Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed ~140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with ~30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-γ production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease.

No abstract

No abstract

Being the vital element of successful cities, public spaces play an important role in achieving sustainable development goals and in coping with climate change. The new urban agenda considers public spaces indispensable for sustaining the productivity of cities, social cohesion and inclusion, civic identity, and quality of life. Accordingly, there is no doubt about the importance of public spaces, while their quality is generated through the symbiosis of various elements. On the basis of normative theories of urban design, several public space design frameworks have been established in order to define what makes a good public place. Such a framework for public space quality evaluation is developed and tested at the Chair for Planning and Design in Landscape Architecture at the University of Belgrade—Faculty of Forestry. The framework covers six criteria which illuminate key aspects of public spaces: safety and security, accessibility, legibility, comfort, inspiration and sensitivity and liveability. In this research, special attention is paid to the criteria of comfort analysed on two scale levels in Belgrade, Serbia. In the past, Belgrade was affected by extreme weather events that caused serious and sometimes disastrous consequences. The most pronounced challenges among them are heat waves in summer that, due to the shortage of vegetation combined with the proliferation of tarmac and concrete surfaces and reduced air ventilation, particularly threaten the densely populated central municipalities of Stari Grad, Savski Venac and Vracar. The first scale level covers the analysis of the public space network and the degree of establishment of green infrastructure in Lower Dorcol quartier, which is located in the Municipality of Stari Grad, using quantitative and qualitative indicators and GIS (Geographic Information System) digital tools. The aim of this study is to observe the actual state of the public space network and to define a future scenario of its development in line with climate change challenges. Jevrejska Street, as an element of the above-mentioned public space network, is the subject of the next phase of the research. The study on this scale level will cover qualitative and quantitative analysis of public space elements such as paving, urban equipment, greenery, lighting, water facilities, etc. Next to that, by using the ENVI Met platform, the actual and proposed improvement of the street will be explored. The final part of this research will include a discussion about the research methodology used in order to improve the public space design process and to point out the need for the careful consideration of comfort as an important aspect of good public space.