Cognitive and psychiatric symptom trajectories 2–3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK

Background COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2–3 years, and whether symptoms at 2–3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2–3 years were associated with occupation change. People with lived experience were involved in the study. Findings 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2–3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16–1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2–3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2–3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0–48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0–17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2–3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6–31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04–2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21–1·98] for every point increase in CCI-20). Interpretation Psychiatric and cognitive symptoms appear to increase over the first 2–3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19. Funding National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. Funding: UK Research and Innovation and National Institute for Health Research

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

Effects of Surface Micro-Geometry On the Lift-Off Speed of an EHL Contact

With decreasing speed the film thickness in an EHL contact decreases. Below a certain speed asperity contact will take place and gradually the contact enters the mixed lubrication regime. Vice-versa, with increasing speed beyond a certain speed the film thickness has reached a level where asperity contacts have become so rare that the contact will be in the full film regime.\ud \ud It seems only logical to expect that the speed at which the first (or last) significant asperity interactions start to take place is influenced by the micro-geometry of the surfaces. In experiments performed on a two-disk rig under conditions of pure rolling, using one very smooth and one rough disk it was indeed observed that the “lift-off” speed defined as the speed above which full film lubrication prevails, differed significantly for surfaces with a different micro-geometry. The test results can be seen as ranking for the surface micro-geometries in terms of their film generating capability. In this paper the question is addressed if a ranking as observed in the tests can be predicted in advance, using the load conditions and the measured surface micro-geometry as input, without having to resort to full-scale numerical simulations of any sort.\ud \ud Based on the amplitude reduction formula proposed by Venner et al. (2000), for roughness in contacts under pure rolling a model is constructed that, given the load condition and a measured surface micro-geometry, determines the deformed micro-geometry and subsequently a measure of “probability of contact.” For a given contact this measure can be plotted as a function of speed to obtain a theoretical “lift-off” curve. For the different types of surface micro-geometries used in the tests such a curve is compared with the experimental results, showing a promising agreement in ranking. \u

Influence of surface topography on friction, film breakdown and running-in in the mixed lubrication regime

The influence of surface topography on the lubricant film build-up ability and the friction characteristics of potential rolling bearing surfaces has been investigated by experiments on two-disc rigs. Traction-friction torque measurements were made for a variety of surface combinations, together with measurement of the electrical resistance between the discs as an indication of surface separation. For all disc combinations, running-in of the surfaces under load at any slide-roll ratio led eventually to full film separation. Contrary to results reported in the literature, film breakdown did not always increase with slip but depended on certain aspects of the surface structure. Friction torque measurements in the mixed lubrication regime also confirmed that friction is not determined simply by an Ra value. By suitable modification of the surface topography, keeping Ra constant, friction can be varied by as much as 10 per cent

Vitamin K deficiency bleeding after NICE guidance and withdrawal of Konakion Neonatal: British Paediatric Surveillance Unit study, 2006-2008.

To survey vitamin K deficiency bleeding (VKDB) and document vitamin K (VK) prophylaxis practice, and compare with findings predating withdrawal of Konakion Neonatal and guidance from the National Institute of Health and Clinical Excellence (NICE), both occurring in 2006.This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text from the publisher's site

Laboratory Evaluation of Underwater Grouting of CPP-603 Basins

A project is underway to deactivate a Fuel Storage Basin. The project specifies the requirements and identifies the tasks that will be performed for deactivation of the CPP- 603 building at the Idaho Nuclear Technology and Engineering Center of the Idaho National Engineering and Environmental Laboratory. The Fuel Receiving and Storage Building (CPP- 603) was originally used to receive and store spent nuclear fuel from various facilities. The area to undergo deactivation includes the three spent nuclear fuel storage basins and a transfer canal (1.5 million gallons of water storage). Deactivation operations at the task site include management of the hot storage boxes and generic fuel objects, removal of the fuel storage racks, basin sludge, water evaporation and basin grouting, and interior equipment, tanks, and associated components. This includes a study to develop a grout formulation and placement process for this deactivation project. Water will be allowed to passively evaporate to r educe the spread of contamination from the walls of the basin. The basins will be filled with grout, underwater, as the water evaporates to maintain the basin water at a safe level. The objective of the deactivation project is to eliminate potential exposure to hazardous and radioactive materials and eliminate potential safety hazards associated with the CPP-603 building

Amplitude reduction of waviness in elastohydrodynamic lubrication using an Eyring fluid model

This paper presents a first extension of the amplitude reduction approach, where the deformation of harmonic components of the roughness is considered, to non-Newtonian elastohydrodynamic lubrication (EHL) line contact. The amplitude reduction of one-sided waviness is computed as a function of the slide-roll ratio. Non-Newtonian effects result in an increase in the deformation for positive slide-roll ratios. This contrasts with published results using a Newtonian fluid where the deformation decreased for such conditions. Moreover, the amplitude reduction varies significantly throughout the contact, requiring an additional parameter for the characterization of the amplitude reduction. An explanation of these differences based on the velocity profile of the lubricant inside the contact concludes the paper

Short communication: Cystic fibrosis “factor(s)”: Present also in sera of shwachman’s pancreatic insufficiency

Using an in vivo closed-loop technique in rat jejunum, we have confirmed previous in vitro studies that cystic fibrosis (CF) serum inhibits water, sodium, and glucose absorption and transmural potential difference. CF heterozygote serum or sera from children with diarrhoeal disorders not associated with exocrine pancreatic insufficiency had no effect on transport. Sera from patients with Shwachman’s syndrome and exocrine pancreatic insufficiency had identical effects to CF serum. These results challenge the specificity of the CF “factor.”. Speculation: PANCREATIC-RELATED FACTORS The pancreas may modulate small intestinal absorption of water, electrolytes, and glucose via an humoral pathway. In exocrine pancreatic insufficiency, there could.be a deficiency of a normal serum factor which stimulates absorption or, alternatively, a factor which inhibits absorption could be present. © 1981 International Pediatric Research Foundation, Inc