In the lungs, fibrosis is a growing clinical problem that results in shortness of breath and can end up in respiratory failure. Even though the main fibrotic disease affecting the lung is idiopathic pulmonary fibrosis (IPF), which affects the interstitial space, there are many fibrotic events that have high and dangerous consequences for the lungs. Asthma, chronic obstructive pulmonary disease (COPD), excessive allergies, clearance of infection or COVID-19, all are frequent diseases that show lung fibrosis. In this review, we describe the different kinds of fibrosis and analyse the main types of cells involved—myofibroblasts and other cells, like macrophages—and review the main fibrotic mechanisms. Finally, we analyse present treatments for fibrosis in the lungs and highlight potential targets for anti-fibrotic therapies.

Background: The coronavirus disease (COVID-19) pandemic has already affected more than 400 million people, with increasing numbers of survivors. These data indicate that a myriad of people may be affected by pulmonary sequelae of the infection. The aim of this study was to evaluate pulmonary sequelae in patients with bilateral COVID-19 pneumonia according to severity 1 year after hospital discharge. Methods: COVID-FIBROTIC is a multicenter prospective observational cohort study for admitted patients with bilateral COVID-19 pneumonia. Pulmonary functional outcomes and chest computed tomography sequelae were analyzed 12 months after hospital discharge and we classified patients into three groups according to severity. A post hoc analysis model was designed to establish how functional test changed between groups and over time. A multivariable logistic regression model was created to study prognostic factors for lung diffusion impairment and radiological fibrotic-like changes at 12 months. Results: Among 488 hospitalized patients with COVID-19 pneumonia, 284 patients had completed the entire evaluation at 12 months. Median age was 60.5 ± 11.9 and 55.3% were men. We found between-group differences in male sex, length of hospital stay, radiological involvement and inflammatory laboratory parameters. The functional evaluation of pulmonary sequelae showed that severe patients had statistically worse levels of lung diffusion at 2 months but no between group differences were found in subsequent controls. At 12-month follow up, however, we found impaired lung diffusion in 39.8% unrelated to severity. Radiological fibrotic-like changes at 12 months were reported in 22.7% of patients (102/448), only associated with radiological involvement at admission (OR: 1.55, 95% CI 1.06–2.38; p = 0.02) and LDH (OR: 0.99, 95% CI 0.98–0.99; p = 0.046). Conclusion: Our data suggest that a significant percentage of individuals would develop pulmonary sequelae after COVID 19 pneumonia, regardless of severity of the acute process. Trial registration clinicaltrials.gov NCT04409275 (June 1, 2020)

Beyond the acute infection of coronavirus disease (COVID-19), concern has arisen about long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of our study was to analyze if there is any biomarker of fibrogenesis in patients with COVID-19 pneumonia capable of predicting post-COVID-19 pulmonary sequelae. We conducted a multicenter, prospective, observational cohort study of patients admitted to a hospital with bilateral COVID-19 pneumonia. We classified patients into two groups according to severity, and blood sampling to measure matrix metalloproteinase 1 (MMP-1), MMP-7, periostin, and VEGF and respiratory function tests and high-resolution computed tomography were performed at 2 and 12 months after hospital discharge. A total of 135 patients were evaluated at 12 months. Their median age was 61 (interquartile range, 19) years, and 58.5% were men. We found between-group differences in age, radiological involvement, length of hospital stay, and inflammatory laboratory parameters. Differences were found between 2 and 12 months in all functional tests, including improvements in predicted forced vital capacity (98.0% vs. 103.9%; P = 0.001) and Dl CO <80% (60.9% vs. 39.7%; P = 0.001). At 12 months, 63% of patients had complete high-resolution computed tomography resolution, but fibrotic changes persisted in 29.4%. Biomarker analysis demonstrated differences at 2 months in periostin (0.8893 vs. 1.437 ng/ml; P < 0.001) and MMP-7 (8.7249 vs. 15.2181 ng/ml; P < 0.001). No differences were found at 12 months. In multivariable analysis, only 2-month periostin was associated with 12-month fibrotic changes (odds ratio, 1.0013; 95% confidence interval, 1.0006–1.00231; P = 0.003) and 12-month Dl CO impairment (odds ratio, 1.0006; 95% confidence interval, 1.0000–1.0013; P = 0.047). Our data suggest that early periostin postdischarge could predict the presence of fibrotic pulmonary changes.

Background: Heart disease is linked to worse acute outcomes after coronavirus disease 2019 (COVID-19), although long-term outcomes and prognostic factor data are lacking. We aim to characterize the outcomes and the impact of underlying heart diseases after surviving COVID-19 hospitalization. Methods: We conducted an analysis of the prospective registry HOPE-2 (Health Outcome Predictive Evaluation for COVID-19-2, NCT04778020). We selected patients discharged alive and considered the primary end-point all-cause mortality during follow-up. As secondary main end-points, we included any readmission or any post-COVID-19 symptom. Clinical features and follow-up events are compared between those with and without cardiovascular disease. Factors with p < 0.05 in the univariate analysis were entered into the multivariate analysis to determine independent prognostic factors. Results: HOPE-2 closed on 31 December 2021, with 9299 patients hospitalized with COVID-19, and 1805 died during this acute phase. Finally, 7014 patients with heart disease data were included in the present analysis, from 56 centers in 8 countries. Heart disease (+) patients were older (73 vs. 58 years old), more frequently male (63 vs. 56%), had more comorbidities than their counterparts, and suffered more frequently from post-COVID-19 complications and higher mortality (OR _{heart disease}: 2.63, 95% CI: 1.81–3.84). Vaccination was found to be an independent protector factor (HR _{all-cause death}: 0.09; 95% CI: 0.04–0.19). Conclusions: After surviving the acute phase, patients with underlying heart disease continue to present a more complex clinical profile and worse outcomes including increased mortality. The COVID-19 vaccine could benefit survival in patients with heart disease during follow-up.