu K, Luo Z, Liang C, et al. Predictors of mortality for hospitalised young adults aged less than 60 years old with severe COVID-19: a retrospective study. J Thorac Dis. 2021 Jun;13(6):3628–42.
Altonen BL, Arreglado TM, Leroux O, Murray-Ramcharan M, Engdahl R. Characteristics, comorbidities and survival analysis of young adults hospitalised with COVID-19 in New York City. PLoS One [Internet]. 2020 Dec;15:1–16. Available from: http://dx.doi.org/10.1371/journal.pone.0243343
Peng M, He J, Xue Y, Yang X, Liu S, Gong Z. Role of hypertension on the severity of COVID-19: a review. J Cardiovasc Pharmacol. 2021;78(5):e648–55.
Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020 Apr;8(4):e21.
Yaribeygi H, Sathyapalan T, Jamialahmadi T, Sahebkar A. The impact of diabetes mellitus in COVID-19: a mechanistic review of molecular interactions. J Diabetes Res. 2020;2020:5436832.
Arslan Y, Dogan D, Ocal N, Koc A, Ayaz T, Ozkan R, et al. The boundaries between survival and nonsurvival at 19: experience of tertiary care pandemic hospital. Int J Clin Pract. 2021 Sep;75(9):e14461.
Zhang J, Hao Y, Ou W, Ming F, Liang G, Qian Y, et al. Serum interleukin-6 is an indicator for severity in 901 patients with SARS-CoV-2 infection: a cohort study. J Transl Med [Internet]. 2020;18(1):1–8. Available from: https://doi.org/10.1186/s12967-020-02571-x
Gorham J, Moreau A, Corazza F, Peluso L, Ponthieux F, Talamonti M, et al. Interleukine-6 in critically ill COVID-19 patients: A retrospective analysis. PLoS One [Internet]. 2020;15(12 12):1–11. Available from: http://dx.doi.org/10.1371/journal.pone.0244628
Polidoro RB, Hagan RS, de Santis Santiago R, Schmidt NW. Overview: systemic inflammatory response derived from lung injury caused by SARS-CoV-2 infection explains severe outcomes in COVID-19. Front Immunol. 2020;11:1626.
Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM, et al. Targeting potential drivers of COVID-19: neutrophil extracellular traps. J Exp Med. 2020 Jun;217(6):e20200652.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet [Internet]. 2020;395(10229):1033–4. Available from: http://dx.doi.org/10.1016/S0140- 6736(20)30628-0
Tadesse Z, Bekele Bayissa A, Diriba T, Chernet N, Tsegaye S, Tsega M. Neutrophil- to-lymphocyte ratio and cut-off values as pPredictor of severity and mortality in COVID-19 patients in millennium COVID-19 care center, Addis Ababa, Ethiopia. Int J Gen Med. 2022 Aug;15:6739–55.
Yildiz H, Castanares-Zapatero D, Pierman G, Pothen L, De Greef J, Nana FA, et al. Validation of neutrophil-to-lymphocyte ratio cut-off value associated with high in- hospital mortality in COVID-19 patients. Int J Gen Med. 2021;14:5111–7.
Simadibrata DM, Calvin J, Wijaya AD, Ibrahim NAA. Neutrophil-to-lymphocyte ratio on admission to predict the severity and mortality of COVID-19 patients: a meta- analysis. Am J Emerg Med. 2021 Jan;42:60–9.
Sayah W, Berkane I. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19 . The COVID-19 resource centre is hosted on Elsevier Connect , the company' s public news and information . 2020;(January).
Purwati D. Korelasi kadar interleukin-6 dengan rasio neutrofil limfosit pada pasien COVID-19 [master’s thesis]. Universitas Andalas; 2021.
Tavakolpour S, Rakhshandehroo T, Wei EX, Rashidian M. Lymphopenia during the COVID-19 infection: what it shows and what can be learned. Immunol Lett [Internet]. 2020 Jun;225:31–2. Available from: https://doi.org/10.1016/j.imlet.2020.06.013
Luo X, Zhou W, Yan X, Guo T, Wang B, Xia H, et al. Prognostic value of C-reactive protein in patients with coronavirus 2019. Clin Infect Dis. 2020 Nov;71(16):2174–9.
Gómez-Pastora J, Weigand M, Kim J, Wu X, Strayer J, Palmer AF, et al. Hyperferritinemia in critically ill COVID-19 patients—is ferritin the product of inflammation or a pathogenic mediator? Clin Chim Acta. 2020 Oct;509:249–51.
Nor M, Haryati H. The first case of COVID-19 in South Kalimantan. J Respirasi. 2020;6(3):67–74.
Xu J-B, Xu C, Zhang R-B, Wu M, Pan C-K, Li X-J, et al. Associations of procalcitonin, C-reaction protein and neutrophil-to-lymphocyte ratio with mortality in hospitalised COVID-19 patients in China. Sci Rep. 2020 Sep;10(1):15058.
Asan A, Üstündağ Y, Koca N, Şimşek A, Sayan HE, Parildar H, et al. Do initial hematologic indices predict the severity of COVID-19 patients? Turkish J Med Sci. 2021 Feb;51(1):39–44.
Feng X, Li S, Sun Q, Zhu J, Chen B, Xiong M, et al. Immune-inflammatory parameters in COVID-19 cases: a systematic review and meta-analysis. Front Med (Lausanne). 2020 Jun 9;7:301.
Copyright (c) 2023 Harsini Harsini, Jatu Aphridasari, Artrien Adhiputri, Agung Prasetyo, Hie Sukiyanto, Aditya Sri Listyoko
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
1. The journal allows the author to hold the copyright of the article without restrictions.
2. The journal allows the author(s) to retain publishing rights without restrictions.
3. The legal formal aspect of journal publication accessibility refers to Creative Commons Attribution Share-Alike (CC BY-SA).
4. The Creative Commons Attribution Share-Alike (CC BY-SA) license allows re-distribution and re-use of a licensed work on the conditions that the creator is appropriately credited and that any derivative work is made available under “the same, similar or a compatible license”. Other than the conditions mentioned above, the editorial board is not responsible for copyright violation.
JR (