COVID-19 Biomarkers at the Crossroad between Patient Stratification and Targeted Therapy: The Role of Validated and Proposed Parameters

Abstract

Clinical knowledge about SARS-CoV-2 infection mechanisms and COVID-19 pathophysiology have enormously increased during the pandemic. Nevertheless, because of the great heterogeneity of disease manifestations, a precise patient stratification at admission is still difficult, thus rendering a rational allocation of limited medical resources as well as a tailored therapeutic approach challenging. To date, many hematologic biomarkers have been validated to support the early triage of SARS-CoV-2-positive patients and to monitor their disease progression. Among them, some indices have proven to be not only predictive parameters, but also direct or indirect pharmacological targets, thus allowing for a more tailored approach to single-patient symptoms, especially in those with severe progressive disease. While many blood test-derived parameters quickly entered routine clinical practice, other circulating biomarkers have been proposed by several researchers who have investigated their reliability in specific patient cohorts. Despite their usefulness in specific contexts as well as their potential interest as therapeutic targets, such experimental markers have not been implemented in routine clinical practice, mainly due to their higher costs and low availability in general hospital settings. This narrative review will present an overview of the most commonly adopted biomarkers in clinical practice and of the most promising ones emerging from specific population studies. Considering that each of the validated markers reflects a specific aspect of COVID-19 evolution, embedding new highly informative markers into routine clinical testing could help not only in early patient stratification, but also in guiding a timely and tailored method of therapeutic intervention.

Keywords: C-reactive protein (CRP); COVID-19; D-dimer; IFN-inducible protein 10 (IP10); SARS-CoV-2 viremia; biomarkers; calcitonin gene-related peptide (CGRP); ferritin; growth arrest-specific gene 6 (Gas6); interleukin 6 (IL6); neutrophil-to-lymphocyte ratio (NLR); osteopontin (OPN); red cell distribution width (RDW).

Figure 1

Summary of the most clinically used biomarker (RDW, D-dimer, ferritin, NLR, CRP, and IL6) trajectories in predicting COVID-19 disease evolution.

Figure 2

Summary of the most promising biomarker (IP10, Gas6, RNAemia, osteopontin, and CGRP) trajectories in predicting COVID-19 disease evolution.