Skip to main content
Top
Published in: BMC Infectious Diseases 1/2023

Open Access 01-12-2023 | COVID-19 | Research

Elevated interleukin (IL)-6 as a predictor of disease severity among Covid-19 patients: a prospective cohort study

Authors: Bahram Nikkhoo, Matin Mohammadi, Sabah Hasani, Naseh Sigari, Aryan Borhani, Chia Ramezani, Arian Charajoo, Shaho Badri, Farzin Rostami, Mashala Etemadi, Khaled Rahmani

Published in: BMC Infectious Diseases | Issue 1/2023

Login to get access

Abstract

Background

accompanied to the spreading of coronavirus disease 2019 (Covid-19) in the world, identifying factors related to the severity of the disease is one of the interests of physician and medical researchers. We hypothesized that interleukin 6 serum level is associated with severe outcome.

Methods

In this longitudinal prospective cohort study we enrolled 208 confirmed COVID-19 patients who were admitted to the Tohid Hospital (Sanandaj, Iran). Patients were classified into two groups based on IL-6 value in the first day of admission, elevated (n = 107) or not elevated/normal (n = 101), and followed until the occurrence of final outcome (death or discharge from the hospital). Data were analyzed using univariate methods, Chi-squared and independent two sample T test. The relationship between the independent variables and our interesting outcomes were investigated by multiple linear and penalized logistic regression modeling.

Results

A total of 208 patients, 51% female and mean age 53.6 ± 16.3 years, including 107 elevated and 101 non-elevated IL-6 patients, were followed. No significant difference was observed between the two groups in demographic and clinical characteristics. Although not significant, logistic regression results showed that the chance of death occurrence among patients with elevated IL-6 are 3.91 times higher. According to the multiple linear regression modeling, elevated IL-6 significantly increased the duration of hospital stay (P = 0.02). Frequency of ICU admission (P = 0.04) and mean of ICU stay (P = 0.8) are also higher in elevated IL-6 group.

Conclusion

This study revealed that elevated IL-6 is significantly related to prolongation of hospital stay in Covid-19 patients. Although not significant, the occurrence of death among patients who had increased IL-6 in the time of admission was higher than patients with normal or lower serum levels of IL-6.
Literature
1.
go back to reference Ciotti M et al. The COVID-19 pandemic 2020. 57(6): p. 365–388. Ciotti M et al. The COVID-19 pandemic 2020. 57(6): p. 365–388.
3.
go back to reference Team EJCCw. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19)—China, 2020. 2020. 2(8): p. 113. Team EJCCw. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19)—China, 2020. 2020. 2(8): p. 113.
4.
go back to reference Xu Z, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet respiratory medicine. 2020;8(4):420–2.CrossRefPubMedPubMedCentral Xu Z, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet respiratory medicine. 2020;8(4):420–2.CrossRefPubMedPubMedCentral
5.
go back to reference Yang X et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. 2020. 8(5): p. 475–81. Yang X et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. 2020. 8(5): p. 475–81.
6.
go back to reference Jamilloux Y, et al. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun rev. 2020;19(7):102567.CrossRefPubMedPubMedCentral Jamilloux Y, et al. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun rev. 2020;19(7):102567.CrossRefPubMedPubMedCentral
7.
go back to reference Gu Y, et al. Role of the innate cytokine storm induced by the influenza a virus. Viral Immunol. 2019;32(6):244–51.CrossRefPubMed Gu Y, et al. Role of the innate cytokine storm induced by the influenza a virus. Viral Immunol. 2019;32(6):244–51.CrossRefPubMed
8.
go back to reference Uciechowski P, Dempke WC. Interleukin-6: a masterplayer in the cytokine network. Oncology. 2020;98(3):131–7.CrossRefPubMed Uciechowski P, Dempke WC. Interleukin-6: a masterplayer in the cytokine network. Oncology. 2020;98(3):131–7.CrossRefPubMed
9.
go back to reference Luo P et al. March 2020, posting date. Tocilizumab treatment in COVID-19: a single center experience. J Med Virol doi.10. Luo P et al. March 2020, posting date. Tocilizumab treatment in COVID-19: a single center experience. J Med Virol doi.10.
10.
go back to reference Neurath MF, Finotto S. IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer. Cytokine Growth Factor Rev. 2011;22(2):83–9.CrossRefPubMed Neurath MF, Finotto S. IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer. Cytokine Growth Factor Rev. 2011;22(2):83–9.CrossRefPubMed
11.
go back to reference Zhu J et al. Elevated interleukin-6 is associated with severity of COVID-19: a meta-analysis. 2021. 93(1): p. 35. Zhu J et al. Elevated interleukin-6 is associated with severity of COVID-19: a meta-analysis. 2021. 93(1): p. 35.
12.
go back to reference Liu B, et al. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS). J Autoimmun. 2020;111:102452.CrossRefPubMedPubMedCentral Liu B, et al. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS). J Autoimmun. 2020;111:102452.CrossRefPubMedPubMedCentral
13.
go back to reference Xiong Y et al. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. 2020. 9(1): p. 761–70. Xiong Y et al. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. 2020. 9(1): p. 761–70.
14.
go back to reference Coomes EA. and H.J.R.i.m.v. Haghbayan, Interleukin-6 in COVID-19: a systematic review and meta-analysis 2020. 30(6): p. 1–9. Coomes EA. and H.J.R.i.m.v. Haghbayan, Interleukin-6 in COVID-19: a systematic review and meta-analysis 2020. 30(6): p. 1–9.
15.
go back to reference Ulhaq ZS. and G.V.J.M.e.m.i. Soraya, Interleukin-6 Is a Potential Biomarker of COVID-19 Progression: Evidence from a Meta-Analysis 2020. 3562887(10.2139). Ulhaq ZS. and G.V.J.M.e.m.i. Soraya, Interleukin-6 Is a Potential Biomarker of COVID-19 Progression: Evidence from a Meta-Analysis 2020. 3562887(10.2139).
16.
go back to reference Chen X, et al. Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients. Clinical infectious diseases; 2020. Chen X, et al. Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients. Clinical infectious diseases; 2020.
17.
go back to reference Coomes EA, Haghbayan H. Interleukin-6 in COVID‐19: a systematic review and meta‐analysis. Rev Med Virol. 2020;30(6):1–9.CrossRefPubMed Coomes EA, Haghbayan H. Interleukin-6 in COVID‐19: a systematic review and meta‐analysis. Rev Med Virol. 2020;30(6):1–9.CrossRefPubMed
18.
go back to reference Herold T, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020;146(1):128–36. e4.CrossRefPubMedPubMedCentral Herold T, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020;146(1):128–36. e4.CrossRefPubMedPubMedCentral
19.
go back to reference Lagunas-Rangel FA. and V.J.J.o.m.v. Chávez‐Valencia, High IL-6/IFN-γ ratio could be associated with severe disease in COVID-19 patients. 2020. 92(10): p. 1789. Lagunas-Rangel FA. and V.J.J.o.m.v. Chávez‐Valencia, High IL-6/IFN-γ ratio could be associated with severe disease in COVID-19 patients. 2020. 92(10): p. 1789.
20.
22.
go back to reference Ulhaq ZS, Soraya GV. Interleukin-6 as a potential biomarker of COVID-19 progression. Med et maladies infectieuses. 2020;50(4):382.CrossRef Ulhaq ZS, Soraya GV. Interleukin-6 as a potential biomarker of COVID-19 progression. Med et maladies infectieuses. 2020;50(4):382.CrossRef
23.
go back to reference Bourgonje AR et al. Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). 2020. 251(3): p. 228–48. Bourgonje AR et al. Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). 2020. 251(3): p. 228–48.
24.
go back to reference Xia C, et al. Involvement of interleukin 6 in hepatitis B viral infection. Cell Physiol Biochem. 2015;37(2):677–86.CrossRefPubMed Xia C, et al. Involvement of interleukin 6 in hepatitis B viral infection. Cell Physiol Biochem. 2015;37(2):677–86.CrossRefPubMed
25.
go back to reference Gong J, et al. Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19: a retrospective study. BMC Infect Dis. 2020;20(1):1–7.CrossRef Gong J, et al. Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19: a retrospective study. BMC Infect Dis. 2020;20(1):1–7.CrossRef
26.
go back to reference Huang C, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020;395(10223):497–506.CrossRef Huang C, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020;395(10223):497–506.CrossRef
27.
go back to reference Zhou F, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The lancet. 2020;395(10229):1054–62.CrossRef Zhou F, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The lancet. 2020;395(10229):1054–62.CrossRef
28.
go back to reference Wang D, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan. China. 2020;323(11):1061–9. Wang D, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan. China. 2020;323(11):1061–9.
29.
go back to reference Chen T et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study 2020. 368. Chen T et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study 2020. 368.
30.
go back to reference El-Shabrawy M et al. Interleukin-6 and C-reactive protein/albumin ratio as predictors of COVID-19 severity and mortality. 2021. 15: p. 1–7. El-Shabrawy M et al. Interleukin-6 and C-reactive protein/albumin ratio as predictors of COVID-19 severity and mortality. 2021. 15: p. 1–7.
31.
go back to reference Gao Yd et al. Risk factors for severe and critically ill COVID-19 patients: a review. 2021. 76(2): p. 428–55. Gao Yd et al. Risk factors for severe and critically ill COVID-19 patients: a review. 2021. 76(2): p. 428–55.
32.
go back to reference Ghazanfari T et al. Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality 2021: p. 46–66. Ghazanfari T et al. Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality 2021: p. 46–66.
33.
go back to reference Rostamian A et al. Interleukin-6 as a Potential Predictor of COVID-19 disease severity in hospitalized patients and its association with clinical laboratory routine tests. 2020. 3(1): p. 29–36. Rostamian A et al. Interleukin-6 as a Potential Predictor of COVID-19 disease severity in hospitalized patients and its association with clinical laboratory routine tests. 2020. 3(1): p. 29–36.
Metadata
Title
Elevated interleukin (IL)-6 as a predictor of disease severity among Covid-19 patients: a prospective cohort study
Authors
Bahram Nikkhoo
Matin Mohammadi
Sabah Hasani
Naseh Sigari
Aryan Borhani
Chia Ramezani
Arian Charajoo
Shaho Badri
Farzin Rostami
Mashala Etemadi
Khaled Rahmani
Publication date
01-12-2023
Publisher
BioMed Central
Keyword
COVID-19
Published in
BMC Infectious Diseases / Issue 1/2023
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-023-08294-w

Other articles of this Issue 1/2023

BMC Infectious Diseases 1/2023 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine