The role of transforming growth factor β in COVID-19 lung injury: clinical and diagnostic parallels

Abstract

BACKGROUND: Severe acute respiratory syndrome causes complex immune responses of hyperactivation of immunocompetent cells, including increased degranulation activity of mast cells and release of their secretome products. Mast cell granules may contain a lot of profibrotic enzymes and cytokines (chymase, tryptase, interleukin-4, 10, and 13) as well as growth factors. The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the body and the subsequent strong immune and inflammatory response and dysregulation of coagulation and fibrinolytic pathways cause massive activation of latent (inactive) transforming growth factor β (TGF-β) in the lungs and the latent pool of TGF-β in the blood of patients with coronavirus disease 2019 (COVID-19). AIM: To evaluate the role of TGF-β in lung involvement in patients with COVID-19 by examining autopsy lung material, determining the quantitative level of TGF-β with further correlation analysis of clinical and laboratory parameters. MATERIALS AND METHODs: The study included autopsy lung samples from patients who died from severe COVID-19. Autopsies were performed 2 days after the patients died. Autopsy material was collected for histology. Correlation analysis was performed between the number of TGF-β-positive cells and clinical and laboratory parameters. RESULTS: Extensive representation of TGF-β positive cells was found in autopsy tissues. A negative correlation was found between the number of TGF-β-positive cells and the blood concentration of band neutrophils (r=−0.617; p=0.033); between the number of TGF-β-positive cells and the concentration of C-reactive protein according to blood chemistry (r=–0.491; p=0.013). A positive correlation was found between the number of TGF-β-positive cells and blood platelet concentration (r=0.384; p=0.012); the number of TGF-β-positive cells and erythrocyte sedimentation rate (r=0.409; p=0.025). A positive correlation was also found between the number of TGF-β-positive cells and the presence of a cough in the patient at the beginning of the hospital stay (r=0.367; p=0.046). CONCLUSION: A correlation was found between the number of TGF-β-positive cells, neutrophil concentration, platelet concentration, erythrocyte sedimentation rate, C-reactive protein concentration, and the presence of cough in patients who died from severe COVID-19. These correlations suggest the negative role of TGF-β and the therapeutic possibilities of regulating its activation. Further studies in a larger number of patients are required.