Cytokine Profile Associated with COVID-19 Severity and Outcome: A Hospital-Based Study from Kashmir, North India

Introduction: Biomarkers of prognostic and predictive relevance are needed for the practical management of COVID-19. Objective: The authors aimed to assess a battery of inflammatory cytokines in patients with SARS-CoV-2 to determine the cytokines of prognostic and predictive relevance in COVID-19. Methods: In a cohort of 100 patients with SARS-CoV-2 (RT-PCR confirmed), hospitalised in Shri Maharaja Hari Singh Hospital associated to Government Medical College Srinagar, India, the level of a battery of cytokines, IL-6, IL-8, IL-10, IL-1α, vascular endothelial growth factor (VEGF), TNF-α, and ferritin were estimated by ELISA on a multimode microplate reader. Results: The deranged levels of these cytokines were mostly found in patients >60 years of age, with cough and pneumonia as the most common symptoms. A significant association was found between IL-6 and IL-8, disease severity (p=0.002; p=0.007), and poor disease outcome (p=0.040; p=0.009), respectively. A significant association was also found between decreased levels of VEGF and poor disease outcome (p=0.020). Further receiver operating characteristic analysis, univariant and multivariant (after adjusting for age, gender, and other inflammatory markers), revealed increased IL-10 (area under the curve 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), respectively, and decreased VEGF (AUC: 0.69) as an independent marker of disease outcome (p=0.03). A significant association between cough and IL-8 (p=0.01) and IL-10 levels (p=0.03), and of diabetes and raised ferritin levels (p=0.01), with very high ferritin levels (>1500 ng/mL), was found in those who are likely to develop hyperinflammatory phenotype. Conclusion: The authors conclude that ‘IL-6, IL10, VEGF, and IL-8’ are the signature inflammatory cytokine panel/profile in COVID-19, particularly in patients from Kashmir. Increased IL-10 and IL-6 levels proved to be equally significant independent prognosticators of COVID-19 severity and outcome, and decreased VEGF levels were independent predictors of poor disease outcome in patients with SARS-CoV-2. Testing of the signature inflammatory cytokine panel is, therefore, recommended for optimal clinical decision-making in patients with COVID-19 from Kashmir, India.