ABSTRACT
Background: Coronavirus disease-19 (COVID-19) is an infectious disease that can result in serious respiratory illness. It is associated with extensive systemic inflammation and changes to the lung extracellular matrix (ECM), which may result in diffuse alveolar damage and pulmonary fibrosis. In this study, the aim was to investigate whether ECM remodeling, wound healing, and neutrophil activity is altered in patients with COVID-19, with or without interstitial lung disease (ILD). Method(s): Serum was collected from 72 patients with COVID-19 infection 3 months after diagnosis, 10 of whom developed ILD, and from 16 healthy controls. A panel of neo-epitope specific ELISAs reflecting type III collagen crosslinking (PC3X), type III and VI collagen formation (PRO-C3 and PRO-C6), type I, III, and VI collagen degradation (C1M, C3M, and C6M), fibrin crosslinking (X-FIB), fibrin clot formation (PRO-FIB), elastin degradation (EL-NE and ELP-3), and calprotectin degradation (CPa9-HNE) were assessed in serum of patients. Result(s): Mean serum neo-epitopes PC3X (p<0.0001), PRO-C3 (p=0.0024), C3M (p=0.0085), PRO-FIB (p<0.0001), ELP-3 (p<0.0001), and CPa9-HNE (p<0.0001) were significantly elevated in patients with COVID-19 compared to healthy controls. Additionally, PC3X (p=0.023) and PRO-C3 (p=0.0317) were significantly elevated in COVID-19 patients who developed ILD when compared to those who did not. Conclusion(s): Non-invasive serological biomarkers reflecting tissue remodeling were significantly elevated in patients infected with COVID-19. Additionally, type III collagen crosslinking and formation may differentiate patients who develop ILD consequent to COVID-19 infection.
ABSTRACT
Pulmonary fibrosis has been identified as a main factor leading to pulmonary dysfunction and poor quality of life in post-recovery Severe Acute Respiratory Syndrome (SARS) survivor's consequent to SARS-Cov-2 infection. Thus there is an urgent medical need for identification of readily available biomarkers that in patients with SARS-Cov-2 infection are able to; (1) identify patients in most need of medical care prior to admittance to an intensive care unit (ICU), and; (2) identify patients post-infection at risk of developing persistent fibrosis of lungs with subsequent impaired quality of life and increased morbidity and mortality. An intense amount of research have focused on wound healing and Extracellular Matrix (ECM) remodelling of the lungs related to lung function decline in pulmonary fibrosis (PF). A range of non-invasive serological biomarkers, reflecting tissue remodelling, and fibrosis have been shown to predict risk of acute exacerbations, lung function decline and mortality in PF and other interstitial lung diseases (Sand et al. in Respir Res 19:82, 2018). We suggest that lessons learned from such PF studies of the pathological processes leading to lung function decline could be used to better identify patients infected with SARS-Co-V2 at most risk of acute deterioration or persistent fibrotic damage of the lung and could consequently be used to guide treatment decisions.