Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study

Background No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. Findings 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. Funding UK Research and Innovation and National Institute for Health Research

A cortical-inspired model for orientation-dependent contrast perception: a link with Wilson-Cowan equations

Comunicació presentada a: The 7th International Conference on Scale Space and Variational Methods in Computer Vision, celebrada del 30 de juny al 4 de juliol de 2019 a Hofgeismar, Alemanya.We consider a differential model describing neuro-physiological contrast percep- tion phenomena induced by surrounding orientations. The mathematical formulation relies on a cortical-inspired modelling [10] largely used over the last years to describe neuron inter- actions in the primary visual cortex (V1) and applied to several image processing problems [12,19,13]. Our model connects to Wilson-Cowan-type equations [23] and it is analogous to the one used in [3,2,14] to describe assimilation and contrast phenomena, the main novelty being its explicit dependence on local image orientation. To confirm the validity of the model, we report some numerical tests showing its ability to explain orientation-dependent phenom- ena (such as grating induction) and geometric-optical illusions [21,16] classically explained only by filtering-based techniques [6,18]

Cortical-inspired Wilson–Cowan-type equations for orientation-dependent contrast perception modelling

We consider the evolution model proposed in Bertalmío (Front Comput Neurosci 8:71, 2014), Bertalmío et al. (IEEE Trans Image Process 16(4):1058–1072, 2007) to describe illusory contrast perception phenomena induced by surrounding orientations. Firstly, we highlight its analogies and differences with the widely used Wilson–Cowan equations (Wilson and Cowan in BioPhys J 12(1):1–24, 1972), mainly in terms of efficient representation properties. Then, in order to explicitly encode local directional information, we exploit the model of the primary visual cortex (V1) proposed in Citti and Sarti (J Math Imaging Vis 24(3):307–326, 2006) and largely used over the last years for several image processing problems (Duits and Franken in Q Appl Math 68(2):255–292, 2010; Prandi and Gauthier in A semidiscrete version of the Petitot model as a plausible model for anthropomorphic image reconstruction and pattern recognition. SpringerBriefs in Mathematics, Springer, Cham, 2017; Franceschiello et al. in J Math Imaging Vis 60(1):94–108, 2018). The resulting model is thus defined in the space of positions and orientation, and it is capable of describing assimilation and contrast visual bias at the same time. We report several numerical tests showing the ability of the model to reproduce, in particular, orientation-dependent phenomena such as grating induction and a modified version of the Poggendorff illusion. For this latter example, we empirically show the existence of a set of threshold parameters differentiating from inpainting to perception-type reconstructions and describing long-range connectivity between different hypercolumns in V1.The authors acknowledge the anonymous referees for their suggestions which improved significantly the quality of their manuscript. M. B. acknowledges the support of the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 761544 (Project HDR4EU) and under Grant Agreement No. 780470 (Project SAUCE), and of the Spanish government and FEDER Fund, Grant Ref. PGC2018-099651-B-I00 (MCIU/AEI/FEDER, UE). L. C., V. F. and D. P. acknowledge the support of a public grant overseen by the French National Research Agency (ANR) as part of the Investissement d’avenir program, through the iCODE project funded by the IDEX Paris-Saclay, ANR-11-IDEX-0003-02 and of the research project LiftME funded by INS2I, CNRS. V. F. acknowledges the support received from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant No. 794592 and from the INdAM project Problemi isoperimetrici in spazi Euclidei e non. V. F. and D. P. also acknowledge the support of ANR-15-CE40-0018 project SRGI - Sub-Riemannian Geometry and Interactions. B. F. acknowledges the support of the Fondation Asile des Aveugles

The Neoarchaean Limpopo Orogeny: exhumation and regional-scale gravitational crustal overturn driven by a granulite diapir

Integrated geological, geochronological and geophysical data from the Neoarchaean Limpopo Complex (LC) and adjacent granite-greenstone terrane of the Northern Kaapvaal Craton (NKVC) demonstrates the following three key features. (1) The LC-NKVC tectonic boundary defined by the Hout River Shear Zone (HRSZ) played a fundamental role in establishing high-grade metamorphic domains in the Southern Marginal Zone (SMZ) of the LC. These domains are characterized by their specific retrograde P-T evolution, (2) Near-isobaric southward thrusting of a hot allochthonous SMZ nappe with imbedded steeply plunging folds and steep shear zones against and over the NKVC along the HRSZ before ca. 2.68 Ga occurred as a consequence of steep exhumation within the Central Zone (CZ) at 2.72–2.62 Ga. (3) Initial exhumation of the CZ to mid-crustal levels before ca. 2.68 Ga was associated with isoclinal folding and melt-weakened domes and directed the southwards channelling of the hot nappe. Final exhumation of the CZ to the upper crust at 2.65–2.62 Ga was driven by granitic diapirism and the 32 formation of shear-related, mega-scale closed structures. These features favour an intracrustal Neoarchaean Limpopo orogeny as the result of a granulite diapir triggered by mantle heat-fluid flow underneath the CZ at 2.72–2.62 Ga. The data is neither compatible with continent collisional models nor with an Archean accretionary orogen along the northern edge of the Kaapvaal Craton that is linked to the collision of the Pietersburg Block with the C