Ongoing Exercise Intolerance Following COVID-19: A Magnetic Resonance-Augmented Cardiopulmonary Exercise Test Study.

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 (COVIDreduced) or fully recovered (COVIDnormal) exercise capacity; a group of age- and sex-matched healthy controls. The COVIDreducedgroup 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 COVIDnormal patients and controls. The COVIDreduced 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 COVIDnormal 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 m2) versus controls (6.0±1.2 L/min per m2; P=0.004) and COVIDnormal patients (5.7±1.5 L/min per m2; P=0.02), associated with lower indexed stroke volume (SVi:COVIDreduced 39±10 mL/min per m2 versus COVIDnormal 43±7 mL/min per m2 versus controls 48±10 mL/min per m2; 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.

The impact of the COVID-19 pandemic on home mechanical ventilation services: A national survey.

The COVID-19 pandemic has caused major disruption to healthcare services globally. We present the findings of a national survey of home mechanical ventilation (HMV) services in England and Wales. 30 HMV services (60%) responded. There was a significant reduction in outpatient services with 93% of services not offering routine face-to-face appointments, although most centres were able to offer emergency appointments for ventilation review and set-up. HMV inpatient capacity was reassigned, and HMV service staff re-deployed in the majority of centres (97%). The initial wave of the COVID-19 pandemic left a service backlog of a median of 87 outpatient appointments [range 0-1500] and a median of 4 patients (range 0-100) awaiting NIV set-up.

Local and systemic responses to SARS-CoV-2 infection in children and adults.

It is not fully understood why COVID-19 is typically milder in children1-3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.

Single-cell multi-omics analysis of the immune response in COVID-19.

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.