Chemokine CCL2 and its receptor CCR2 in different age groups of patients with COVID-19

Abstract

Background: Despite the development of various antiviral drugs, most of them are not effective in the treatment of coronavirus disease 2019 (COVID-19) as a hyperinflammatory disorder. Chemokine (C-C motif) ligand 2 (CCL2) is one of the critical CC chemokines involved in the pathogenesis and severity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This study aimed to investigate the expression of CCL2 and CC chemokine receptor 2 (CCR2) in COVID-19 patients.

Methods: Peripheral blood samples were collected from 60 confirmed COVID-19 patients and 60 age-matched healthy subjects. The ages of the subjects were categorized as follows: up to 20 years, 20 to 40 years, 40 to 60 years, and more than 60 years. CCL2 serum levels were measured using the enzyme-linked immunosorbent assay (ELISA). CCR2 gene expression in peripheral blood mononuclear cells (PBMCs) was measured employing real-time polymerase chain reaction (PCR).

Results: In all age groups, CCL2 serum levels were significantly elevated in patients compared to healthy controls (P < 0.0001). CCL2 levels were higher in severe patients than in moderate patients. Moreover, CCR2 expression by PBMCs was higher in patients compared to control subjects. However, a significant difference between patients and controls over 60 years of age was identified (P = 0.0353). There was no significant difference in CCR2 expression between moderate and severe COVID-19 patients.

Conclusions: Taken together, the findings demonstrate that CCL2 and CCR2 are upregulated in COVID-19 patients at protein and mRNA levels, respectively. Therefore, the CCL2/CCR2 axis may be a potential therapeutic target in order to improve patient outcomes.

Keywords: CCL2; CCR2; COVID-19; Chemokine; SARS-CoV-2 infection.

Fig. 1

Serum levels of CCL2 in COVID-19 patients and healthy controls of different age groups. (A) < 20 years (B) 20–40 years (C) 40–60 years (D) > 60 years. Differences were considered statistically significant when P < 0.05 (P < 0.0001)

Fig. 2

CCR2 expression and CCL2 levels in COVID-19 patients according to gender and stages of disease. (A) The expression level of CCR2 gene in male and female COVID-19 patients. (B) The expression level of CCR2 gene in moderate and severe COVID-19 patients. (C) Serum level of CCL2 in male and female COVID-19 patients. (D) Serum level of CCL2 in moderate and severe COVID-19 patients. ns: not significant

Fig. 3

The heatmap displays the correlation coefficients between various parameters, including Age, White Blood Cell count (WBC), Fever, Oxygen saturation (O2), C-reactive protein (CRP), CCR2, and CCL2. The color scale on the right represents the strength of the correlation, ranging from − 1 (red, strong negative correlation) to + 1 (blue, strong positive correlation). Most variables showed weak or negligible correlations with one another, indicating minimal associations across the dataset

Fig. 4

CCR2 expression in PBMCs from COVID-19 patients and healthy controls. (A) < 20 years (B) 20–40 years (C) 40–60 years (D) > 60 years. Ns: not significant. * Significant difference between the two groups (P = 0.0353). The expression of CCR2 was measured by real-time PCR