Biomarkers and Prognostic Factors in COVID-19 Severity

Severe COVID-19 arises from a complex interplay of viral replication, dysregulated immune responses and endotheliopathy. Biomarkers have proved crucial for stratifying patients at risk of respiratory failure, thrombo-inflammation and multiorgan injury. Circulating mediators of hyperinflammation—such as C-reactive protein and interleukins—anticoagulant and endothelial markers like mid-regional pro-adrenomedullin, and proteases involved in tissue turnover including matrix metalloproteinases have each been investigated. Composite signatures reflecting cytokine storm, extracellular matrix remodelling and endothelial dysfunction enable more precise prognostication and guide therapeutic intervention. Emerging studies also highlight the value of novel markers such as soluble urokinase plasminogen activator receptor and extracellular matrix glycoproteins in predicting acute kidney injury, fibrotic sequelae and mortality. Integration of these biomarkers into clinical algorithms has underpinned global efforts to triage patients, tailor anti-inflammatory therapy and inform post-acute care, thereby reducing COVID-19 mortality and long-term morbidity.

Research from Nature Portfolio

Investigations of matrix metalloproteinases have shed light on early lung injury and subsequent repair in severe COVID-19. Serum levels of MMP3 rose in direct proportion to initial disease stage, signalling early inflammatory lung damage, whereas MMP9 surged later, reflecting tissue remodelling and repair. This temporal profile offers a dual biomarker approach to capture distinct phases of pulmonary pathology. Parallel studies of mid-regional pro-adrenomedullin at hospital admission demonstrated its strong association with progression to critical illness and death. Threshold values above 1.8 nmol L−1 reliably identified patients requiring intubation or intensive care. Combining clinical scores with MR-proADM measurements has improved risk stratification and informed escalation of care.

Biomarkers and Prognostic Factors in COVID-19 Severity publication trend

The graph below shows the total number of articles in biomarkers and prognostic factors in covid-19 severity across all publications each year (not limited to Nature Index journals).

Technical terms

Biomarker: a measurable substance in tissues or fluids that indicates normal or pathogenic processes, or responses to treatment.

Prognostic factor: a clinical or biological characteristic that provides information on likely disease progression independent of treatment.

Extracellular matrix remodelling: the dynamic alteration of structural proteins and glycoproteins in tissues during injury and repair.

Matrix metalloproteinases (MMPs): a family of zinc-dependent enzymes that degrade extracellular matrix components and regulate inflammation and fibrosis.

Mid-regional pro-adrenomedullin (MR-proADM): a stable fragment of the adrenomedullin precursor peptide used as a marker of endothelial function and severity in systemic illness.

Soluble urokinase plasminogen activator receptor (suPAR): a circulating form of uPAR reflecting immune activation, inflammation and risk of organ dysfunction.

Cytokine storm: an excessive, uncontrolled release of pro-inflammatory cytokines leading to tissue damage and organ failure.

References

1. Circulating markers of extracellular matrix remodelling in severe COVID‐19 patients. Journal of Internal Medicine (2023).
2. Comparison of C-reactive protein with distinct hyperinflammatory biomarkers in association with COVID-19 severity, mortality and SARS-CoV-2 variants. Frontiers in Immunology (2023).
3. Circulating Soluble Urokinase Plasminogen Activator Receptor as a Predictive Indicator for COVID-19-Associated Acute Kidney Injury and Mortality: Clinical and Bioinformatics Analysis. International Journal of Molecular Sciences (2023).
4. Matrix metalloproteinases (MMP) 3 and 9 as biomarkers of severity in COVID-19 patients. Scientific Reports (2022).
5. MR-proADM as prognostic factor of outcome in COVID-19 patients. Scientific Reports (2021).