Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

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Objectives:An exploratory investigation is reported into the role of spirituality and religious practice in protecting against depression among older people living in rural villages in Bulgaria and Romania, two neighbouring countries with similar cultural, political and religious histories, but with differing levels of current religiosity. Methods:In both countries interviews were conducted with samples of 160 persons of 60 years and over in villages of similar socio-economic status. The HAD-D scale and the Royal Free Interview for Religious and Spiritual Beliefs were used to assess depression and spiritual belief and practice respectively. In addition social support, physical functioning and the presence of chronic diseases were assessed. One year later follow-up interviews were conducted with 58 of the original sample in Bulgaria, in which additional measures of depression and of spiritual belief and practice were also included. Results:The study demonstrates, as expected, significantly lower levels of spiritual belief in the Bulgarian sample, as well as significantly higher levels of depression, the latter attributable in large part to higher morbidity and disability rates, but less evidently to differences in strength of belief. However analyses from both the cross-sectional study and the one year follow-up of the Bulgarian sample do suggest that spiritual belief and practice both influence and reflect physical and mental illness. Conclusions:Religious and spiritual belief and practice constitute important means of coping with both physical and mental health problems in later life. Further investigation of their protective role is encouraged in populations of diverse religiosity.

The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well as economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling of over 800,000 peripheral blood mononuclear cells from a cohort of 130 patients with COVID-19. Our cohort, from three UK centres, spans the spectrum of clinical presentations and disease severities ranging from asymptomatic to critical. Three control groups were included: healthy volunteers, patients suffering from a non-COVID-19 severe respiratory illness and healthy individuals administered with intravenous lipopolysaccharide to model an acute inflammatory response. Full single cell transcriptomes coupled with quantification of 188 cell surface proteins, and T and B lymphocyte antigen receptor repertoires have provided several insights into COVID-19: 1. a new non-classical monocyte state that sequesters platelets and replenishes the alveolar macrophage pool; 2. platelet activation accompanied by early priming towards megakaryopoiesis in immature haematopoietic stem/progenitor cells and expansion of megakaryocyte-primed progenitors; 3. increased clonally expanded CD8+ effector:effector memory T cells, and proliferating CD4+ and CD8+ T cells in patients with more severe disease; and 4. relative increase of IgA plasmablasts in asymptomatic stages that switches to expansion of IgG plasmablasts and plasma cells, accompanied with higher incidence of BCR sharing, as disease severity increases. All data and analysis results are available for interrogation and data mining through an intuitive web portal. Together, these data detail the cellular processes present in peripheral blood during an acute immune response to COVID-19, and serve as a template for multi-omic single cell data integration across multiple centers to rapidly build powerful resources to help combat diseases such as COVID-19.

Background Ongoing exercise intolerance of unclear cause following COVID‐19 infection is well recognized but poorly understood. We investigated exercise capacity in patients previously hospitalized with COVID‐19 with and without self‐reported exercise intolerance using magnetic resonance–augmented cardiopulmonary exercise testing. Methods and Results Sixty subjects were enrolled in this single‐center prospective observational case‐control study, split into 3 equally sized groups: 2 groups of age‐, sex‐, and comorbidity‐matched previously hospitalized patients following COVID‐19 without clearly identifiable postviral complications and with either self‐reported reduced (COVID reduced ) or fully recovered (COVID normal ) exercise capacity; a group of age‐ and sex‐matched healthy controls. The COVID reduced group had the lowest peak workload (79W [Interquartile range (IQR), 65–100] versus controls 104W [IQR, 86–148]; P =0.01) and shortest exercise duration (13.3±2.8 minutes versus controls 16.6±3.5 minutes; P =0.008), with no differences in these parameters between COVID normal patients and controls. The COVID reduced group had: (1) the lowest peak indexed oxygen uptake (14.9 mL/minper kg [IQR, 13.1–16.2]) versus controls (22.3 mL/min per kg [IQR, 16.9–27.6]; P =0.003) and COVID normal patients (19.1 mL/min per kg [IQR, 15.4–23.7]; P =0.04); (2) the lowest peak indexed cardiac output (4.7±1.2 L/min per m 2 ) versus controls (6.0±1.2 L/min per m 2 ; P =0.004) and COVID normal patients (5.7±1.5 L/min per m 2 ; P =0.02), associated with lower indexed stroke volume (SVi:COVID reduced 39±10 mL/min per m 2 versus COVID normal 43±7 mL/min per m 2 versus controls 48±10 mL/min per m 2 ; P =0.02). There were no differences in peak tissue oxygen extraction or biventricular ejection fractions between groups. There were no associations between COVID‐19 illness severity and peak magnetic resonance–augmented cardiopulmonary exercise testing metrics. Peak indexed oxygen uptake, indexed cardiac output, and indexed stroke volume all correlated with duration from discharge to magnetic resonance–augmented cardiopulmonary exercise testing ( P <0.05). Conclusions Magnetic resonance–augmented cardiopulmonary exercise testing suggests failure to augment stroke volume as a potential mechanism of exercise intolerance in previously hospitalized patients with COVID‐19. This is unrelated to disease severity and, reassuringly, improves with time from acute illness.

While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection between children and adults may provide important clues about the pathogenesis of SARS-CoV-2 infection. To address this, we first generated a healthy reference multi-omics single cell data set from children (n=30) in whom we have profiled triple matched samples: nasal and tracheal brushings and PBMCs, where we track the developmental changes for 42 airway and 31 blood cell populations from infancy, through childhood to adolescence. This has revealed the presence of naive B and T lymphocytes in neonates and infants with a unique gene expression signature bearing hallmarks of innate immunity. We then contrast the healthy reference with equivalent data from severe paediatric and adult COVID-19 patients (total n=27), from the same three types of samples: upper and lower airways and blood. We found striking differences: children with COVID-19 as opposed to adults had a higher proportion of innate lymphoid and non-clonally expanded naive T cells in peripheral blood, and a limited interferon-response signature. In the airway epithelium, we found the highest viral load in goblet and ciliated cells and describe a novel inflammatory epithelial cell population. These cells represent a transitional regenerative state between secretory and ciliated cells; they were found in healthy children and were enriched in pediatric and adult COVID-19 patients. Epithelial cells display an antiviral and neutrophil-recruiting gene signature that is weaker in severe paediatric versus adult COVID-19. Our matched blood and airway samples allowed us to study the spatial dynamics of infection. Lastly, we provide a user-friendly interface for this data as a highly granular reference for the study of immune responses in airways and blood in children.

BackgroundMalignant pleural effusion (MPE) results in breathlessness and impairment of health-related quality of life (HRQOL). This study reviews the existing literature on HRQOL following invasive interventions in MPE.MethodsFive electronic databases were systematically searched and assessed three times during the review process and last completed on 15 June 2018. We included all studies evaluating HRQOL outcomes for the following interventions: therapeutic thoracocentesis, talc slurry (TS) pleurodesis, indwelling pleural catheter (IPC) insertion and thoracoscopic talc poudrage (TTP) pleurodesis. Meta-analysis was not performed due to substantial heterogeneity in the published data.Results17 studies were included in the review reporting HRQOL outcomes in 2515 patients. TTP, TS and IPC were associated with modest but inconsistent improvements in HRQOL up to 12 weeks. No intervention was significantly different from another in HRQOL outcomes at any time point. The attrition to follow-up was 48.3% (664/1374) at 3 months. The overall quality of studies was inadequate.ConclusionTTP, TS and IPC seem to improve HRQOL in MPE over 4–12 weeks, but there are insufficient longer term data due to high attrition rates. Evidence on the most effective treatment strategy is limited by the small number of randomised or comparative studies.Trial registration numberCRD42016051003.