Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. MethodsThe Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A posthoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5•9 months (IQR 4•9-6•5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity.Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments w...

The National COVID-19 Chest Imaging Database (NCCID) is a repository of chest radiographs, CT and MRI images and clinical data from COVID-19 patients across the UK, to support research and development of AI technology and give insight into COVID-19 disease https://bit.ly/3eQeuha

Cholinergic neurons of the striatum play a crucial role in controlling output from this region. Their firing is under the control of a relatively limited glutamatergic input, deriving principally from the thalamus. Glutamate transmission is effected via three major subtypes of receptors, including those with affinity for N-methyl-D-aspartate (NMDA) and the properties of individual receptors reflect their precise subunit composition. We examined the distribution of NMDA2C and NMDA2D subunits in the rat striatum using immunocytochemistry and show that a population of large neurons is strongly immunoreactive for NMDA2D subunits. From their morphology and ultrastructure, these neurons were presumed to be cholinergic and this was confirmed with double immunofluorescence. We also show that NMDA2C is present in a small number of septal and olfactory cortical neurons but absent from the striatum.Receptors that include NMDA2D subunits are relatively insensitive to magnesium ion block making neurons more likely to fire at more negative membrane potentials. Their localization to cholinergic neurons may enable very precise regulation of firing of these neurons by relatively small glutamatergic inputs. Keywordsinterneuron; ultrastructure; synapse; endoplasmic reticulumThe cholinergic neurons of the striatum play an important role in basal ganglia control of voluntary movement. They represent only 1-2% of striatal neurons but their extensive local axon collateral system, innervating both medium-sized densely spiny neurons (MSN) (Izzo and Bolam, 1988) and other local circuit neurons (Koos and Tepper, 2002) is consistent with a primary role in determining the final activity of striatal output neurons (Calabresi et al., 2000). While the majority of glutamatergic input to MSN originates in the cortical regions, excitatory input to these tonically active, cholinergic striatal neurons comes almost exclusively from the parafascicular thalamic nucleus (Lapper and Bolam, 1992;Zhou et al., 2002) and possibly from the cortex (Thomas et al., 2000), and principally from the midline/intralaminar thalamic nuclei to the ventral striatum (Meredith and Wouterlood, 1990 The firing of cholinergic neurons is under the control of a relatively few inputs and interactions are subserved by a number of different glutamate receptor subtypes. Although no AMPA subunits have been reported (Chen et al., 1996;Fujiyama et al., 2004), cholinergic neurons express kainate GluR5, 6 and 7 subunits (Chen et al., 1996). Moreover, stimulation of metabotropic receptor subunits, mGluR1-3, 5 and 7 (Bell et al., 2002) exerts a profound effect on cell excitability (Di Chiara et al., 1994). In addition, N-methyl-D-aspartate (NMDA) agonists potentiate striatal acetylcholine release (Giovannini et al., 1995) while direct stimulation of the thalamostriatal pathway increases acetylcholine release, via action on N-methyl-D-aspartate receptors (NR) (Consolo et al., 1996). Double labeling studies combining in situ hybridization for subunit mRNA with immunolabeling with a...