Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19.

Although alterations in myeloid cells have been observed in COVID-19, the specific underlying mechanisms are not completely understood. Here, we examine the function of classical CD14+ monocytes in patients with mild and moderate COVID-19 during the acute phase of infection and in healthy individuals. Monocytes from COVID-19 patients display altered expression of cell surface receptors and a dysfunctional metabolic profile that distinguish them from healthy monocytes. Secondary pathogen sensing ex vivo leads to defects in pro-inflammatory cytokine and type-I IFN production in moderate COVID-19 cases, together with defects in glycolysis. COVID-19 monocytes switch their gene expression profile from canonical innate immune to pro-thrombotic signatures and are functionally pro-thrombotic, both at baseline and following ex vivo stimulation with SARS-CoV-2. Transcriptionally, COVID-19 monocytes are characterized by enrichment of pathways involved in hemostasis, immunothrombosis, platelet aggregation and other accessory pathways to platelet activation and clot formation. These results identify a potential mechanism by which monocyte dysfunction may contribute to COVID-19 pathology.

The high-quality health system 'revolution': Re-imagining tuberculosis infection prevention and control.

The Lancet Commission on High-Quality Health Systems called for a 'revolution' in the quality of care provided in low- and middle-income countries. We argue that this provides a helpful framework to demonstrate how effective tuberculosis infection prevention and control (TB IPC) implementation should be linked with health system strengthening, moving it from the silo of the national TB programmes. Using this framework, we identify and discuss links between TB IPC implementation and patient safety, human resources for health, prioritising person-centred care, building trust in health systems and refining the tools used to measure TB IPC implementation. Prioritising patient experience has been a recent addition to the definition of high-quality care. In high TB burden settings, the encounter with TB IPC measures may be a TB patient's initial contact with the healthcare system and may cause feelings of stigmatisation. We advocate for re-imagining the way we implement TB IPC, by drawing on the principles of person-centred care through incorporating the experiences of people using healthcare services. Health workers who developed occupational TB also offer a unique perspective: they have both experienced TB IPC and have played a role in implementing it in their workplace. They can be powerful advocates for person-centred TB IPC implementation. Through framing TB IPC as part of health system strengthening and consciously including person-centred perspectives in TB IPC design, measurement and guidelines, we hope to influence future TB IPC research and practice.