ALTERED GUT MICROBIOTA and RESPIRATORY DYSFUNCTION 3 MONTHS after SEVERE COVID-19

Background: Although COVID-19 is primarily a respiratory infection, mounting evidence suggests that the GI tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and associate with long-term respiratory dysfunction is unknown. Methods: From the NOR-Solidarity trial (n=181), plasma was collected during hospital admission and after three months, and analyzed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring diffusing capacity of the lungs for carbon monoxide (DLCO), and rectal swabs for gut microbiota analyses were collected (n= 97) and analysed by sequencing of the 16S rRNA gene. Results: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below lower limit of normal three months after hospitalization. These patients also had an altered global gut microbiota composition (Fig. 1), with reduced abundance of Erysipelotrichaceae UCG-003 and increased abundance of Flavonifractor and Veillonella, the latter potentially being linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2/fiO2-(P/F-ratio)<26.6 kPa. LBP levels remained elevated during and after hospitalization, and were associated with low-grade inflammation and respiratory dysfunction after three months. Figure 1 legend: Gut microbial composition in patients with respiratory dysfunction at the three-month follow-up (DLCO<="" div=""> Conclusion: Respiratory dysfunction after COVID-19 is associated with reduced biodiversity and gut microbiota alterations, along with persistently elevated LBP levels. Our results point to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID.

Management practices impacting on the rostering of medical scientists in the Australian healthcare sector

Purpose This study examines the management rostering systems that inform the ways medical scientists are allocated their work in the public healthcare sector in Australia. Promoting the contributions of medical scientists should be a priority given the important roles they are performing in relation to COVID-19 and the demand for medical testing doubling their workloads (COVID-19 National Incident Room Surveillance Team, 2020). This study examines the impact of work on medical scientists and rostering in a context of uncertain work conditions, budget restraints and technological change that ultimately affect the quality of patient care. This study utilises the Job-Demands-Resources theoretical framework (JD-R) to examine the various job demands on medical scientists and the resources available to them. Design/methodology/approach Using a qualitative methodological approach, this study conducted 23 semi-structured interviews with managers and trade union officials and 9 focus groups with 53 medical scientists, making a total 76 participants from four large public hospitals. Findings Due to increasing demands for pathology services, this study demonstrates that a lack of job resources, staff shortages, poor rostering practices such as increased workloads that lead to absenteeism, often illegible handwritten changes to rosters and ineffectual management lead to detrimental consequences for medical scientists' job stress and well-being. Moreover, medical science work is hidden and not fully understood and often not respected by other clinicians, hospital management or the public. These factors have contributed to medical scientists' lack of control over their work and causes job stress and burnout. Despite this, medical scientists use their personal resources to buffer the effects of excessive workloads and deliver high quality of patient care. Originality/value Findings suggest that developing mechanisms to promote sustainable employment practices for medical scientists are critical for the escalating demands in pathology.

Critical COVID-19 is associated with distinct leukocyte phenotypes and transcriptome patterns.

BACKGROUND: Prognostic markers for disease severity and identification of therapeutic targets in COVID-19 are urgently needed. We have studied innate and adaptive immunity on protein and transcriptomic level in COVID-19 patients with different disease severity at admission and longitudinally during hospitalization. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected at three time points from 31 patients included in the Norwegian SARS-CoV-2 cohort study and analysed by flow cytometry and RNA sequencing. Patients were grouped as either mild/moderate (n = 14), severe (n = 11) or critical (n = 6) disease in accordance with WHO guidelines and compared with patients with SARS-CoV-2-negative bacterial sepsis (n = 5) and healthy controls (n = 10). RESULTS: COVID-19 severity was characterized by decreased interleukin 7 receptor alpha chain (CD127) expression in naïve CD4 and CD8 T cells. Activation (CD25 and HLA-DR) and exhaustion (PD-1) markers on T cells were increased compared with controls, but comparable between COVID-19 severity groups. Non-classical monocytes and monocytic HLA-DR expression decreased whereas monocytic PD-L1 and CD142 expression increased with COVID-19 severity. RNA sequencing exhibited increased plasma B-cell activity in critical COVID-19 and yet predominantly reduced transcripts related to immune response pathways compared with milder disease. CONCLUSION: Critical COVID-19 seems to be characterized by an immune profile of activated and exhausted T cells and monocytes. This immune phenotype may influence the capacity to mount an efficient T-cell immune response. Plasma B-cell activity and calprotectin were higher in critical COVID-19 while most transcripts related to immune functions were reduced, in particular affecting B cells. The potential of these cells as therapeutic targets in COVID-19 should be further explored.

Provision of a consistent national approach to radiation therapy workforce protection measures in Australia during the COVID-19 pandemic

Healthcare workers are at the frontline managing COVID-19 patients with transmission of the COVID-19 virus to healthcare workers evident in many Australian states. Minimisation of this spread is vital to protecting the healthcare workforce with individual organisations detailing best practice for infection and control. However, interpretation and implementation of infection control guidelines is varied across Australian Radiation Therapy Departments, highlighting inconsistencies. Strong leadership, quality communication and clear direction is required during this crisis to ensure that radiation therapists receive all necessary support and resources required to maintain safety and well-being during the COVID-19 pandemic.