Signature Inflammatory Cytokine panel: IL-10, IL-6, VEGF and IL-8 in Covid-19

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Abstract

Objective We aimed to assess a battery of inflammatory cytokines in SARS-CoV-2 patients to determine the cytokines of prognostic and/ predictive relevance in Covid-19. Methods In a cohort of total 100 SARS-CoV-2 patients (RT-PCR confirmed) hospitalized in associated SMHS hospital of GMC Srinagar, Kashmir (North India), the level of a battery of cytokines IL-6, IL-8, IL-10, IL-1α and VEGF, TNF-α and ferritin, were estimated by Enzyme Linked Immunosorbent Assay ( ELISA) on Multimode Microplate reader. Result The deranged levels of these cytokines were mostly found in patients > 60 years of age with cough and pneumonia as the most common symptoms. Correlation analysis revealed significant association between interleukin's IL-6, IL-8 and disease severity (p = 0.002) (p = 0.007) and poor disease outcome (p = 0.04), (p = 0.009) respectively. Similar association was also found between decreased levels of VEGF and poor disease outcome (p = 0.02). Further ROC analysis, univariant and multivariant (after adjusting for age, gender and other inflammatory markers), revealed increased IL-10 (AUC = 0.72) and IL-6 (AUC = 0.70) as independent markers of both disease severity(p = 0.02) (p = 0.01) and disease outcome (P = 0.03) (p = 0.02) and decreased VEGF (AUC = 0.69) as independent marker of disease outcome only (p = 0.03). Significant association of cough with IL-8 levels (p = 0.01) and of diabetes with raised ferritin levels (p = 0.01) with very high ferritin levels (> 1500ng/ml) as indicator of those that are likely to develop hyperinflammatory phenotype was found in SARS-CoV-2 patients. Conclusion We conclude ‘IL-6, IL10, VEGF and IL-8’ as the signature inflammatory cytokine panel in Covid-19. An increased IL-10, IL-6 levels proved to be equally significant independent prognosticators of Covid − 19 severity and predictors of poor disease outcome and decreased VEGF level as predictors of poor disease outcome in SARS-CoV-2 patients. Testing of the signature inflammatory cytokine panel is, therefore, recommended for optimal clinical decision making in Covid-19.

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