Idiopathic pulmonary fibrosis (IPF) is associated with a significantly increased risk of thrombotic events and mortality. This review explores the complex bidirectional relationship between pulmonary fibrosis and thrombosis, discussing epidemiological evidence, pathogenetic mechanisms, and therapeutic implications, with a particular focus on the emerging role of extracellular vesicles (EVs) as crucial mediators linking fibrosis and coagulation. Coagulation factors directly promote fibrosis, while fibrosis itself activates thrombotic pathways. Retrospective studies suggest the benefits of anticoagulants in IPF, but prospective trials have faced challenges. Novel anticoagulants, profibrinolytic therapies, and agents targeting protease-activated receptors (PARs) show promise in preclinical studies and early clinical trials. EVs have emerged as key players in the pathogenesis of interstitial lung diseases (ILDs), serving as vehicles for intercellular communication and contributing to both fibrosis and coagulation. EV-based approaches, such as EV modulation, engineered EVs as drug delivery vehicles, and mesenchymal stem cell-derived EVs, represent promising therapeutic strategies. Ongoing research should focus on optimizing risk–benefit profiles, identifying predictive biomarkers, evaluating combination strategies targeting thrombotic, fibrotic, and inflammatory pathways, and advancing the understanding of EVs in ILDs to develop targeted interventions.

Background: To quantitatively evaluate CT lung abnormalities in COVID-19 survivors from the acute phase to 24-month follow-up. Quantitative CT features as predictors of abnormalities’ persistence were investigated. Methods: Patients who survived COVID-19 were retrospectively enrolled and underwent a chest CT at baseline (T0) and 3 months (T3) after discharge, with pulmonary function tests (PFTs). Patients with residual CT abnormalities repeated the CT at 12 (T12) and 24 (T24) months after discharge. A machine-learning-based software, CALIPER, calculated the CT percentage of the whole lung of normal parenchyma, ground glass (GG), reticulation (Ret), and vascular-related structures (VRSs). Differences (Δ) were calculated between time points. Receiver operating characteristic (ROC) curve analyses were performed to test the baseline parameters as predictors of functional impairment at T3 and of the persistence of CT abnormalities at T12. Results: The cohort included 128 patients at T0, 133 at T3, 61 at T12, and 34 at T24. The GG medians were 8.44%, 0.14%, 0.13% and 0.12% at T0, T3, T12 and T24. The Ret medians were 2.79% at T0 and 0.14% at the following time points. All Δ significantly differed from 0, except between T12 and T24. The GG and VRSs at T0 achieved AUCs of 0.73 as predictors of functional impairment, and area under the curves (AUCs) of 0.71 and 0.72 for the persistence of CT abnormalities at T12. Conclusions: CALIPER accurately quantified the CT changes up to the 24-month follow-up. Resolution mostly occurred at T3, and Ret persisting at T12 was almost unchanged at T24. The baseline parameters were good predictors of functional impairment at T3 and of abnormalities’ persistence at T12.

Background: A few months after the COVID-19 pandemic onset, knowledge of SARS-CoV-2 infection and outcomes and treatments blew up. This paper aimed to evaluate the features of a Tuscany COVID-19 hospitalized cohort and to identify risk factors for COVID-19 severity. Methods: This retrospective observational COVID-19 cohort study (1 March 2020–1 March 2021) was conducted on patients ≥ 18 years old, admitted to Tuscany Hospital, and subjected to follow-up within 12 months after discharge. Patients were enrolled at Pisana, Senese and Careggi University Hospitals, and South East, North West, and Center Local Hospitals. Results: 2888 patients (M = 58.5%, mean age = 66.2 years) were enrolled, of whom 14.3% (N = 413) were admitted to an intensive care unit. Smokers were 25%, and overweight and obese 65%. The most used drugs were corticosteroids, antacids, antibiotics, and antithrombotics, all antiviral drugs, with slight differences between 2020 and 2021. A strong association was found between outcomes of evolution towards critical COVID-19 (non-invasive mechanical ventilation (NIV) and/or admission to intensive care) and smoking (RR = 4.91), ex-smoking (RR = 3.48), overweight (RR = 1.30), obese subjects (RR = 1.62), comorbidities (aRR = 1.38). The alteration of liver enzymes (aspartate aminotransferase, alanine aminotransferase, or gamma-glutamyl transpeptidase) was associated with NIV (aOR = 2.28). Conclusions: Our cohort, characterized by patients with a mean age of 66.2 years, showed 65% of patients were overweight and obese. Smoking/ex-smoking, overweight/obesity, and other comorbidities were associated with COVID-19 adverse outcomes. The findings also demonstrated that alterations in liver enzymes were associated with worse outcomes.

Aim: To characterize clinical, functional, and imaging pulmonary phenotypes, and the evolution of COVID-19 in hospitalized patients. Methods: COVID-19 patients were evaluated at 3 (T3) and 12 months (T12) after discharge from the Pisa University Hospital (March-September 2020). Spirometry, lung volumes, DLCO, and the evolution of COVID-19 pneumonia CT signs (PS) were assessed. Through a latent transition analysis (LTA), based on PS, DLCO, and lung function (PFTs), we assessed COVID-19 cross-sectional phenotypes at T3 and T12 and their longitudinal patterns. Risk factors for longitudinal patterns were evaluated by multinomial logistic regression. Results: Among 307 discharged patients, 57% at T3 and 44.3% at T12 were followed up (62.8% males; mean age 61.1 years). Among patients with complete T12-follow-up, 24.1% at T3 and 21.6% at T12 had impaired DLCO, and 4.4% had a restrictive pattern at both T3 and T12. 48.9% and 18.3% had no PS at T3 and T12, respectively, but 32.8% had persistent PS at T12. LTA found three cross-sectional phenotypes at T3 and T12 (i.e., no PS and normal PFTs; PS and normal PFTs; PS and impaired PFTs), and four longitudinal patterns: 1) persistent no PS and normal PFTs (47.9%); 2) resolution of both PS and PFTs at T12 (15.4%); persistence of PS at T12 (36.7%), with 3) (11%) or without 4) (25.7%) PFTs impairment. The last two patterns were associated with higher age, more comorbidities, and severe acute COVID-19. Conclusions: In the first year of the pandemic, older patients, with more comorbidities and severe acute COVID-19, were those with the worst COVID-19 evolution patterns over 12 months and are those who currently need a very long-term follow-up.