REVIEW ON IMMUNOPATHOPHYSIOLOGY AND INFLAMMATORY BIOMARKERS IN SEVERE COVID-19. FROM MECHANISMS TO CLINICAL APPLICATIONS
DOI:
https://doi.org/10.52692/1857-0011.2025.2-82.33Keywords:
COVID-19, inflammatory biomarkers, chemokine, ARDS, immune dysregulation, tocilizumabAbstract
Introduction. Severe COVID-19 cases are characterized by a complex interaction involving viral-induced cellular damage, immune system imbalances, endothelial impairment, and inflammation-driven blood clotting. This article provides a comprehensive overview of the key pathophysiological mechanisms, it underscores the critical importance of inflammatory biomarkers in the diagnostic process, prognostic stratification, and therapeutic guidance. Understanding the relationship between these mechanisms and specific biomarkers facilitates a more personalized approach to managing critically ill patients with COVID-19. Aim og the article. The aim of this article is to provide a comprehensive and up-to-date review of the immune- related pathophysiological mechanisms underlying severe forms of COVID-19, with a particular focus on the diagnostic, prognostic, and therapeutic relevance of inflammatory biomarkers. By integrating recent clinical and molecular evidence, the paper seeks to highlight how these biomarkers can support early risk stratification and guide personalized therapeutic strategies, ultimately contributing to improved outcomes in critically ill patients. Material and Methods. The review was carried out through a systematic and extensive search of the specialized literature published between January 2020 and May 2025, using relevant databases (PubMed, Scopus, Web of Science, Google Scholar). Search terms such as: “severe COVID-19”, “inflammatory biomarkers”, “cytokine storm”, “immune dysregulation”, “CRP”, “IL-6”, “TNF-α”, “ferritin”, “D-dimer”, “RAAS”, “ARDS”, “NETs”, “endothelial dysfunction” were included. The included studies were selected based on the criteria of quality, thematic relevance, methodological validity and clinical applicability. Non-scientific articles, pediatric cases, commentaries and papers published in languages other than English were excluded. The selected articles were grouped by major themes: pathogenesis, biomarker classification, clinical utility and prognostic value.Results. The results of the analysis highlight that the severity of COVID-19 is determined by a complex interaction between endothelial dysfunction, excessive immune activation, RAAS imbalance and hypercoagulability. These mechanisms lead to systemic inflammation, immunothrombosis and multisystemic damage, especially pulmonary, renal, cardiac and neurological. The identified biomarkers - such as IL-6, CRP, D-dimer, TNF-α, ferritin and CXCL10 - reflect these processes and allow a dynamic assessment of the severity of the disease. Clinical studies have demonstrated that increased levels of these markers correlate with high mortality and variable therapeutic response. The use of biomarkers in guiding immunotherapy has shown significant benefits in prognosis and individualization of treatment.
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