TGF-β and CCL18 as Indicators for Predicting and Monitoring the Development of Pulmonary Fibrosis in Patients with COVID-19

Abstract

BackgroundMany COVID-19 patients have been discharged, but lung injury, including pulmonary fibrosis, might lead to long-term impairment. This study aimed to evaluate predictors and monitors of pulmonary fibrosis in patients with COVID-19.MethodsThirty-five convalescent patients with severe COVID-19, after appropriate medical treatments, were recruited. According to evidence of fibrosis on initial computed tomography (CT), the patients were divided into mild-to-moderate and severe groups. Levels of transforming growth factor beta (TGF-β), chemokine ligand 18 (CCL18), type III procollagen peptide (PⅢP), hyaluronic acid (HA), laminin (LN), and type IV collagen (CⅣ) were determined. Laboratory tests, clinical data, and CT features at different stages were collected and analyzed, and the prognostic performance of these parameters was evaluated.ResultsSevere fibrosis was found in 76.29% (26/35) of patients. However, most baseline laboratory characteristics were normal. Fibrosis indicators (TGF-β: 66.67±158.57 vs 55.84±126.43 pg/mL, P=0.006; CCL18: 364.27±167.70 vs 84.47±60.67 ng/mL, P=0.000; PⅢP: 54.12±55.34 vs 17.15±2.48 ng/mL, P=0.000; HA: 122.47±78.84 vs 59.74±18.01 ng/mL, p=0.000; LN: 55.43±46.44 vs 24.25±7.79 ng/mL, P=0.000; CⅣ: 24.77±14.97 vs 15.32±1.15 ng/mL, P=0.001) were elevated in patients compared with controls. Over 90 days’ follow-up, HRCT scores gradually decreased from 22.48±16.13 to 10.33±11.11 (P<0.001), and mMRC scores decreased from 3.27±0.32 to 1.48±0.33, and all fibrosis indicators, except for PⅢP, gradually declined with the improvement of pulmonary fibrosis. Moreover, TGF-β and CCL18 levels were lower in the mild-to-moderate than severe fibrosis group (88.16±97.45 vs 205.93±170.57 pg/mL, P=0.024; 241.84±125.37 vs 366.64±161.06 ng/mL, P=0.038), and patients with elevated baseline levels of serum TGF-β and CCL18 had longer rehabilitation times.ConclusionsTGF-β and CCL18 may be promising biomarkers for predicting and monitoring the development of pulmonary fibrosis in patients with COVID-19.

Local CCL18 and CCL21 expand lung fibrovascular niches and recruit lymphocytes, leading to tertiary lymphoid structure formation in prolonged COVID-19

“…3A). It remains to be evaluated whether the reported systemic increase in CCL18 during COVID-19 38 is associated with fibrosis in other tissues beyond the lung, and whether increased CCL18 serum levels are associated to Long-COVID.…”