SARS-CoV-2 Viral Clearance and Evolution Varies by Extent of Immunodeficiency (preprint)

Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged SARS-CoV-2 infection, but the immune defects that predispose to persistent COVID- 19 remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median time to nasal viral RNA and culture clearance in the severe hematologic malignancy/transplant group (S-HT) were 72 and 21 days, respectively, which were significantly longer than clearance rates in the severe autoimmune/B-cell deficient (S-A), non-severe, and non-immunocompromised groups (P<0.001). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and higher risk of developing antiviral treatment resistance. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral, while only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.

Impact of an online breathing and wellbeing programme (ENO Breathe)in people with persistent symptoms following COVID-19: a randomised controlled trial

Aims: ENO Breathe is an online breathing and wellbeing programme for people with Long COVID focusing on breathing re-training using singing techniques. Aim(s): to assess whether ENO Breathe improves health related quality-of-life (HRQoL) in people with persistent breathlessness following COVID-19. Method(s): A parallel-group, single-blind, RCT, comparing ENO Breathe(6 weeks) with usual care in adults, with persisting breathlessness +/- anxiety, following assessment at an NHS Long COVID clinic. Primary Outcome: change in HRQoL using the RAND SF-36 Mental(MHC) and Physical(PHC) Health Composite Scores. Secondary Outcomes: CAT, VAS for breathlessness (rest, walking, stairs, and running), Dysp-12, GAD-7. Participant experience was assessed using focus groups and free-text responses. Result(s): 150 participants (mean(SD) 49(12)years, 81% female, 320(127) days symptomatic;ENO Breathe(n=74), Control(n=76). ENO Breathe was associated with improvement in MHC of 2.42 points (95%CI 0.03 to 4.80, p=0.045), but not PHC 0.6 (-1.33 to 2.52, p=0.541). VAS breathlessness (running) favoured ENO Breathe -10.48(-17.23 to -3.73, p=0.003). Three participant experience themes were identified 1) improvements in symptoms;2) feeling that the programme was complementary to standard care;3) the particular suitability of singing and music to address their needs. Conclusion(s): An online breathing and wellbeing programme can improve the mental component of HRQoL and elements of breathlessness in people with persisting symptoms after COVID-19. Mind-body and music-based approaches, including practical, enjoyable symptom-management techniques may have a role supporting recovery.

Pathology Education Powered by Virtual and Digital Transformation: Now and the Future

[...]standing on the crest of yet another wave of change, driven by artificial intelligence (AI) and machine learning,2 pathology educators may soon be challenged to convey the best ways to apply these tools to the problems of diagnostic pathology for the coming generation of learners and the present corps of practitioners.3 Hence, this collaborative effort aims to describe the genetic code governing the transmission of pathology knowledge to subsequent generations of medical professionals.4 We aim to expose not just the code but also the supporting array of catalysts, enhancers, and other cofactors now in place to ensure we have a robust and potent supply of pathologists. APPLYING DP IN UNDERGRADUATE MEDICAL, DENTAL, VETERINARY, AND ALLIED HEALTH EDUCATION Beginning in 1985, this technology has been progressively more widely implemented in undergraduate medical, dental, veterinary, and allied health (nursing, pharmacy, medical technology, etc) education platforms in the United States and internationally.5,11-26 As noted above, virtual microscopy laboratories, available on personal devices or in school-based computer labs, have replaced fixed laboratories housing gross specimens, boxes of glass slides, and student microscopes. WSI with links to supplementary resources, such as gross and radiologic images and additional study material, provide enrichment for the teaching and learning experience in the new virtual environment. [...]significant exposure to microanatomy and the laboratory methods of pathology underpinning so much of diagnosis, therapy, and management is foundational.

The impact of the COVID-19 pandemic upon pancreatic cancer treatment (CONTACT Study): a UK national observational cohort study.

INTRODUCTION: CONTACT is a national multidisciplinary study assessing the impact of the COVID-19 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: The treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID-19 pandemic cohort (07/01/2019-03/03/2019) were compared to a cohort diagnosed during the first wave of the UK pandemic ('COVID' cohort, 16/03/2020-10/05/2020), with 12-month follow-up. RESULTS: Among 984 patients (pre-COVID: n = 483, COVID: n = 501), the COVID cohort was less likely to receive staging investigations other than CT scanning (29.5% vs. 37.2%, p = 0.010). Among patients treated with curative intent, there was a reduction in the proportion of patients recommended surgery (54.5% vs. 76.6%, p = 0.001) and increase in the proportion recommended upfront chemotherapy (45.5% vs. 23.4%, p = 0.002). Among patients on a non-curative pathway, fewer patients were recommended (47.4% vs. 57.3%, p = 0.004) or received palliative anti-cancer therapy (20.5% vs. 26.5%, p = 0.045). Ultimately, fewer patients in the COVID cohort underwent surgical resection (6.4% vs. 9.3%, p = 0.036), whilst more patients received no anti-cancer treatment (69.3% vs. 59.2% p = 0.009). Despite these differences, there was no difference in median overall survival between the COVID and pre-COVID cohorts, (3.5 (IQR 2.8-4.1) vs. 4.4 (IQR 3.6-5.2) months, p = 0.093). CONCLUSION: Pathways for patients with PDAC were significantly disrupted during the first wave of the COVID-19 pandemic, with fewer patients receiving standard treatments. However, no significant impact on survival was discerned.

COVID-19 and elite sport: Cardiovascular implications and return-to-play.

Curtailing elite sports during the coronavirus disease 2019 (COVID-19) pandemic was necessary to prevent widespread viral transmission. Now that elite sport and international competitions have been largely restored, there is still a need to devise appropriate screening and management pathways for athletes with a history of, or current, COVID-19 infection. These approaches should support the decision-making process of coaches, sports medicine practitioners and the athlete about the suitability to return to training and competition activities. In the absence of longitudinal data sets from athlete populations, the incidence of developing prolonged and debilitating symptoms (i.e., Long COVID) that affects a return to training and competition remains a challenge to sports and exercise scientists, sports medicine practitioners and clinical groups. As the world attempts to adjust toward 'living with COVID-19' the very nature of elite and international sporting competition poses a risk to athlete welfare that must be screened for and managed with bespoke protocols that consider the cardiovascular implications for performance.

Death, Funerals and Mourning on the Croatian Islands During the COVID-19 Pandemic

On islands and in island communities, especially smaller and more isolated ones, epidemics were often of greater intensity and left more significant consequences than on the mainland. The unique characteristics of an island (size, remoteness, isolation, small population size, and several manageable access points) affect the transmission of mainland epidemics and their frequency. The current global COVID-19 pandemic is an opportunity to investigate how the infection and epidemiological measures affected the life and death of island communities. The pandemic has brought mass death into our daily lives and altered the way people grieve, commemorate and remember their deceased. This paper presents the experiences and feelings of people during the COVID-19 pandemic on Croatian islands, with a focus on death, funer-als, mourning, and the loss of family members. Due to the impossibility of carrying out the usual practices related to the funeral because of COVID-19 restrictions, the process of mourning and dealing with the loss of loved ones was difficult. Island communities accepted the new rules and adapted to the new circumstances but indicated that island-specific and more flexible crisis management should be applied during this health crisis. Some epidemiological measures, such as social distancing, internal island travel restrictions, and reduced gatherings, were highlighted by islanders as challeng-ing and sometimes unnecessarily strict for some islands and their specific situations. For family members of those who died from COVID-19, additional factors and challenges have complicated their loss. Digital and social media were used to connect people and helped in coping with mourning in solitude and isolation. In this global pandemic, island communities responded to the impact of pandemic crises and adapted to new circumstances of the "new normal”. © 2022, Croatian Anthropological Society. All rights reserved.

Speaking of Online Learning: Alternative Practice-Based Learning Experiences for Speech Pathologists in Australia, Ghana and Hong Kong

Speech Pathology programs usually send students to workplaces to learn clinical skills necessary for practice. During COVID-19, programs needed to respond quickly to ensure that students continued to gain the necessary experiences and skills required to progress through their program and graduate as clinicians, while simultaneously complying with COVID-19 requirements. Case studies from seven different universities in Australia, Ghana and Hong Kong described the diverse ways in which placements were adapted to be COVID-safe, taking into account local needs. Some practices which had been included in placement education prior to the pandemic, such as telepractice and simulation-based learning, were extended and developed during this time. Educators, students, clinicians and clients responded to the rapidly changing needs of the time with flexibility and innovation, utilising a variety of technologies and tools to support case-based and virtual learning opportunities. Feedback from these diverse stakeholders about the experiences was positive, despite inevitable limitations and less-than-ideal circumstances. The positive findings provided insights for consideration in the future: could strategies implemented in response to the pandemic continue to be incorporated into placement experiences, enhancing current practices and maintaining student performance outcomes? Exceptional circumstances prompted exceptional responses;flexibility and innovation were accelerated in response to the pandemic and may transform future placement-based learning opportunities. © 2022 Jemma Skeat, Josephine Ohenewa Bampoe, Susan Booth, Emily Brogan, Maya Conway, Rachel Davenport, Simone Howells, Peggy Kan, Michelle Krahe, Sally Hewat, Abigail Lewis, Alex Little, Joanne Walters, Gwendalyn Webb, & Nikki Worthington. This Open Access article is distributed under the terms of the Creative Commons Attribution Attribution-Non-Commercial No Derivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited and is unaltered.

Teaching European History and Memory through the Eurovision Song Contest during the COVID-19 Pandemic

The Eurovision Song Contest (ESC) offers a unique snapshot of Europe, in which Europe invents itself anew with new artists and songs. The participating national media services, who are usually members of the European Broadcasting Union, create a new ‘usable past’ for themselves based on ‘presentist’ concerns (Olick, 2007, 19) with each iteration of the contest. The image of the present is hence dynamic, as is the image of the past that is recalled each year. The present performed at Eurovision is therefore always contingent on history, tradition and memory. This chapter explores how the ESC can serve as a vehicle for teaching history and memory to tertiary students by focusing on two countries and regions with histories of conflict with their European neighbours. The ESC can give voice to the desire for atonement in the case of a perpetrator nation such as Germany and to current concerns about acts of aggression from neighbouring powers in the case of Ukraine in 2016. In addition, the chapter discusses how the ESC can serve as a tool for teaching the politics of memory and the value of historical understanding in Europe through a pedagogical approach adopted during the global pandemic. © 2023 selection and editorial matter, Adam Dubin, Dean Vuletic and Antonio Obregón;individual chapters, the contributors.

The validity and reliability of the Breathing Vigilance Questionnaire (Breathe-VQ)

S13 Figure 1ConclusionThe Breathe-VQ is a valid and reliable tool to measure vigilance of breathing. Our data suggest that breathing vigilance may be a contributing factor in DB, and could represent a therapeutic target. Further research is now warranted using the Breathe-VQ in clinical populations of individuals with DB, chronic respiratory disease and COVID-19. Further research could assess the effects of breathing re-training, pulmonary rehabilitation and arts-in-health interventions on vigilance of breathing.

Evaluation of a state-wide effort to improve COVID-19 infection control in Massachusetts nursing homes.

BACKGROUND: During the deadly 2020 SARS-CoV-2 surge in nursing homes (NHs), Massachusetts (MA) initiated a multicomponent infection control intervention to mitigate its spread. METHODS: We aimed to assess the intervention's impact by comparing the weekly risk of PCR-confirmed infections among MA NH residents to those in neighboring New England states, all managed similarly by a single NH provider. We studied 2085 residents in 20 MA NHs and 4493 residents in 45 comparator facilities. The intervention included: (1) A 28-item infection control checklist of best practices, (2) incentive payments to NHs contingent on scoring ≥24 on the checklist, meeting 6 core competencies, testing residents and staff for SARS-COV-2 RNA, uploading data, and enabling virtual visits; (3) on-site and virtual infection control consultations for deficient facilities; (4) 6 weekly webinars; (5) continuous communication with the MA Department of Public Health; and (6) access to personal protective equipment, temporary staff, and SARS-CoV-2 testing. Weekly rates of infection were adjusted for county COVID-19 prevalence. RESULTS: The adjusted risk of infection started higher in MA, but declined more rapidly in its NHs compared to similarly managed facilities in other states. The decline in infection risk during the early intervention period was 53% greater in MA than in Comparator States (state-by-time interaction HR = 0.47; 95% CI 0.37-0.59). By the late intervention period, the risk of infection continued to decline in both groups, and the change from baseline in MA was marginally greater than that in the Comparator States (interaction HR 0.80; 95% CI 0.64-1.00). CONCLUSIONS: The MA NH intervention was associated with a more rapid reduction in the rate of SARS-CoV-2 infections compared to similarly managed NHs in neighboring states. Although several unmeasured factors may have confounded our results, implementation of the MA model may help rapidly reduce high rates of infection and prevent future COVID-19 surges in NHs.

Longitudinal SARS-CoV-2 Nucleocapsid Antibody Kinetics, Seroreversion, and Implications for Seroepidemiologic Studies.

Given widespread use of spike antibody in generating coronavirus disease vaccines, SARS-CoV-2 nucleocapsid antibodies are increasingly used to indicate previous infection in serologic surveys. However, longitudinal kinetics and seroreversion are poorly defined. We found substantial seroreversion of nucleocapsid total immunoglobulin, underscoring the need to account for seroreversion in seroepidemiologic studies.

The Association Between Social Determinants of Health and Postpartum Length of Stay During the COVID-19 Pandemic

INTRODUCTION: To determine differences in cesarean postpartum length of stay (pLOS) before and during the COVID-19 pandemic as a function of social determinants of health. METHODS: Cesarean birth pLOS data between January 1 and June 30, 2020, were reviewed. Births after March 10, 2020, were considered pandemic births. Primary outcome was early discharge <5,760 minutes (96 hours). Rates of early discharge were analyzed by social determinants of health, with socially vulnerable patients defined as Black or Hispanic, publicly insured, or non-English-speaking. We compared rates of early discharge before and during the pandemic overall and then among socially vulnerable patients using probit regression analysis. RESULTS: There were 1,885 eligible deliveries: 694 before the start of the pandemic and 1,171 after. Median pLOS pre-pandemic was 5,696 (IQR, 4,686-6,060) minutes versus 4,655 (IQR, 3,897- 5,860) minutes during the pandemic. Of the eligible deliveries, 54% had early discharges pre-pandemic compared to 71% afterwards (P<.01). Overall, we found these variables predictive of early discharge pLOS: socially vulnerable (P<.01), payer type (P<.01), English ability (P<.01), and multiparity (P<.01). Race as a variable alone was not found to be significantly predictive of early discharge. CONCLUSION: Socially vulnerable patients are more likely to leave the hospital earlier than their counterparts both before and during the COVID-19 pandemic. Our findings suggest that increased early discharges fall disproportionately on socially vulnerable patients. Further research is needed to determine whether these results are due to provider bias or patient driven.

Markers of Inflammation Predict PostThrombectomy Mortality in Acute Stroke

Objective: To further characterize the relationship between markers of inflammation and outcome in patients undergoing mechanical thrombectomy for acute stroke. Background: Inflammation and infection after ischemic stroke are known to exacerbate tissue injury and worsen clinical outcome. Thrombectomy has become standard of care in stroke, but little data exist regarding how inflammation affects outcome after thrombectomy. Design/Methods: We performed retrospective chart review of stroke patients who underwent mechanical thrombectomy at 2 tertiary academic centers between December 2018 and November 2020. The relationship between discharge mortality, admission WBC count, admission neutrophil percentage, peak WBC count, and fever (peak temperature >38°C) were analyzed using the Wilcoxon rank sum test, Student's t-test, and Fisher's exact test. Multivariable analysis was performed to test for independent predictors of discharge mortality. Analyses were performed for the entire cohort, then repeated in a cohort excluding COVIDpositive patients. Results: Of 254 patients who had thrombectomy for acute stroke, 42 (16.5%) died prior to discharge. Mortality was associated with admission WBC count (10.7 [8.9-14] vs. 8.6 [7-12], p=0.0064), admission neutrophil percentage (78% ± 11 vs. 70% ± 14, p=0.0001), peak WBC count (17 [13-22] vs. 12 [8.9-15], p<0.0001), and fever (71% vs. 29%, p<0.0001). In multivariable analysis, admission WBC count (OR 14, CI 1.5-158, p=0.024), neutrophil percentage (OR 1.04, CI 1.0-1.1, p=0.039), peak WBC count (OR 343, CI 27-5702, p<0.0001) and fever (OR 8.6, CI 3.6-23, p<0.0001) were significantly predictive of discharge mortality after controlling for age, admission NIHSS and post-thrombectomy ASPECTS score. Fifteen patients tested positive for COVID-19. In analyses excluding these patients, peak WBC count and fever remained independent predictors of discharge mortality. Conclusions: Elevated markers of inflammation during hospitalization predict discharge mortality in patients who undergo mechanical thrombectomy for acute stroke. Further study is warranted to investigate causation and identify opportunities to improve quality of care in this patient population.

Recovery from Disorders of Consciousness after Severe COVID-19

Objective: To examine long-term outcomes of disorders of consciousness (DoC) after severe COVID-19. Background: Some patients with severe COVID-19 experience persistently impaired arousal and/or awareness after discontinuation of sedation, consistent with DoC. In our recently published analysis of 21 such patients, 12 (57%) recovered to minimally conscious state (MCS) or better before hospital discharge. Recovery to MCS-especially within 8 weeks of injury-is an important prognostic indicator in DoC of other etiologies, but its significance in COVID-19 remains unknown. Design/Methods: All 21 patients were included in a prospectively followed cohort involving telephonic assessment 6 and 12 months after discharge. We examined relationships between recovery to MCS and survival. For patients completing telephone assessments, we report functional outcomes including Barthel Index, extended Glasgow Outcome Scale (E-GOS), and modified Rankin Scale (mRS);and psychological outcomes using Quality of Life in Neurological Disorders (Neuro-QOL) anxiety, depression, fatigue, and sleep disturbance inventories. Results: Recovery to MCS within 8 weeks of illness onset-but not later-was associated with 12-month survival (6/8 versus 2/9, p=0.024). Six patients completed both assessments. Of these, 2 were in DoC at 6 months and died by 12 months;1 recovered consciousness after 6 months but remained severely disabled;1 was moderately disabled;and 2 achieved functional independence (Barthel Index 100;E-GOS 5-7;mRS 1-2). Neuro-QOL scores were elevated at 6 but not 12 months. Conclusions: Ten percent (2/21) of our original cohort achieved functional independence by 12 months, demonstrating that recovery is possible after COVID-19-associated DoC. Consistent with the literature on non-COVID DoC, recovery to MCS within 8 weeks of illness onset may be prognostically favorable. Psychological symptoms in this severely ill group were less common than in patients with neurologic sequelae of COVID-19 generally. More work is needed to understand the natural history of long-term recovery from severe COVID-19.

Digital displacement of youth offending: addressing the issue

Purpose>Global evidence suggests a potential displacement of youth offending from the physical to the digital landscape, requiring revision of existing detection and intervention methods. This study aims to explore pathways from harmful to illegal online activity perpetrated by young people, legislation and police perspectives, current detection methods and interventions.Design/methodology/approach>This perspective paper examines issues observed within a larger systematic literature review on digital youth offending.Findings>A trajectory from acceptable to harmful and subsequently illegal behaviour was identified, with a particular pathway from unethical video game activity to digitally dependent offending. Legislation and police perspectives vary by jurisdiction, with a common theme that increased officer education is key to the level of preparedness to investigate cases. Machine learning and automatic prevention show promise as detection and disruption processes, with education recommended for young people as a deterrent and redirection of skills to positive outcomes.Research limitations/implications>Recommendations for further research include a broad survey of school students to include all identified areas of digital offending, which could drive the development of targeted education by law enforcement and partner agencies for young people.Practical implications>The shift in youth offending requires the justice and educational systems to adjust how they respond to youth crime. Policy and practise shifts can include further exploration of investigative hacking, education for law enforcement and educational prevention and redirection programmes aimed at youth.Originality/value>The digital displacement of youth offending is a progressively emerging concept. This paper examines the current state of response from educational and law enforcement agencies and discusses the next steps based on what is currently known.

Early Neurorehabilitation and Recovery from Disorders of Consciousness after Severe COVID-19: Findings from a Pilot Feasibility Study

Objective: Early neurorehabilitation improves outcomes in patients with disorders of consciousness after brain injury, but its applicability in COVID-19 is unknown. We demonstrate the feasibility of an early neurorehabilitation protocol for patients with COVID-19-associated disorders of consciousness in the intensive care unit (ICU) and evaluate factors associated with recovery. Methods: Between March 10 and May 20, 2020, we prospectively enrolled 21 ICU patients with delayed recovery of consciousness after severe COVID-19 in a pilot early neurorehabilitation protocol including serial Coma Recovery Scale - Revised (CRS-R) assessments and multimodal treatment. We retrospectively compared clinical features of patients who did and did not achieve a CRS-R total score (TS) ≥8, consistent with minimally conscious state, before discharge. We additionally present preliminary 6-month follow-up data for 8 patients who survived to discharge. Results: Patients underwent CRS-R a median of 6 (interquartile range [IQR] 3-10) times before discharge, beginning a median of 48 days (IQR 40-55) from admission. Twelve (57%) patients achieved at least one CRS-R TS ≥8, after a median of 8 days (IQR 2-14) off continuous sedation;they had lower body mass index (p = 0.009), lower peak serum C-reactive protein (p = 0.023), higher minimum arterial partial pressure of oxygen (p = 0.028) and earlier fentanyl discontinuation (p = 0.018). CRS-R scores fluctuated over time and best CRS-R TS was significantly higher than last CRS-R TS (median 8 [IQR 5- 23] vs 5 [IQR 3-18], p = 0.002). Earlier fentanyl (p = 0.001) and neuromuscular blockade (p = 0.015) discontinuation correlated with higher last CRS-R TS. Six-month follow-up data was obtained for 8 of 12 patients who survived to hospital discharge: of these, one patient (13%) had expired;3 (38%) remained in a disorder of consciousness;one (13%) was conscious but moderately disabled;and 3 (38%) achieved functional independence. Conclusion: It is feasible to provide early neurorehabilitation to patients with impaired consciousness after severe COVID-19 in the ICU. These patients can recover, but hypoxia, systemic inflammation, sedation and neuromuscular blockade may impact CRS-R scores and short-term outcomes. Return to functional independence is possible for some patients. Further research should evaluate factors influencing longer-term neurologic recovery and benefits of early rehabilitation in patients with severe COVID-19.