Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK:a prospective multicentre cohort study

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect. INTERPRETATION: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. FUNDING: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Расчетное обоснование механической безопасности стадионов к Чемпионату мира по футболу 2018 года

It is obvious that contemporary design and construction of unique buildings and structures is unthinkable without mathematical (numerical) and computer modelling and advanced analysis ofload-bearing structures under various kinds ofloads and impacts. One of the most ambitious and important construction projects is the uniquelarge-span structures. These are, in particular, stadiums, sports palaces and water parks, shopping malls, pedestrian, road and railway bridges of various design solutions. The distinctive paper is devoted to theoretical foundations and results of mathematical (numerical) modeling of the state (in terms of the analysis of stress-strain state, strength and stability) of football stadiums built for the 2018 FIFA World Cup in Russia. Finite element method is used for approximation and high-precision numerical solution of corresponding boundary problems of structural mechanics. It is the most universal and powerful numerical method of mechanics. The paper, in particular, describes some features of development of finite element models and the main results of the analysis of the mechanical (structural) safety of three-dimensional large-span systems "soil foundation - reinforced concrete structures of foundations and stands - steel structures of the coating and facades" of these football stadiums with the basic and specialload combinations. In addition, the key procedures of scientific support during the corresponding expertise and assessments are outlined. Generally, socially significant and knowledge-intensive problem of providing mechanical (constructive) safety of unique combined objects of construction (three-dimensional systems "foundation -reinforced concrete structures of foundations and stands - steel structures of coating and facades") has been solved at a new level as a result of the performed complex of research works.Очевидно, что современное проектирование и строительство уникальных зданий, сооружений и комплексов требует расчётного обоснования и глубоких всесторонних исследований поведения несущих конструкций под действием разного рода факторов. Одними из наиболее грандиозных и ответственных объектов строительства являются уникальные большепролётные сооружения. Это, в частности, стадионы, дворцы спорта и аквапарки, торгово-развлекательные комплексы, пешеходные, автомобильные и железнодорожные мосты различных конструктивных решений. В настоящей статье представлены теоретические основы и результаты математического (численного) моделирования состояния [в части анализа напряжённо-деформированного состояния (НДС), прочности и устойчивости] российских футбольных стадионов, возведённых к чемпионату мира по футболу 2018 года. Для дискретизации по пространству и решения соответствующих краевых задач строительной механики был применён самый универсальный и мощный современный численный метод механики - метод конечных элементов (МКЭ). В статье, в частности, описаны некоторые особенности создания соответствующих расчётных моделей и основные результаты расчётного обоснования механической безопасности трёхмерных большепролётных систем «грунтовое основание - железобетонные конструкции фундаментов и трибун - металлические конструкции покрытия и фасадов» указанных футбольных стадионов при основных и особых сочетаниях нагрузок. Кроме того, кратко изложены ключевые процедуры научного сопровождения при прохождении экспертизы. В целом, в результате выполненного комплекса научно-исследовательских работ на новом уровне решена социально значимая и наукоёмкая проблема обеспечения механической (конструктивной) безопасности уникальных комбинированных объектов строительства (трёхмерных систем «основание - железобетонные конструкции фундаментов и трибун - металлоконструкции покрытия и фасадов»)

Features of the structural safety analysis (strain-stress state, dynamics, strength and stability) of stadiums for the 2018 FIFA World Cup in Russia

The article presents special features of numerical simulation and main results of structural safety analysis of the three-dimensional long-span systems "ground base - reinforced concrete foundation structures and stands - metal structures of the coating and facades" of football stadiums for the 2018 World Cup in Russia with basic and special combinations of loads and key procedures of scientific support during examination. A brief description is given of the component mode synthesis as applied to the calculation of structures of this type. © Published under licence by IOP Publishing Ltd

Numerical simulation of loads and impacts, stress-strain state, strength and stability of unique structures, buildings and facilities. Experience of StaDyO research & engineering centre

The paper contains analytical overview of the most important unique/critical objects and the computational analysis problems of the mechanical safety, carried out by the team of Research & Development Centre StaDyO (StaDyO R&D Centre) researchers for the last two years (2016-2018). Corresponding complex coupled problems of continuum mechanics were solved with the use of contemporary methods and models of numerical modeling (nonlinear models, coupled problems, substructures, submodeling, etc.), implemented in verified software complexes. Some of these results are briefly considered and analyzed. Conclusions about the main directions of further research and development are presented as well. © Published under licence by IOP Publishing Ltd