Methods: in this retrospective study, we evaluated 394 patients from march 2020 to december 2020 and we enrolled 43 patients who developed fibrotic lesions after 1 year from a sars cov2 pneumoniae. These patients underwent BAL (Bronchioloalveolar lavage), respiratory functional and immunological tests. At admission, 41/43 patients had GGO on chest CT scan, while 13/43 showed parenchymal consolidation. 9/43 were treated with oxygen therapy, 14/43 with HNFC, 10/43 with NIV, 10/43 with IOT. At 12 months CT, 23/43 had persistent GGO areas and 2/43 lung consolidations. All showed new onset interstitial thickening. Results: no differences in lung volumes between patients who required mechanical ventilation vs those who did not; while the Dlco values were lower in mechanical ventilated patients (p=0.047). The median negativization of the nasopharyngeal molecular swab was 30 days: we didn9t show differences in either inflammation markers and in the respiratory function parameters in those who had negativization before or after 30 days. 43/394 patients showed persistence of DLco and CT scan alterations. We submitted these patients to BAL in order to quantify whether there was inflammation of the lung. Median lymphocytes on BAL was 10%, while median serum lymphocytes was 31.4%. Only 4/43 patients had BAL lymphocytosis greater than 30%. We treated these 4 patients with systemic steroid therapy as an organizing pneumoniae. Conclusion: patients who were hospitalized with respiratory failure due to Covid 19, 10% had TC and respiratory functional changes after one year and 10% of these, had lymphocytic inflammation in the BAL, treated with steroid. Further studies are needed.

Background Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and other Rheumatic Diseases, and is one of the major causes of mortality. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and anti-inflammatory effects in preclinical models of systemic sclerosis and ILD. Objectives To evaluate efficacy and safety of Nintedanib in pulmonary fibrosis secondary to Connective Tissue Disease. Methods Ten patients with pulmonary fibrosis secondary to Connective Tissue Disease treated with Nintedanib were monitored at baseline, 6 and/or 12 months, with clinical assessment, chest CT scan and/or pulmonary function testing (PFT) with assessment of the diffusing capacity for CO (DLCO). 8/10 patients had a diagnosis of Progressive Systemic Sclerosis, while the remaining ones had Polydermatomyositis and Mixed Connectivitis. All patients were dyspnoic at baseline and presented with dry cough. All patients had pulmonary fibrosis according to high-resolution chest CT scan. All patients had been treated with at least one csDMARD or bDMARD (cyclophosphamide, azathioprine, cyclosporine, rituximab, tocilizumab), prior to receiving nintedanib. At baseline 2/10 patients were treated with Nintedanib monotherapy, 7/10 were in combination therapy with Mycophenolate, 1 patient received a combination therapy with cyclosporine. Results Compared to baseline values, 4/7 patients showed stationarity of the respiratory function parameters (DLCO), in 2/7 patients it was observed a significant improvement of the DLCO (with a change of 15%) while in only 1 patient there was a worsening over time. FVC remained stable over time except in 1 patient who got a significant improvement. In 5/9 patients cough improved (unchanged in the rest of patients). Dyspnea (NYHA scale) improved in 6/9 patients, remained stationary in 2/6 patients and became worse in 1 patient. 8/9 patients had a stable chest CT at 6 and / or 12 months, while only 1 patient witnessed a further worsening of the fibrosis. 50% of the patients showed good gastrointestinal tolerance to the full dose of nintedaninb. The other half had the dose reduced in order to improve gastrointestinal symptoms. Conclusion Our data show that patients with ILD associated with Rheumatic Diseases treated with nintedanib had a clinical benefit over dyspnea and cough symptoms and a stabilization of radiological findings 12 months after starting the treatment. Also, respiratory function parameters remained stable over time. Gastrointestinal adverse events, including diarrhea, were common in these patients, but therapeutic dose adjustment led to fast symptoms resolution and good tolerance. References [1]Kristin B Highland, Oliver Distler, Masataka Kuwana, Yannick Allanore, Shervin Assassi, Arata Azuma, Arnaud Bourdin, Christopher P Denton, Jörg H W Distler, Anna Maria Hoffmann-Vold, Dinesh Khanna, Maureen D Mayes, Ganesh Raghu, Madelon C Vonk, Martina Gahlemann, Emmanuelle Clerisme-Beaty, Mannaig Girard, Susanne Stowasser, Donald Zoz, Toby M Maher, SENSCIS trial investigators. Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease treated with mycophenolate: a subgroup analysis of the SENSCIS trial. Lancet Respir Med. 2021 Jan;9(1):96-106. [2]Oliver Distler, Kristin B Highland, Martina Gahlemann, Arata Azuma, Aryeh Fischer, Maureen D Mayes, Ganesh Raghu, Wiebke Sauter, Mannaig Girard, Margarida Alves, Emmanuelle Clerisme-Beaty, Susanne Stowasser, Kay Tetzlaff, Masataka Kuwana, Toby M Maher, SENSCIS Trial Investigators. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med. 2019 Jun 27;380(26):2518-2528. Disclosure of Interests None declared

At present, the time-frame used for the quarantine of individuals with coronavirus disease 2019 (COVID-19) is the entire duration of symptoms plus 14 days after symptom recovery; however, no data have been reported specifically for healthcare workers (HCWs). In the study population of 142 HCWs with COVID-19, the mean time for viral clearance was 31.8 days. Asymptomatic subjects cleared the virus more quickly than symptomatic subjects (22 vs 34.2 days; P<0.0001). The presence of fever at the time of diagnosis was associated with a longer time to viral clearance (relative risk 11.45, 95% confidence interval 8.66–14.25; P<0.0001). These findings may have a significant impact on healthcare strategies for the future management of the COVID-19 pandemic.

Recent reports provided an evidence of some clinical efficacy for extracorporeal photopheresis in improving/stabilizing graft function in nearly 60% of treated BOS patients (overall 49 BOS pts reported). The purpose of this study was to evaluate clinical and immunological effects of ECP in a cohort of lung recipients with macrolide non-responsive BOS: 8 with BOS grade 1, 6 with BOS 2, 2 with BOS 3.

Respiratory viral infections are responsable of a significant morbidity in LTRs and have been considered a possible risk factor for chronic lung function decline. Aim of our study was to asses the incidence of viral respiratory infections in a cohort of 17 LTRs in the first post transplant year, and correlate BAL samples and naso-pharingeal secretions (NPS) findings with clinical, functional, and radiological data. A total of 84 BAL samples and 16 NPS were analysed with direct immunofluorescence, shell vial cultures, and molecular assays. The incidence of respiratory viral infection was 0.94 episodes per patient/year. In all a total of 16 isolates were collected from 10 LTR: 5 from NPS and and 11 from BAL: Rhinovirus (1 NPS, 4 BAL); Respiratory Syncytial Virus (2 NPS, 1 BAL), Metapneumovirus (1 NPS); Parainfluenza virus (1 BAL), human Coronavirus 229E (1 NPS) and OC43 (2 BAL), Herpesviruses (3 BAL). Nine of these 16 episodes were associated to respiratory symptoms (dyspnoea, cough, faringodynia, coriza) functional impairment (4 cases) and/or radiological signs (bibasilar infiltrates, ground glass alterations, small centrilobular opacities, pleural effusion). In addition, 4 pulmonary CMV infections were detected defined as a presence of CMV DNA > 100.000 copies/ml of BAL fluids in absence of radiological and clinical signs. CMV infections were treated with a 21 days course of i.v. gancyclovir while RSV infections were treated with nebulized ribavirin. In all other episodes only symptomatic treatment was performed with complete remission within 2 weeks. The incidence of respiratory viral infection during the first post-transplant year was relatively high, however did not persistently affect graft function in this small cohort of LTRs.

CD4+CD25+ regulatory T (Treg) cells have been shown to play a role in allograft tolerance and their peripheral counts vary according to the degree of graft acceptance in lung transplant recipients (LTR). Recent studies demonstrate that certain drugs might modulate generation, expansion and activity of Treg cells. Aim of this study was to evaluate the effect of therapeutic regimens used in our institution on peripheral CD4+CD25highCD69− Treg cell numbers in a group of 51 LTR with stable clinical conditions. They were treated with standard immunosuppression: calcineurin inhibitor (CNI) + azathioprine (AZA) + steroids (n = 28) or with CNI + mycophenolate mofetil (MMF) + steroids (n = 11) or with CNI + steroids (n = 12). These stable LTR were compared with age-matched healthy controls (n = 35) and with 19 LTR who developed bronchiolitis obliterans syndrome (BOS) and were treated analogously. Stable LTR showed higher peripheral Treg cell counts with respect to age-matched healthy controls (59.9 ± 31.8/μl versus 42.1 ± 16.9/μl, respectively; p < 0.05). This increase was detectable in all patients treated with CNI either in association with AZA or MMF. During these treatments a significant expansion of Treg cell counts was detectable during acute rejection (AR) episodes (86.03 ± 26.6/μl during AR versus 36.34 ± 7.6 before AR; p < 0,05). Moreover, the development of BOS was associated to a significant decrease of Treg cell counts irrespective to the immunosuppressive regimen used. In conclusion, therapeutic regimens based on CNI seem to allow a certain degree of peripheral Treg cell expansion in stable LTR.