Rationale: The diagnostic concordance between transbronchial lung cryobiopsy (TBLC)—versus surgical lung biopsy (SLB) as the current gold standard—in interstitial lung disease (ILD) cases requiring histology remains controversial. Objectives: To assess diagnostic concordance between TBLC and SLB sequentially performed in the same patients, the diagnostic yield of both techniques, and subsequent changes in multidisciplinary assessment (MDA) decisions. Methods: A two-center prospective study included patients with ILD with a nondefinite usual interstitial pneumonia pattern (on high-resolution computed tomography scan) confirmed at a first MDA. Patients underwent TBLC immediately followed by video-assisted thoracoscopy for SLB at the same anatomical locations. After open reading of both sample types by local pathologists and final diagnosis at a second MDA (MDA2), anonymized TBLC and SLB slides were blindly assessed by an external expert pathologist (T.V.C.). Kappa-concordance coefficients and percentage agreement were computed for: TBLC versus SLB, MDA2 versus TBLC, MDA2 versus SLB, and blinded pathology versus routine pathology. Measurements and Main Results: Twenty-one patients were included. The median TBLC biopsy size (longest axis) was 7 mm (interquartile range, 5–8 mm). SLB biopsy sizes averaged 46.1 ± 13.8 mm. Concordance coefficients and percentage agreement were: TBLC versus SLB: κ = 0.22 (95% confidence interval [CI], 0.01–0.44), percentage agreement = 38% (95% CI, 18–62%); MDA2 versus TBLC: κ = 0.31 (95% CI, 0.06–0.56), percentage agreement = 48% (95% CI, 26–70)%; MDA2 versus SLB: κ = 0.51 (95% CI, 0.27–0.75), percentage agreement = 62% (95% CI, 38–82%); two pneumothoraces (9.5%) were recorded during TBLC. TBLC would have led to a different treatment if SLB was not performed in 11 of 21 (52%) of cases. Conclusions: Pathological results from TBLC and SLB were poorly concordant in the assessment of ILD. SLBs were more frequently concordant with the final diagnosis retained at MDA.

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.

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 (CT_H). Three months after being discharged, these patients were evaluated by a clinical examination, pulmonary function tests and a chest-CT scan (CT_FU). 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 CT_H. 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 CT_FU 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.

Background: In hospitalized patients with COVID-19 pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for ICU and mortality. Methods: We conducted a multicenter, observational study to explore the association between exposure to prolonged, low-dose, MP treatment and need for ICU referral, intubation or death within 28 days (composite primary endpoint) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. Results: Findings are reported as MP (n=83) vs. control (n=90). The composite primary endpoint was met by 19 vs. 40 [adjusted hazard ratio (HR) 0.41; 95% confidence interval (CI): 0.24-0.72]. Transfer to ICU and need for invasive MV was necessary in 15 vs. 27 (p=0.07) and 14 vs. 26 (p=0.10), respectively. By day 28, the MP group had fewer deaths (6 vs. 21, adjusted HR=0.29; 95% CI: 0.12-0.73) and more days off invasive MV (24.0 ± 9.0 vs. 17.5 ± 12.8; p=0.001). Study treatment was associated with rapid improvement in PaO ₂ :FiO ₂ and CRP levels. The complication rate was similar for the two groups (p=0.84). Conclusion: In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Randomized controlled studies are needed to confirm these findings. Registration: ClinicalTrials.gov. Identifier: NCT04323592

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality.