The Role of Cytokines and Molecular Pathways in Lung Fibrosis Following SARS-CoV-2 Infection: A Physiopathologic (Re)view

• Published in: Biomedicines 2024-03, Vol.12 (3), p.639
• Main Authors: Lazar, Mihai, Sandulescu, Mihai, Barbu, Ecaterina Constanta, Chitu-Tisu, Cristina Emilia, Andreescu, Darie Ioan, Anton, Andreea Nicoleta, Erculescu, Teodora Maria, Petre, Alexandru Mihai, Duca, George Theodor, Simion, Vladimir, Padiu, Isabela Felicia, Pacurar, Cosmina Georgiana, Rosca, Ruxandra, Simian, Teodor Mihai, Oprea, Constantin Adrian, Ion, Daniela Adriana
• Format: Article
• Language: English
• Subjects: Alveoli; Chronic illnesses; Collagen; COVID-19; Cytokines; Cytomegalovirus; Development and progression; Epstein-Barr virus; Extracellular matrix; Fibroblasts; Fibrosis; fibrosis mediators; fibrosis predictors; Health aspects; HIV; Human immunodeficiency virus; Hypoxemia; Infection; Infections; Influenza; Interleukins; Legumain; Leukocytes (neutrophilic); long COVID-19; Lung diseases; lung fibrosis; Lungs; Macrophages; Medical research; Medicine, Experimental; Osteopontin; Pathogenesis; Platelet-derived growth factor; Pulmonary fibrosis; Review; Risk factors; SARS-CoV-2 infection; Severe acute respiratory syndrome coronavirus 2; Tomography; Transforming growth factor-b; Transforming growth factors; Tumor necrosis factor-α; Ventilation; Viral infections
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines12030639

SARS-CoV-2 infection is a significant health concern that needs to be addressed not only during the initial phase of infection but also after hospitalization. This is the consequence of the various pathologies associated with long COVID-19, which are still being studied and researched. Lung fibrosis is an important complication after COVID-19, found in up to 71% of patients after discharge. Our research is based on scientific articles indexed in PubMed; in the selection process, we used the following keywords: "lung fibrosis", "fibrosis mediators", "fibrosis predictors", "COVID-19", "SARS-CoV-2 infection", and "long COVID-19". In this narrative review, we aimed to discuss the current understanding of the mechanisms of initiation and progression of post-COVID-19 lung fibrosis (PC-19-LF) and the risk factors for its occurrence. The pathogenesis of pulmonary fibrosis involves various mediators such as TGF-β, legumain, osteopontin, IL-4, IL-6, IL-13, IL-17, TNF-α, Gal-1, Gal-3, PDGF, and FGFR-1. The key cellular effectors involved in COVID-19 lung fibrosis are macrophages, epithelial alveolar cells, neutrophils, and fibroblasts. The main fibrosis pathways in SARS-CoV-2 infection include hypoxemia-induced fibrosis, macrophage-induced fibrosis, and viral-fibroblast interaction-induced fibrosis.