Inflammation profiling and recovery clusters five months post-hospitalisation for COVID-19

Background Understanding the underlying mechanisms of post-COVID sequelae (Long COVID) is urgently needed to guide interventions. Aim To compare the inflammation profiles of four recovery clusters post-hospitalisation. Methods Post-Hospitalisation COVID-19 (PHOSP-COVID) is a prospective, multi-centre study across UK. Four recovery clusters previously identified using clinical data (symptoms, mental health, cognitive impairment, and physical function) at 5 months post-discharge were used based on severity of on-going health impairments: very severe, severe, moderate (cognitive), and mild. Inflammatory profiling performed from plasma samples using the Olink Explore 384 inflammation panel. Multinomial logistic regression for each protein was undertaken comparing the mild cluster with each of the remaining clusters with FDR of 0.1 to adjust p values. Results 626 participants (clusters: very severe n=111, severe n=173, moderate/cognitive n=73 and mild n=269). Proteomic results from 296 proteins were included. After adjustment for age, BMI, and comorbidity count, 13 proteins were significantly elevated in the very severe cluster, and 2 proteins in the moderate/cognitive cluster, compared to the mild cluster (Figure 1). Conclusion Inflammatory mediators consistent with persistent lung and systemic inflammation were associated with the severity of ongoing health impairments highlighting potential therapeutic pathways to be tested.

Trauma and digital media: Introduction to crosscurrents special section

Associations between trauma and media theory are longstanding, going back at least to Walter Benjamin's observations on technology and modernity, which were themselves informed by Freud's 1920 speculations on war trauma following WWI. A century later, and in the wake of numerous conflicts, catastrophes, and far-reaching technological transformations—and of course the COVID pandemic—it is time to reconsider the relation between trauma and media, digital platforms in particular. While some significant scholarship has noted the intersections of modern media technologies such as photography, film, radio, television, and recently digital and algorithmic media, with the conception and experience of trauma, a more systematic theoretical consideration of the relation between media and trauma remains to be developed. And with the intensifying reliance on new and old media in these pandemic times the question of these relations is increasingly urgent. Moving beyond conceptions of media as representing or inducing trauma, this special section of Crosscurrents explores how (digital) media and trauma shape one another. © The Author(s) 2022.

Investigating the experience of professional carers supporting individuals with intellectual disability who were at risk of admission – a qualitative study

Purpose: This study aims to understand the experiences of professional paid carers providing community support to people with intellectual disability "at risk of admission”. This study explores factors that were helpful or lacking in terms of the support the carers received from NHS health services during this time. Design/methodology/approach: This study conducted semi-structured interview with eight participants. Thematic analysis was used to analyse the data. Findings: Three main themes and ten subthemes were identified. The first main theme was "support systems” that were available or lacking for the client and their carers. The second main theme was "training and supervision” available to the carers and their team when the individual they supported needed additional support. The third theme was "change” clients encountered which included changes in the environment as well as changes because of COVID-19 pandemic. Originality/value: To the best of the authors' knowledge, this is the first study on experiences of carers during specifically high stress periods, such as when the clients they are supporting are at risk of hospital admission. © 2022, Emerald Publishing Limited.

Tackling a post-COVID-19 cholecystectomy waiting list, are we meeting the challenge?

Background: The COVID-19 pandemic has led to a tremendous backlog in elective surgical activity, with over six million people on waiting lists and only 64% of patients meeting the 18-week elective standard. Our Hospital Trust adopted an innovative approach to dealing with elective waiting times for cholecystectomy during the recovery phase from COVID-19. This study aimed to evaluate trends in overall cholecystectomy activity and the effect on waiting times. Method(s): A prospective observational study was undertaken investigating patients who received a cholecystectomy at large UK hospital Trust, between February 2021 and February 2022. There were multiple phased strategies to tackle a 533 patient waiting list: Private sector, multiple sites including emergency operating, mobile theatre, and seven-day working. An additional 364 patients were added and 145 removed, for multiple reasons, from the list during the study period. Correlation of determination (R2) and Kruskal-Wallis analysis were used to evaluate trends in waiting times across the study period. Result(s): 657 patients underwent a procedure, of which 628 (95.6%) were completed electively. The median age was 49 years, 602 (91.6%) patients had an ASA of 1-2, and 494 (75.2%) were female. Thirty (4.6%) patients were listed post gallstone pancreatitis, 380 (57.8%) for cholelithiasis, and 228 (34.7%) for cholecystitis. The median length of stay was zero days (IQR 0-1), with 30-day complication (C-D >=3, 1.8%), readmission (3.0%) and mortality (0.0%) rates noted. The current waiting list includes 95 patients, with median waiting times reduced from 428 days (IQR 373-508) to 49 (IQR 34-96), R2=0.654, p<0.001. For pancreatitis specifically, waiting times have dropped from a median of 218 days (IQR 139-239) to 28 (IQR 24-40), R2=0.613, p<0.001. Conclusion(s):We have safely and effectively tackled the cholecystectomy waiting list locally utilising a number of phased strategies. Significant progress is being made towards once again meeting the gold-standard target for gallstone pancreatitis patients. The approach utilised here has potential to be adapted to other units, or other operation types in order to reduce elective waiting times.We have safely and effectively tackled the cholecystectomy waiting list locally utilising a number of phased strategies. Significant progress is being made towards once again meeting the gold-standard target for gallstone pancreatitis patients. The approach utilised here has potential to be adapted to other units, or other operation types in order to reduce elective waiting times.

Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.

BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors. METHOD: Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change. RESULTS: Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status. CONCLUSIONS: We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.

A bacterial extracellular vesicle-based intranasal vaccine against SARS-CoV-2 protects against disease and elicits neutralizing antibodies to wild-type and Delta variants.

Several vaccines have been introduced to combat the coronavirus infectious disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current SARS-CoV-2 vaccines include mRNA-containing lipid nanoparticles or adenoviral vectors that encode the SARS-CoV-2 Spike (S) protein of SARS-CoV-2, inactivated virus, or protein subunits. Despite growing success in worldwide vaccination efforts, additional capabilities may be needed in the future to address issues such as stability and storage requirements, need for vaccine boosters, desirability of different routes of administration, and emergence of SARS-CoV-2 variants such as the Delta variant. Here, we present a novel, well-characterized SARS-CoV-2 vaccine candidate based on extracellular vesicles (EVs) of Salmonella typhimurium that are decorated with the mammalian cell culture-derived Spike receptor-binding domain (RBD). RBD-conjugated outer membrane vesicles (RBD-OMVs) were used to immunize the golden Syrian hamster (Mesocricetus auratus) model of COVID-19. Intranasal immunization resulted in high titres of blood anti-RBD IgG as well as detectable mucosal responses. Neutralizing antibody activity against wild-type and Delta variants was evident in all vaccinated subjects. Upon challenge with live virus, hamsters immunized with RBD-OMV, but not animals immunized with unconjugated OMVs or a vehicle control, avoided body mass loss, had lower virus titres in bronchoalveolar lavage fluid, and experienced less severe lung pathology. Our results emphasize the value and versatility of OMV-based vaccine approaches.

Dynamic Approach to Pharmacovigilance in the COVID-19 Era: An International Journal of Medical Toxicology and Drug Experience

Background/Introduction: The clinical presentation and natural history of infection with the novel SARS-CoV-2 virus are relatively unknown, as are the risks associated with the infection and use of pharmaceutical agents. Objective/Aim: Adapt existing pharmacovigilance capabilities to ensure appropriate evaluation of the benefit-risk profiles of specific therapies during the ongoing pandemic. Methods: Bristol Myers Squibb (BMS) Epidemiology have created a tool to dynamically estimate background COVID-19 incidence rates by country, time-period, demographic categories, standards of care, and reporting practices. Local data were updated through the course of the pandemic with background rates re-estimated at regular intervals. Cases, severe cases, and deaths per 100,000 were rescaled to the age and geographic distribution of treated patients (in clinical programs or real-world use). Drug-specific Safety Management Teams used these background rates to identify potential COVID-19-related safety signals in investigational and marketed drugs. Real-world data sources were utilized to understand testing and treatment patterns. The BMS Clinical Safety Program (CSP), a systematic data collection capability, reduces reporting bias and further enhances our understanding of adverse events of interest through the development and implementation of event-specific, targeted case report forms (CRFs) within BMS interventional clinical trials. The COVID-19 CSP CRFs collect patient-level COVID-19 data (i.e., risk factors, diagnosis, clinical presentation, progression, treatment, and outcomes). Results: To date, we have not identified signals of increased risk related to COVID-19 infection that warrant additional action for any of our treatments. TriNetX COVID-19 Rapid Response Network data (February 2021) showed that among 250,000 patients with cancer, positivity rates were similar across immunotherapy (2.5%), chemotherapy (2.7%), and hormone therapy (2.5%). Explorys data showed a shift in median nivolumab treatment frequency from Q2W to Q3W among 1,114 patients with negative COVID-19 tests and to Q4W among 129 COVID-19-positive patients continuing treatment. Conclusion: Individual case level findings and background incidence rates are mutually informative;remarkable or unexpected insights from one may prompt further analysis and validation from the other. Leveraging these complementary pharmacovigilance capabilities in parallel continues to provide a flexible and innovative means to identify potential safety signals, both quantitatively (epidemiology) and qualitatively (CSP), as the conditions of the pandemic evolve. The latest CSP adaptation has included incorporation of CRF data points focused on COVID-19 vaccination and its impact. Once sufficient CSP data are available, analysis will help us understand the impact of COVID-19 infections on the efficacy and safety of our investigational therapies and allow comparisons to real-world data.

Patient satisfaction with telehealth in fpmrs during the COVID-19 pandemic

Objective: SinceMarch 2020, the COVID-19 pandemic has catalyzed rapid integration of telemedicine services into clinical practice. Our primary aim was to assess patient satisfaction with telehealth care in Female Pelvic Medicine and Reconstructive Surgery (FPMRS). Our secondary aim was to assess patient access to technology for telehealth visits. Methods: This was an IRB-approved, single-institution, survey study of a convenience sample of patients presenting for telehealth visits within the Division of FPMRS from July 22, 2020 to January 15, 2021. We invited new and established patients to complete a single survey regarding reason for visit, overall satisfaction, access to technology, previous use of telemedicine, and preference for future visits. We present data as mean ± standard deviation or proportion. Results: Of 227 patients offered the survey, 142 (62.6%) responded;84 (59.2%) completed the survey following a video visit, and 58 (40.9%) completed the survey following a telephone visit. Respondents had a mean age of 51.5 ± 15.4 years, and most were Non-Hispanic White (70.4%) and had at least a Bachelor's degree (64.8%). The most common primary diagnoses were sexual dysfunction (26.1%), overactive bladder (21.8%), and urinary incontinence (14.1%). Most patients in both the video and phone groups were completely satisfied (62.4% and 56.0%, respectively) or moderately satisfied (24.4% and 39.3%, respectively). Patient-reported advantages of telehealth included saving travel time (93.0%), waiting room time (59.2%), parking fees (50.0%), time off work (43.7%), and public transit fees (22.5%). Patients also reported greater overall convenience (60.6%) and feeling that they had more time with the provider (21.8%). Patient-cited disadvantages were concern about the provider's ability to make a diagnosis (69.0%) or see something of concern remotely (64.1%). Only 5.6% of patients expressed concern about difficulty building rapport with a provider virtually. Regarding access to telehealth visits, 8.5% cited a poor internet connection and 7.0% felt that setting up a virtual platform could be challenging. In anticipation of post-COVID FPMRS visits, most respondents (79.6%) preferred a combination of virtual and in-person visits. Only 2.1% indicated a preference for all future visits to be virtual, while 10.6% preferred only inperson visits, and 7.7% did not express a preference. Among respondents who preferred at least some virtual visits, 73.3% preferred video, whereas 25.9% preferred telephone visits. Conclusions: This study demonstrates high patient satisfaction with virtual telehealth visits at our FPMRS Division during the COVID-19 pandemic. Saving travel time and overall convenience were themost highly cited advantages of telehealth by patients. Patients prefer receiving a combination of telehealth and in-person visits post-pandemic. This study underscores an important role for telehealth in future FPMRS practice and should inform future studies to explore which conditions, visit types, and patient characteristics are best served by virtual versus in-person visits.

Nature engagement for human and nature's well-being during the Corona pandemic

Purpose To explore the associations between noticing nature, nature connectedness, time in nature and human and nature's well-being during the corona pandemic restrictions. Design/methodology/approach Natural England's people and nature survey (PANS) data (n = 4,206) from the UK was used to assess a number of well-being outcomes (loneliness, life satisfaction, worthwhile life and happiness) and pro-nature behaviours as a function of longer-term physical time in nature and psychological connectedness to nature and shorter-term visits and noticing of nature. Findings Longer-term factors of nature connectedness and time in nature were both consistent significant predictors of well-being measures (apart from loneliness) and pro-nature conservation behaviours. Considered alone short-term visits and noticing were again consistent and significant predictors of three well-being measures, but recent visits to nature were not associated with pro-nature conservation behaviours. A combined regression highlighted the importance of a longer-term relationship with nature in all outcomes apart from loneliness but also revealed that even when considered in concert with longer-term factors, currently noticing nature had a role in feeling one's life was worthwhile, pro-nature behaviours and loneliness. Originality/value The closeness of the human-nature relationship and noticing nature have rarely been examined in concert with nature visits. Further, the reciprocal benefits of pro-nature behaviours are often overlooked.

Diagnosis of COVID-19 by exhaled breath analysis using gas chromatography mass spectrometry

Background: A novel human coronavirus, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), emerged in China in late 2019 and has since claimed more than one million lives. COVID-19 infection is perceived to be seasonally recurrent and a rapid non-invasive biomarker to accurately diagnose patients early-on in their disease course will be necessary to meet the operational demands for COVID-19 control in the coming years.Objective: To evaluate the role of exhaled breath volatile breath biomarkers in identifying patients with suspected or confirmed COVID 19 infection, based on their underlying reverse transcriptase polymerase chain reaction (RT-PCR) status. Methods: We conducted an observational study at Glenfield Hospital, Leicester, United Kingdom, recruiting adult patients with suspected or confirmed COVID19 pneumonia. Breath samples were collected using a standard breath collection bag, modified with appropriate filters to comply with local infection control recommendations and samples were analysed using gas chromatography mass spectrometry (GC-MS).Findings: 81 patients were recruited, of whom 52/81 (64%) have subsequently tested positive for COVID19. A LASSO regression analysis, with the dependent variable as PCR status was run. A set of seven features were extracted that had non-zero regression coefficients in at least 70 out of 100 runs of 10-fold cross validation. Compound identities were confirmed using the Metabolomics Standards Initiative (MSI). These were benzaldehyde, 1-propanol (MSI level 1), 3,6-methylundecane (MSI level 2), camphene and beta-cubebene (MSI level 1 and 2 respectively). Iodobenzene was also extracted, likely of exogenous origin, and an unidentified compound. A logistic regression model was fitted with the dependent variable as PCR status and independent variables as the seven features selected by the LASSO model. Partial Least Squares Discriminant Analysis (PLSDA) and Principal Component Analysis (PCA) were applied to the seven features, with the dependent variable as PCR status. The AUC for the first discriminant function score was 0.836 (95% CI: 0.745-0.928), Sensitivity was 0.68 (95% CI 0.551-0.809), Specificity was 0.857 (95% CI 0.728-0.987), positive predictive value (PPV) was 0.895 (95% CI 0.797-0.992) and negative predictive value (NPV) was 0.6 (95% CI 0.448-0.752). The AUC for the first PCA was 0.799 (95% CI: 0.698-0.900), Sensitivity was 0.7 (95% CI 0.573-0.827), Specificity was 0.786 (95% CI 0.634-0.938), PPV was 0.854 (95% CI 0.745-0.962) and NPV was 0.595 (95% CI 0.436-0.753).Conclusions: breath analysis has promising combined sensitivity and specificity in detecting COVID19, raising the possibility of mass rapid testing, pending external validation of the identified biomarkers.

Invited Review: The spectrum of neuropathology in COVID-19.

There is increasing evidence that patients with Coronavirus disease 19 (COVID-19) present with neurological and psychiatric symptoms. Anosmia, hypogeusia, headache, nausea and altered consciousness are commonly described, although there are emerging clinical reports of more serious and specific conditions such as acute cerebrovascular accident, encephalitis and demyelinating disease. Whether these presentations are directly due to viral invasion of the central nervous system (CNS) or caused by indirect mechanisms has yet to be established. Neuropathological examination of brain tissue at autopsy will be essential to establish the neuro-invasive potential of the SARS-CoV-2 virus but, to date, there have been few detailed studies. The pathological changes in the brain probably represent a combination of direct cytopathic effects mediated by SARS-CoV-2 replication or indirect effects due to respiratory failure, injurious cytokine reaction, reduced immune response and cerebrovascular accidents induced by viral infection. Further large-scale molecular and cellular investigations are warranted to clarify the neuropathological correlates of the neurological and psychiatric features seen clinically in COVID-19. In this review, we summarize the current reports of neuropathological examination in COVID-19 patients, in addition to our own experience, and discuss their contribution to the understanding of CNS involvement in this disease.