Daily Ards Research Analysis

BACKGROUND: Severe and critical COVID-19 is characterized by pulmonary viral infection with SARS-CoV-2 resulting in local and systemic inflammation. Dexamethasone (DEX) has been shown to improve outcomes in critically ill patients; however, its effect on tissue remodeling, particularly collagen turnover, remains unclear. This study investigated the association between circulating extracellular matrix (ECM) remodeling neo-epitopes and COVID-19 severity, their relationship with mortality, and the effect of DEX on these markers. METHODS: We conducted a multi-center prospective cohort study involving 226 COVID-19 patients: 157 with severe disease admitted to the ward and 69 with critical disease admitted to the ICU. Plasma samples were collected at ICU admission and at discharge or death. Circulating collagen degradation (C3M, C4Ma3, and C6M) and synthesis (PRO-C3, PRO-C4, and PRO-C6) neo-epitopes were measured. Longitudinal analysis of ECM neo-epitope changes during ICU stay and their association with mortality was performed, along with an evaluation of the impact of DEX treatment on these markers. RESULTS: Critically ill patients exhibited higher levels of collagen degradation (reflecting inflammatory driven ECM destruction) (C3M, C6M) and collagen synthesis (strongly related to fibroblast activity) (PRO-C3, PRO-C6) neo-epitopes than severe patients. Increased collagen turnover, measured during ICU stay, was associated with mortality. Non-survivors displayed rising levels of collagen degradation and synthesis markers over time, whereas survivors had stable or declining levels. In non-survivors without DEX treatment, C6M and PRO-C6 levels were significantly increased, whereas these elevations were less pronounced in patients treated with DEX. CONCLUSION: Our findings suggest that elevated collagen turnover is associated with poor outcomes in critically ill COVID-19 patients. DEX treatment appeared to attenuate ECM remodeling, although this effect was not linked to improved survival. Further studies are needed to confirm these observations and better understand the role of ECM remodeling in COVID-19 and the potential therapeutic impact of corticosteroids.

INTRODUCTION: In patients with acute respiratory distress syndrome, mechanical ventilation often leads to ventilation-induced lung injury (VILI), which is attributed to unphysiological lung strain (UPLS) in respiratory dynamics. Platelet endothelial cell adhesion molecule-1 (PECAM-1), a transmembrane receptor, senses mechanical signals. The Src/STAT3 pathway plays a crucial role in the mechanotransduction network, concurrently triggering pyroptosis related inflammatory responses. We hypothesized that the mechanical stretch caused by UPLS can be sensed by PECAM-1 in the lungs, leading to VILI via the Src/STAT3 and pyroptosis pathway. METHODS: A VILI model was established in rats through UPLS. The link between lung strain and VILI as well as the change in the activation of PECAM-1, Src/STAT3, and pyroptosis was firstly being explored. Then, the inhibitors of PECAM-1, Src, STAT3 were adopted respectively, the effect on VILI, inflammation, the Src/STAT3 pathway, and pyroptosis was evaluated. RESULTS: UPLS activated PECAM-1, Src/STAT3 signaling pathway, inflammation, and pyroptosis in the VILI model with rats, whereas inhibition of PECAM-1 or the Src/STAT3 signaling pathway decreased lung injury, inflammatory responses, and pyroptosis. Inhibition of PECAM-1 also reduced activation of the Src/STAT3 signaling pathway. The mechanism was validated with HUVECs exposed to overload mechanical cyclic stretch. CONCLUSIONS: This study suggests that UPLS contributes to VILI by activating the PECAM-1/Src/STAT3 pathway and inducing inflammatory responses as well aspyroptosis.

BACKGROUND: SARS-CoV-2 virus which targets the lung vasculature is supposed to affect both pulmonary and bronchial arteries. This study evaluated the tracheobronchial vascularization density observed with narrow band imaging (NBI) in patients hospitalized for COVID-19 pneumonia. To determine if the observed changes were specific of COVID-19 patients, the procedure was also performed in non-COVID-19 patients. METHODS: Thirty patients included in this monocentric, prospective study underwent videobronchoscopy using both white light and NBI: 10 with a COVID-19 infection, 10 with a non-COVID-19 pulmonary infection and 10 with a peripheral pulmonary nodule. The tracheobronchial vascular density observed through NBI was rated by two blinded pneumologists at three levels (carina, right main bronchus and left main bronchus). RESULTS: When compared to the two other groups, a significant increase of the tracheobronchial vascularization was found in COVID-19 patients. The median tracheobronchial vascularization global score obtained with NBI (out of 15 points) was: 10 [9 - 13] in the COVID-19 group, 5 [4 - 10] in the non-COVID-19 group (p < 0.001) and 6 in the Nodule group [4 - 9] (p = 0.002). Using a weighted Cohen's Kappa coefficient, we observed a good agreement between the two raters for the evaluation of the tracheobronchial vascularization score (κ = 0.75 [0.65-0.83]); p < 0.001). CONCLUSION: Videobronchoscopy with NBI in COVID-19 patients showed diffuse changes in tracheobronchial vascularization. We suggest that such bronchial hypervascularisation with dilated vessels contributes, at least in part, to the intrapulmonary right to left shunt that characterized the COVID-19 related Acute Vascular Distress Syndrome (AVDS).