Currently, there are four seasonal coronaviruses associated with relatively mild respiratory tract disease in humans. However, there is also a plethora of animal coronaviruses which have the potential to cross the species border. This regularly results in the emergence of new viruses in humans. In 2002, severe acute respiratory syndrome coronavirus (SARS-CoV) emerged and rapidly disappeared in May 2003. In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a possible threat to humans, but its pandemic potential so far is minimal, as human-to-human transmission is ineffective. The end of 2019 brought us information about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emergence, and the virus rapidly spread in 2020, causing an unprecedented pandemic. At present, studies on the virus are carried out using a surrogate system based on the immortalized simian Vero E6 cell line. This model is convenient for diagnostics, but it has serious limitations and does not allow for understanding of the biology and evolution of the virus. Here, we show that fully differentiated human airway epithelium cultures constitute an excellent model to study infection with the novel human coronavirus SARS-CoV-2. We observed efficient replication of the virus in the tissue, with maximal replication at 2 days postinfection. The virus replicated in ciliated cells and was released apically. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged by the end of 2019 and rapidly spread in 2020. At present, it is of utmost importance to understand the biology of the virus, rapidly assess the treatment potential of existing drugs, and develop new active compounds. While some animal models for such studies are under development, most of the research is carried out in Vero E6 cells. Here, we propose fully differentiated human airway epithelium cultures as a model for studies on SARS-CoV-2.

Performing coronary grafts on aspirin is associated with increased postoperative bleeding but may decrease the long-term hazard of coronary events.

30SARS-CoV-2 emerged by the end of 2019 to rapidly spread in 2020. At present, it is of utmost 31 importance to understand the virus biology and to rapidly assess the potential of existing drugs 32 and develop new active compounds. While some animal models for such studies are under 33 development, most of the research is carried out in the Vero E6 cells. Here, we propose fully 34 differentiated human airway epithelium cultures as a model for studies on the SARS-CoV-2. 35 Further, we also provide basic characteristics of the system. 36 37While these viruses are present in the human population for a long time, they are believed to 43 enter the human population in a zoonotic event, and one may speculate that they may have 44 caused epidemics similar to the one observed for the SARS-CoV-2. Time to the most recent 45 ancestor analysis suggests that human coronavirus HCoV-NL63 is the oldest species in humans, 46 followed by its cousin HCoV-229E and two betacoronaviruses, which emerged in humans in a 47 relatively near past 1,2, 3,4 . In the 21 st century, we already faced the emergence of the three novel 48 coronaviruses in humans, of which SARS-CoV disappeared after one season never to come 49 back, and MERS-CoV never fully crossed the species border, as its transmission between 50 humans is highly ineffective 5,6,7 . The 2019 zoonotic transmission, however, resulted in the 51 emergence of a novel human coronavirus, which seems to carry an optimal set of features 52 allowing for its rapid spread with considerable mortality. Whether the virus will become 53 endemic in humans is an open question 8,9,10 . 54At present, the studies on the virus are carried out using a surrogate system based on the 55 immortalized simian Vero E6 cell line 11 . While this model is convenient for diagnostics and 56 testing of some antiviral drugs, it has serious limitations and does not allow for the 57 understanding of virus biology and evolution. To make an example, the entry route of human 58 coronaviruses varies between the cell lines and differentiated tissue, not mentioning the immune 59 responses or virus-host interactions 12,13,14 . 60Here we used the fully differentiated epithelium cultures to study the infection with the 61 novel human coronavirus SARS-CoV-2. We observed an efficient replication of the virus in 62 the tissue, with the maximal replication at 2 days post-infection. At the time of the study no 63 (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.antibodies were available. Therefore we developed immuno-FISH to show that the virus infects 64 primarily ciliated cells of the respiratory epithelium. 66Results and discussion 67 The HAE cultures reconstitute the tissue lining the conductive airways of humans. Fully 68 differentiated, are among the best tools for studying the viral infection in a natural 69 microenvironment 15 . These air-liquid interphase cultures contain a number of cell types (e.g., 70 basal, ciliated, and goblet). At the sa...

Objectives: Lung transplantation not only saves a patient's life but also creates the opportunity for becoming more self-reliant and getting back to work. The aim of this single center study was to assess the prospects of employment, as well as its influence on the quality of life and physical activity, of the lung transplant recipients of the Silesian Center for Heart Diseases in Zabrze, Poland. Material and Methods: A retrospective study covered 67 lung transplant recipients of the Silesian Center of Heart Diseases. Only patients with ≥ 6-month follow-up were included. All of the patients gave their written consent to be included in the study before filling out the questionnaire containing questions about employment, income, education and how work affected their quality of life before and after lung transplantation. A physical capability assessment was performed by climbing flights of stairs and by means of a 6-min walk test, and spirometry parameters were also measured. Results: Twenty of the patients included in the study (31.7%) were employed after lung transplantation, 63.2% of whom worked full-time. Profession was changed by 2 patients (14.3%). The patients diagnosed with cystic fibrosis were found to have the highest chance of finding employment after lung transplantation. The statistical analysis revealed that the employed patients were able to cover longer distances during the 6-min walk test (556 m, on average) than the unemployed ones (494 m, on average). Conclusions: One in 3 patients finds employment after lung transplantation. Work improves the quality of life of the majority of lung transplant recipients. The patients who are employed are also in a better physical condition, and they are more self-reliant in comparison to those who remain unemployed. Lung transplant recipients with cystic fibrosis are most likely to find employment, and so are patients with higher education. Int J Occup

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Despite significant advancements in pharmacological treatment, interventional and surgical options are still viable treatments for patients with pulmonary arterial hypertension (PAH), particularly idiopathic PAH. Herein, we review the interventional and surgical treatments for PAH. Atrial septostomy and the Potts shunt can be useful bridging tools for lung transplantation (Ltx), which remains the final surgical treatment among patients who are refractory to any other kind of therapy. Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) remains the ultimate bridging therapy for patients with severe PAH. More importantly, VA-ECMO plays a crucial role during Ltx and provides necessary left ventricular conditioning during the initial postoperative period. Pulmonary denervation may potentially be a new way to ensure better transplant-free survival among patients with the aforementioned disease. However, high-quality randomized controlled trials are needed. As established, obtaining the Eisenmenger physiology among patients with severe pulmonary hypertension by creating artificial defects is associated with improved survival. However, right-to-left shunting may be harmful after Ltx. Closure of the artificially created defects may carry some risk associated with cardiac surgery, especially among patients with Potts shunts. In conclusion, PAH requires an interdisciplinary approach using pharmacological, interventional, and surgical modalities.

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