Pro-inflammatory CXCL-10, TNF-α, IL-1β, and IL-6: biomarkers of SARS-CoV-2 infection

Abstract

Currently, the world is witnessing the pandemic of COVID-19, a disease caused by the novel coronavirus SARS-CoV-2. Reported differences in clinical manifestations and outcomes in SARS-CoV-2 infection could be attributed to factors such as virus replication, infiltration of inflammatory cells, and altered cytokine production. Virus-induced aberrant and excessive cytokine production has been linked to the morbidity and mortality of several viral infections. Using a Luminex platform, we investigated plasma cytokine and chemokine levels of 27 analytes from hospitalized asymptomatic (n = 39) and mildly symptomatic (n = 35) SARS-CoV-2-infected patients (in the early phase of infection), recovered individuals (45-60 days postinfection) (n = 40), and uninfected controls (n = 36) from the city of Pune located in the state of Maharashtra in India. Levels of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α and the chemokine CXCL-10 were significantly higher, while those of the antiviral cytokines IFN-γ and IL-12 p70 were significantly lower in both asymptomatic and mildly symptomatic patients than in controls. Comparison among the patient categories revealed no difference in the levels of the cytokines/chemokines except for CXCL-10 being significantly higher and IL-17, IL-4, and VEGF being significantly lower in the mildly symptomatic patients. Interestingly, levels of all key analytes were significantly lower in recovered individuals than in those in both patient categories. Nevertheless, the level of CXCL10 was significantly higher in the recovered patients than in the controls, indicating that the immune system of SARS-CoV-2 patients may take a longer time to normalize. Our data suggest that IL-6, IL-1β, TNF-α, CXCL-10, and reduced antiviral cytokines could be used as biomarkers of SARS-CoV-2 infection.

Fig. 1

Global heat map of levels of cytokines/chemokines in SARS-CoV-2-infected patients, recovered individuals, and healthy controls

Fig. 2

Comparison of concentrations of cytokines and chemokines expressed in Log₁₀(pg/mL) in different study groups. a IL-6, b TNF-α, c CXCL-10, d IL-4, e IL-17. *p <0.05; **p < 0.005; ***p < 0.0001

Fig. 3

Receiver operating characteristic (ROC) curves for IL-1β, TNF-α, CXCL-10, and IL-4, validating their applicability as biomarkers of recent infection. a ROC curve generated by comparing concentrations of TNF-α (pg/mL) in SARS-CoV-2-infected patients with their concentrations in healthy controls reveals the inefficiency of TNF-α as a biomarker (cutoff, 29.19; sensitivity, 98.65%; specificity, 83.33%), b ROC curve generated by comparing concentrations of CXCL-10 (pg/mL) in SARS-CoV-2-infected patients with their concentrations in healthy controls reveals the efficiency of CXCL-10 as a biomarker (cutoff, 124.9; sensitivity, 97.3%; specificity, 91.67%), c ROC curve generated by comparing concentrations of IL-1β (pg/mL) in SARS-CoV-2-infected patients with their concentrations in healthy controls reveals the efficiency of IL-1β as a biomarker of infection (cutoff, 0.545; sensitivity, 91.89%; specificity, 86.11%). d ROC curve generated by comparing concentrations of IL-4 (pg/mL) in SARS-CoV-2-infected patients with their concentrations in healthy controls reveals the efficiency of IL-4 as a biomarker of infection (cutoff, 1.395; sensitivity, 97.30%; specificity, 66.67%)