Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID.

BACKGROUND: COVID-19 is associated with a dysregulated immune response but it is unclear how immune dysfunction contributes to the chronic morbidity persisting in many COVID-19 patients during convalescence (long COVID). METHODS: We assessed phenotypical and functional changes of monocytes in COVID-19 patients during hospitalisation and up to 9 months of convalescence following COVID-19, respiratory syncytial virus or influenza A. Patients with progressive fibrosing interstitial lung disease were included as a positive control for severe, ongoing lung injury. RESULTS: Monocyte alterations in acute COVID-19 patients included aberrant expression of leukocyte migration molecules, continuing into convalescence (n=142) and corresponding with specific symptoms of long COVID. Long COVID patients with unresolved lung injury, indicated by sustained shortness of breath and abnormal chest radiology, were defined by high monocyte expression of C-X-C motif chemokine receptor 6 (CXCR6) (p<0.0001) and adhesion molecule P-selectin glycoprotein ligand 1 (p<0.01), alongside preferential migration of monocytes towards the CXCR6 ligand C-X-C motif chemokine ligand 16 (CXCL16) (p<0.05), which is abundantly expressed in the lung. Monocyte CXCR6 and lung CXCL16 were heightened in patients with progressive fibrosing interstitial lung disease (p<0.001), confirming a role for the CXCR6-CXCL16 axis in ongoing lung injury. Conversely, monocytes from long COVID patients with ongoing fatigue exhibited a sustained reduction of the prostaglandin-generating enzyme cyclooxygenase 2 (p<0.01) and CXCR2 expression (p<0.05). These monocyte changes were not present in respiratory syncytial virus or influenza A convalescence. CONCLUSIONS: Our data define unique monocyte signatures that define subgroups of long COVID patients, indicating a key role for monocyte migration in COVID-19 pathophysiology. Targeting these pathways may provide novel therapeutic opportunities in COVID-19 patients with persistent morbidity.

Active and latent TB screening in recently arrived persons from Afghanistan: feasibility and lessons learned.

We describe an active and latent tuberculosis (TB) screening programme undertaken in Manchester, UK in response to the arrival of a cohort of refugees from Afghanistan. In total, 217 adults and 347 children were offered screening, which involved a symptom questionnaire, Mantoux test or interferon gamma release assay, blood-borne virus screening and a chest X-ray in participants over the age of 11. We found a latent TB infection (LTBI) rate of 15% in adults and 1.5% in children, which is lower than global LTBI estimates. One case of active TB was detected. Screening was undertaken in the hotels where participants were temporarily housed, leading to high participant engagement levels. Attendance rates were almost doubled compared with a previous hospital-based screening programme. Hotel-based screening for TB presented several challenges, including transfer of information and results to secondary care. Understanding these challenges and learning from the programme has helped us refine our screening protocol to optimise migrant TB screening in Manchester in the future.

Active and latent TB screening in recently arrived persons from Afghanistan: feasibility and lessons learned.

We describe an active and latent tuberculosis (TB) screening programme undertaken in Manchester, UK in response to the arrival of a cohort of refugees from Afghanistan. In total, 217 adults and 347 children were offered screening, which involved a symptom questionnaire, Mantoux test or interferon gamma release assay, blood-borne virus screening and a chest X-ray in participants over the age of 11. We found a latent TB infection (LTBI) rate of 15% in adults and 1.5% in children, which is lower than global LTBI estimates. One case of active TB was detected. Screening was undertaken in the hotels where participants were temporarily housed, leading to high participant engagement levels. Attendance rates were almost doubled compared with a previous hospital-based screening programme. Hotel-based screening for TB presented several challenges, including transfer of information and results to secondary care. Understanding these challenges and learning from the programme has helped us refine our screening protocol to optimise migrant TB screening in Manchester in the future.

Alterations in T and B cell function persist in convalescent COVID-19 patients.

BACKGROUND: Emerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these patients presently remains ill-defined. METHODS: Here, we describe the phenotypic and functional characteristics of B and T cells in hospitalized COVID-19 patients during acute disease and at 3-6 months of convalescence. FINDINGS: We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic program evident in CD8+ T cells as well as elevated production of type 1 cytokines and interleukin-17 (IL-17). Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/IL-10 cytokine imbalance in response to Toll-like receptor activation, skewed toward a pro-inflammatory phenotype. Whereas the frequency of IL-6+ B cells was restored in convalescent patients irrespective of clinical outcome, the recovery of IL-10+ B cells was associated with the resolution of lung pathology. CONCLUSIONS: Our data detail lymphocyte alterations in previously hospitalized COVID-19 patients up to 6 months following hospital discharge and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes, with 1 subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalization with COVID-19 could affect longer-term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients. FUNDING: Provided by UKRI, Lister Institute of Preventative Medicine, the Wellcome Trust, The Kennedy Trust for Rheumatology Research, and 3M Global Giving.

A Medical Article Publishing Club for Junior Doctors: A Quantitative and Qualitative Analysis.

Introduction There is an increasing expectation for junior doctors to have a publication. However, there is not much help provided to bridge the gap between project completion or case reporting and getting published. Our previous study demonstrated that junior doctors felt that involvement in medical article publishing contributes to learning and that it is an effective teaching method. Junior doctors also agreed that it is difficult to get published. Based on this study we started a medical article publishing (MAP) club. The aim of this study was to assess user satisfaction with the MAP club. Materials and methods Questionnaires were sent to 12 doctors who obtained advice from the MAP club since its inception in December 2017. The questionnaire contained two questions: (1) how useful they found the advice and guidance received and (2) how likely they were to recommend the MAP club to their colleagues. The 10-point Likert scale responses were analyzed quantitatively. Written comments and suggestions were analyzed qualitatively by thematic analysis. Results Respondents gave scores of either 9 or 10 to both questions indicating that they found the advice and guidance received very useful and that they were very likely to recommend the MAP club to their colleagues (weighted scores 9.75 and 9.92, respectively). The thematic analysis revealed three main themes: (1) positive features of the MAP club, (2) what participants gained from the MAP club and (3) recommendations for the future. The majority of respondents commented that the club was useful, helpful, supportive, and informative. More than a third commented that the club provided encouragement, confidence, practical tips, learning experience, and the opportunity to publish. A similar proportion asked that we keep the club going and provide dedicated teaching sessions. Conclusions Junior doctors feel that the MAP club has positive features and has contributed to their learning, education, and publishing skills. A proportion of them would also like to receive formal teaching sessions concerning medical article publishing. This study has highlighted the benefits and importance of establishing a medical article publishing club for junior doctors.