Controversies in the Science of Sedentary Behaviour and Health: Insights, Perspectives and Future Directions from the 2018 Queensland Sedentary Behaviour Think Tank

The development in research concerning sedentary behaviour has been rapid over the past two decades. This has led to the development of evidence and views that have become more advanced, diverse and, possibly, contentious. These include the effects of standing, the breaking up of prolonged sitting and the role of moderate-to-vigorous physical activity (MVPA) in the association between sedentary behaviour and health outcomes. The present aim is to report the views of experts (n = 21) brought together (one-day face-to-face meeting in 2018) to consider these issues and provide conclusions and recommendations for future work. Each topic was reviewed and presented by one expert followed by full group discussion, which was recorded, transcribed and analysed. The experts concluded that (a). standing may bring benefits that accrue from postural shifts. Prolonged (mainly static) standing and prolonged sitting are both bad for health; (b). ‘the best posture is the next posture’. Regularly breaking up of sitting with postural shifts and movement is vital; (c). health effects of prolonged sitting are evident even after controlling for MVPA, but high levels of MVPA can attenuate the deleterious effects of prolonged sitting depending on the health outcome of interest. Expert discussion addressed measurement, messaging and future directions

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice