The Role of Immunological and Clinical Biomarkers to Predict Clinical COVID-19 Severity and Response to Therapy—A Prospective Longitudinal Study

• Main Authors: Ana Copaescu, Fiona James, Effie Mouhtouris, Sara Vogrin, Olivia C. Smibert, Claire L. Gordon, George Drewett, Natasha E. Holmes, Jason A. Trubiano
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-03-01
• Series: Frontiers in Immunology
• Subjects: SARS-CoV-2; interleukin-6; C-reactive protein; cytokine storm; Staphylococcus aureus bacteraemia; sepsis
• Online Access: https://www.frontiersin.org/articles/10.3389/fimmu.2021.646095/full

BackgroundThe association of pro-inflammatory markers such as interleukin-6 (IL-6) and other biomarkers with severe coronavirus disease 2019 (COVID-19) is of increasing interest, however their kinetics, response to current COVID-related treatments, association with disease severity and comparison with other disease states associated with potential cytokine storm (CS) such as Staphylococcus aureus bacteraemia (SAB) are ill-defined.MethodsA cohort of 55 hospitalized SARS-CoV-2 positive patients was prospectively recruited – blood sampling was performed at baseline, post-treatment and hospital discharge. Serum IL-6, C-reactive protein (CRP) and other laboratory investigations were compared between treatment groups and across timepoints. Acute serum IL-6 and CRP levels were then compared to those with suspected COVID-19 (SCOVID) and age and sex matched patients with SAB and patients hospitalized for any non-infectious condition (NIC).ResultsIL-6 was elevated at admission in the SARS-CoV-2 cohort but at lower levels compared to matched SAB patients. Median (IQR) IL-6 at admission was 73.89 pg/mL (30.9, 126.39) in SARS-CoV-2 compared to 92.76 pg/mL (21.75, 246.55) in SAB (p=0.017); 12.50 pg/mL (3.06, 35.77) in patients with NIC; and 95.51 pg/mL (52.17, 756.67) in SCOVID. Median IL-6 and CRP levels decreased between admission and discharge timepoints. This reduction was amplified in patients treated with remdesivir and/or dexamethasone. CRP and bedside vital signs were the strongest predictors of COVID-19 severity.ConclusionsKnowledge of the kinetics of IL-6 did not offer enhanced predictive value for disease severity in COVID-19 over common investigations such as CRP and vital signs.