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. 2021 Jan 8:11:602395.
doi: 10.3389/fimmu.2020.602395. eCollection 2020.

Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients

Lili Li  1   2 , Jie Li  3 , Meiling Gao  1   2   3 , Huimin Fan  1   2 , Yanan Wang  4 , Xin Xu  1   2 , Chunfeng Chen  4 , Junxiao Liu  1   2 , Jocelyn Kim  5 , Roghiyh Aliyari  5 , Jicai Zhang  3 , Yujie Jin  3 , Xiaorong Li  1   2 , Feng Ma  1   2 , Minxin Shi  6 , Genhong Cheng  5 , Heng Yang  1   2
Affiliations

Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients

Lili Li et al. Front Immunol. .

Abstract

The widespread prevalence of coronavirus disease-2019 (COVID-19) which is caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has resulted in a severe global public health emergency. However, there are no sensitive biomarkers to predict the disease prognosis of COVID-19 patients. Here, we have identified interleukin-8 (IL-8) as a biomarker candidate to predict different disease severity and prognosis of COVID-19 patients. While serum IL-6 become obviously elevated in severe COVID-19 patients, serum IL-8 was easily detectible in COVID-19 patients with mild syndromes. Furthermore, lL-8 levels correlated better than IL-6 levels with the overall clinical disease scores at different stages of the same COVID-19 patients. Thus, our studies suggest that IL-6 and IL-8 can be respectively used as biomarkers for severe COVID-19 patients and for COVID-19 disease prognosis.

Keywords: biomarker; coronavirus disease-2019 prognosis; cytokine serum profile; cytokine storm; interleukin-6; interleukin-8; respiratory syndrome coronavirus 2.

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Conflict of interest statement

Authors YW and CC were employed by the company Suzhou Func Biotech Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Multiple cytokine profile from different clinical outcomes of SARS-CoV-2 infected patients. (A) Clinical outcomes and nucleic acid test results of four SARS-CoV-2 infected patients. The patients were divided into two groups by clinical outcomes: severe and recovered. Patient 4# died in the hospital. (B) Heatmap of cytokines in sera from COVID-19 patients during different clinical stages. Because of the death, we did not get recovered serum from patient 4#. We then added normal serum as a control. Cytokine levels were detected using Quantibody® Human Inflammation Array-3.
Figure 2
Figure 2
Cytokine levels in COVID-19 severe and recovered patients’ sera. Cytokine levels of IL-6 (A), IL-8 (B), BLC (C), MIG (D), MIP-1b (E), Eotaxin-1 (F), TNF RI (G), and MCP-1(H) in COVID-19 severe and recovered patients’ sera. Every column represents one serum sample of COVID-19 patients.
Figure 3
Figure 3
IL-8 performed better in distinguishing COVID-19 patients from healthy people. (A, B) Scatter plot of IL-6 (A) and IL-8 (B) levels detected by ELISA in healthy and COVID-19 patients’ sera. (C, D) The detectability performance of IL-6 (C) and IL-8 (D) in COVID-19 patients was estimated using ROC curve analysis and compared with the AUC. ELISA data (A, B) are shown as Mean±SEM, ****p<0.0001, unpaired Student t test.
Figure 4
Figure 4
While IL-6 represents for COVID-19 patients with severe disease conditions, IL-8 is a better indicator of overall COVID-19 diseases. (A) Heatmap of IL-6 and IL-8 levels from COVID-19 patients during different clinical stages. (B, C) The IL-6 (B) and IL-8 (C) levels among different COVID-19 patient groups. (D) Distribution of IL-6 and IL-8 levels among different COVID-19 patient groups. Dashed lines indicate the lower limit of detection for the ELISA. ELISA data (B, C) are shown as Mean±SEM, *p<0.05, ****p<0.0001, unpaired Student t test.
Figure 5
Figure 5
IL-8 may serve as a biomarker to indicate the COVID-19 disease prognosis. (A–E) IL-6 and IL-8 levels were compared with different patients’ clinical scores at multiple time points. Left Y-axis displays the concentration of cytokines: IL-6 in orange and IL-8 in green. Right Y-axis displays the clinical scores depicted in blue. X-axis displays the day numbers of COVID-19 diagnosis from the first positive PCR test.
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