Laboratory biomarkers associated with COVID-19 severity and management

Abstract

The heterogeneous disease course of COVID-19 is unpredictable, ranging from mild self-limiting symptoms to cytokine storms, acute respiratory distress syndrome (ARDS), multi-organ failure and death. Identification of high-risk cases will enable appropriate intervention and escalation. This study investigates the routine laboratory tests and cytokines implicated in COVID-19 for their potential application as biomarkers of disease severity, respiratory failure and need of higher-level care. From analysis of 203 samples, CRP, IL-6, IL-10 and LDH were most strongly correlated with the WHO ordinal scale of illness severity, the fraction of inspired oxygen delivery, radiological evidence of ARDS and level of respiratory support (p ≤ 0.001). IL-6 levels of ≥3.27 pg/ml provide a sensitivity of 0.87 and specificity of 0.64 for a requirement of ventilation, and a CRP of ≥37 mg/l of 0.91 and 0.66. Reliable stratification of high-risk cases has significant implications on patient triage, resource management and potentially the initiation of novel therapies in severe patients.

Keywords: Biomarkers; COVID-19; CRP; Cytokines; IL-10; IL-6; Intensive care; LDH.

Fig. 1

Heatmap of biochemical markers and their association with COVID-19 illness severity. Heatmap shows biochemical signatures for each patient, arranged by WHO COVID-19 severity score. Visualisation was performed using the pheatmap R package. Biomarkers values are log10 transformed, centred and scaled. No patients had WHO severity scores 0, 1 or 2 as these are non-hospitalised patients. A score of 3 is hospitalised patients requiring no oxygen therapy; a score of 4 requires oxygen therapy; 5 requires non-invasive ventilation (NIV); of 6 requires intubation and mechanical ventilation; and 7 requires ventilation and additional organ support including vasopressors, renal replacement therapy and ECMO. A score of 8 is death. Higher levels of CRP, IL-6, IL-10 LDH and TNF-α are associated with higher WHO COVID-19 severity scores.

Fig. 2

CRP, IL-6, IL-10, LDH and TNF- α levels predict the requirement for mechanical ventilation and intensive care. A) Split by four categories of respiratory support (none; supplemental oxygen; continuous positive airway pressure (CPAP); and mechanical ventilation. One way ANOVA shows these four categories are significantly different for CRP, IL-6, IL-10, LDH and TNF- α. B) Receiver operator characteristic curves of CRP, IL-6, IL-10, LDH and TNF- α demonstrating the area under the curve (AUC) for predicting the requirement for intensive care.