SARS-CoV-2 may lead to a large spectrum of respiratory manifestations, including pulmonary sequelae. We conducted a single-center longitudinal study of survivors from severe COVID-19 cases who underwent a chest CT during hospitalization (CTH). Three months after being discharged, these patients were evaluated by a clinical examination, pulmonary function tests and a chest-CT scan (CTFU). Sixty-two patients were enrolled. At follow-up, 27% complained of exertional dyspnoea and 12% of cough. Dyspnoeic patients had a lower forced expiratory flow (FEF)25–75 (p = 0.015), while a CT scan (p = 0.016 showed that patients with cough had a higher extent of bronchiectasis. Lung volumes and diffusion of carbon monoxide (DLCO) at follow-up were lower in patients who had been invasively ventilated, which correlated inversely with the length of hospitalization and ground-glass extension at CTH. At follow-up, 14.5% of patients had a complete radiological resolution, while 85.5% presented persistence of ground-glass opacities, and 46.7% showed fibrotic-like alterations. Residual ground-glass at CTFU was related to the length of hospitalization (r = 0.48; p = 0.0002) and to the need for mechanical ventilation or high flow oxygen (p = 0.01) during the acute phase. In conclusion, although patients at three months from discharge showed functional impairment and radiological abnormalities, which correlated with a prolonged hospital stay and need for mechanical ventilation, the persistence of respiratory symptoms was related not to parenchymal but rather to airway sequelae.

Pneumothorax (PNX) and pneumomediastinum (PNM) are potential complications of COVID-19, but their influence on patients’ outcomes remains unclear. The aim of the study was to assess incidence, risk factors, and outcomes of severe COVID-19 complicated with PNX/PNM. Methods: A retrospective multicenter case-control analysis was conducted in COVID-19 patients admitted for respiratory failure in intermediate care units of the Treviso area, Italy, from March 2020 to April 2021. Clinical characteristics and outcomes of patients with and without PNX/PNM were compared. Results: Among 1213 patients, PNX and/or PNM incidence was 4.5%. Among these, 42% had PNX and PNM, 33.5% only PNX, and 24.5% only PNM. COVID-19 patients with PNX/PNM showed higher in-hospital (p = 0.02) and 90-days mortality (p = 0.048), and longer hospitalization length (p = 0.002) than COVID-19 patients without PNX/PNM. At PNX/PNM occurrence, one-third of subjects was not mechanically ventilated, and the respiratory support was similar to the control group. PNX/PNM occurrence was associated with longer symptom length before hospital admission (p = 0.005) and lower levels of blood lymphocytes (p = 0.017). Conclusion: PNX/PNM are complications of COVID-19 associated with a worse prognosis in terms of mortality and length of hospitalization. Although they are more frequent in ventilated patients, they can occur in non-ventilated, suggesting that mechanisms other than barotrauma might contribute to their presentation.

Background: The clinical course of IPF is heterogeneous however it is recognized that patients can have a slow (S) or rapid (R) progression of the disease and that R is related to worse prognosis. Aims: By using a HRCT alveolar score (AS) as an index of alveolar inflammation and an interstitial score (IS) as an index of fibrosis we wanted to investigate: 1) If AS and IS could differentiate S from R at a time close to diagnosis; 2) The behavior of the AS and IS over time; 3)The relation of FVC decline to the progression of AS and IS. Methods: 28 IPF patients (17S, 11R) followed longitudinally with FVC had a HRCT close to diagnosis (HRCT1). 13 of these patients (7S and 6R) had a second HRCT2 after 30±25 months of follow up. Ground glass (AS) and fibrosis (IS) % extension (0-100) were scored in each lobe. HRCT1 and HRCT2 scores were computed, the rate of progression calculated and compared to the FVC change between the interval from HRCT1 to HRCT2. Results: In the 28 patients examined at diagnosis, HRCT1 AS in R (23.4±22%) was higher than in S (8.4±14.1%, p< 0.03) while IS was similar (42.2±21% in R vs 41.1±24% in S). In the 13 patients in whom HRCT2 was available, AS significantly increased in S (5.7±8 to 15.4±17%, p<0.05) and R (22±29 to 30±30%, p<0.05) while IS did not increase significantly. The rate of decline of FVC between HRCT1 and HRCT2 correlated strongly with the combined AS and IS change/month (r=0.80, p<0.005). Conclusion: At diagnosis HRCT AS differentiates R from S progressors. The combination of progressive inflammation (AS) and fibrosis (IS) by HRCT seems to drive the functional decay in IPF.

The clinical course of IPF is heterogeneous and unpredictable, however a rapid decline in FVC and telomere shortening appear to be related to worse prognosis. It has been shown that treatment with Pirfenidone can modify disease progression in the majority of patients. Aims: To investigate whether a different pre-treatment disease progression (FVC decline < or > 10% pred/year) is related to leukocyte telomere length (LTL) and can influence the response to Pirfenidone. Methods: We studied the response to Pirfenidone treatment in 26 patients with IPF who had been followed for 1 year prior the beginning of treatment. According to the decline of % predicted FVC before treatment they were classified as slow (≤10%) or rapid (>10%) progressors. Real-time PCR was used to measure LT length in genomic DNA from peripheral blood leukocytes in patients and in 41 healthy controls. Results: After 1 year on treatment the FVC % predicted decline in rapid progressors (n=9) changed from 19± 2% (absolute value 684±84ml) pre-treatment to 4±2% (162±72ml) (p<0.05). No significant differences in decline were observed in the 17 slow progressors (4±1% vs 4±1% and 223±37 ml vs 149±66ml). LTL in both slow and rapid progressors was shorter than controls (1.02, 0.47-2.3 and 0.93, 0.21-3.6 vs1.8, 0.6-5.0; p=0.005 for both), but it was similar in rapid and slow progressors. Conclusion: One year of Pirfenidone treatment significantly decreases the rate of FVC decline in patients with pre-treatment rapid progression, but not in slow progressors. Telomere length does not appear to influence disease behaviour.