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

• Published in: Frontiers in immunology Vol. 12; p. 646095
• Main Authors: Copaescu, Ana, James, Fiona, Mouhtouris, Effie, Vogrin, Sara, Smibert, Olivia C, Gordon, Claire L, Drewett, George, Holmes, Natasha E, Trubiano, Jason A
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 17.03.2021
• Subjects: Adenosine Monophosphate - analogs & derivatives; Adenosine Monophosphate - therapeutic use; Adult; Aged; Alanine - analogs & derivatives; Alanine - therapeutic use; Anti-Inflammatory Agents - therapeutic use; Antiviral Agents - therapeutic use; Bacteremia - blood; Biomarkers - blood; C-reactive protein; C-Reactive Protein - metabolism; Cohort Studies; Comorbidity; COVID-19 - blood; COVID-19 - complications; COVID-19 - physiopathology; COVID-19 Drug Treatment; cytokine storm; Dexamethasone - therapeutic use; Female; Humans; Immunology; interleukin-6; Interleukin-6 - blood; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Respiratory Distress Syndrome - blood; Respiratory Distress Syndrome - complications; SARS-CoV-2; sepsis; Severity of Illness Index; Staphylococcal Infections - blood; Staphylococcus aureus bacteraemia; SARS-CoV-2; C-reactive protein; cytokine storm; acute respiratory distress syndrome; Staphylococcus aureus bacteraemia; interleukin-6; sepsis
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.646095

The 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. A 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). IL-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. Knowledge 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.