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1.
American Journal of Transplantation ; 22(Supplement 3):570, 2022.
Article in English | EMBASE | ID: covidwho-2063350

ABSTRACT

Purpose: Data shows COVID vaccine response after 2 doses in patients on Belatacept immunosuppression (IS) is low, with reported rates of seroconversion (as measured by COVID spike IgG antibody (IgG Ab) detection) of <10%. It is suggested that T cell immunity provides more nuanced marker of immunity. We seek to describe immune response with third dose of vaccine using T cell immunity and spike Ab as surrogate markers. Method(s): 12 kidney transplant patients on long term belatacept maintenance therapy were included. All patients received induction rabbit anti thymocyte globulin at transplant and were maintained on triple IS with mycophenolate and steroids. All patients received 3 doses of the Pfizer BioNTech SARS CoV2 mRNA vaccine. IgG Ab and T cell immunity response were monitored after 2 doses of vaccine, on the date of 3rd dose with repeat testing done about 4 weeks after 3rd dose. Due to small sample size, T cell response detection was treated qualitatively as "detected" and "negative" results based upon manufacturer instructions (Eurofins Viracor). IgG Ab response was treated qualitatively as "detected" and "negative", as many responses were too low to be reliably quantifiable. Result(s): Of the 12 included patients, 58% were female, 50% were African American, at mean of 77 months post transplant. After 2 vaccine doses, immunity was detected using the T cell based assay in 6/12 [50.0%, 95% CI: (21.1%-78.9%)];after 3 doses, T cell immunity detection remained the same (6/12). After 2 doses, IgG was detected in 2/12 patients [16.7%, 95% CI: (2.1%-48.4%)]. After 3 doses, this rate doubled to 4/12 [33.3%, 95% CI: (9.9%-65.1%)]. All IgG Ab detected patients were within the T Cell detected patients. There were statistically significant differences between patients that showed a response vs those that did not although patients with no response had been on a numerically higher duration of belatacept (mean=56 months) vs those with any response (mean=34 months;p=0.23). No patients developed a COVID 19 infection during the study period. Conclusion(s): In this cohort, T cell response identified a bigger subset of patients with vaccine response with 2 mRNA vaccine doses compared with those identified with an IgG response only. However, both T cell immunity and IgG Ab response remained low after 2 or 3 doses, and no patient in in the 2 dose group developed new T cell immunity response after third vaccination. IgG Ab response increased in half of the patients, but these were patients who already had developed a T cell immune response after second dose of vaccine. Total change in COVID spike IgG response after the third dose was up to 33% from an initial 16%, which may demonstrate improved total response to 3 doses. Further research is needed to assess if response rates improve with additional (fourth) doses of COVID vaccine or 'mix and match' strategies.

2.
Innovation in Aging ; 5:1019-1019, 2021.
Article in English | Web of Science | ID: covidwho-2012899
3.
Journal of General Internal Medicine ; 37:S339-S340, 2022.
Article in English | EMBASE | ID: covidwho-1995737

ABSTRACT

BACKGROUND: The impact of SARS-CoV-2 infection on intrinsic myocardial conduction continues to be an area of focus amongst the medical community. Our objective was to investigate if specific myocardial conduction abnormalities were independently associated with mortality in patients hospitalized with COVID 19. METHODS: Under IRB exemption, the electronic medical records of COVID-19 patients (N=3840) undergoing index hospitalization were reviewed to extract presentation ECG conduction data, demographics, and laboratory results (within 8h). This patient cohort was then separated into two groups based on mortality vs. not (N=520). Logistical regression was used to test association of ECG conduction intervals with mortality. RESULTS: According to our nominal logistic fit for hospital mortality, Heart Rate (HR) >100 (p=0.0007;LW 4.14), QRS duration > 120 ms (p=0.0053;LW 2.27), and QTc prolongation (defined as QTc > 450ms in males;QTc > 460ms in females) (p=0.0089;LW 2.04) were independently associated with higher risk of mortality. LogWorth (LW) calculations were included in an effort to estimate the proportional effect each variable has on overall mortality. LW > 2 were shown to be statistically significant with p< 0.05 with HR > 100 (LW 4.14) having the highest proportional effect on mortality followed by QRSd (LW 2.27) then QTc prolongation (LW 2.04). PR interval> 200ms (p=0.30) and QRS axis (p=0.15) were not associated with higher risk of mortality. CONCLUSIONS: Amongst our patient cohort, HR > 100, QRSd > 120ms, and QTc prolongation (QTc > 450 in males;QTc > 460 in females) were each independently associated with higher risk of mortality in patients hospitalized with COVID 19. These findings support the use of objective ECG data in risk stratifying patients hospitalized with COVID 19.

4.
Philos Trans A Math Phys Eng Sci ; 380(2233): 20210308, 2022 Oct 03.
Article in English | MEDLINE | ID: covidwho-1992465

ABSTRACT

During infectious disease outbreaks, inference of summary statistics characterizing transmission is essential for planning interventions. An important metric is the time-dependent reproduction number (Rt), which represents the expected number of secondary cases generated by each infected individual over the course of their infectious period. The value of Rt varies during an outbreak due to factors such as varying population immunity and changes to interventions, including those that affect individuals' contact networks. While it is possible to estimate a single population-wide Rt, this may belie differences in transmission between subgroups within the population. Here, we explore the effects of this heterogeneity on Rt estimates. Specifically, we consider two groups of infected hosts: those infected outside the local population (imported cases), and those infected locally (local cases). We use a Bayesian approach to estimate Rt, made available for others to use via an online tool, that accounts for differences in the onwards transmission risk from individuals in these groups. Using COVID-19 data from different regions worldwide, we show that different assumptions about the relative transmission risk between imported and local cases affect Rt estimates significantly, with implications for interventions. This highlights the need to collect data during outbreaks describing heterogeneities in transmission between different infected hosts, and to account for these heterogeneities in methods used to estimate Rt. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.


Subject(s)
COVID-19 , Bayes Theorem , COVID-19/epidemiology , Disease Outbreaks , Humans , Reproduction , Time
5.
Journal of Paediatrics and Child Health ; 58(SUPPL 2):109-110, 2022.
Article in English | EMBASE | ID: covidwho-1916230

ABSTRACT

Background: Shared decision-making (SDM) involves patients in making decisions about their care, informed by clinical evidence and patient values and preferences. Despite its importance to woman-centred care, effectively implemented SDM remains uncommon in maternity care. This project developed clinician SDM training to help reduce variation in planned birth (labour induction/elective Caesarean), and pilottested acceptability and feasibility. Methods: An online SDM clinician training intervention package was developed in 2020-2021 by a Sydney-based team including midwifery and medical maternity clinicians, consumers, and social scientists. The package included a preparatory online video and a two-hour practical workshop (converted to online due to COVID-19) where participants rotate roles (woman, clinician, observer/rater) in clinical scenarios devised to test SDM in planned birth. Participants completed online pre- and posttraining surveys. Results: Preliminary results (first workshop Oct 2021;second scheduled March 2022) suggest clinicians agree that SDM is easy to understand, facilitate and experiment with, compatible with current practices, enable women to make more informed decisions compared with the usual approach and produce more benefit than harm. There were mixed responses about whether SDM is better than or involves major changes to current practice, will help women make choices that align with their values, or enable partnership between women and clinicians. Conclusions: The SDM training program has potential to improve clinicians' capacity for engaging woman in decisions about their care around planned birth and its timing. Further workshops, qualitative interviews with participants and a posttraining consumer survey at each site is planned for 2022.

6.
TUNING JOURNAL FOR HIGHER EDUCATION ; 9(2):529-561, 2022.
Article in English | Web of Science | ID: covidwho-1912425

ABSTRACT

The COVID-19 pandemic created the need for a global change in tertiary education. Universities that traditionally relied on contact with students in physical classrooms were forced to consider modes of remote teaching to mitigate the risks of infection due to physical proximity. This study evaluates the emergency remote teaching implemented within the Department of Information Technology at the Durban University of Technology, South Africa. An emergency remote teaching model with four stages consisting of: preparation, synchronous and asynchronous teaching and learning, e-assessments and reflections are described, analysed and evaluated with reference to both lecturers and students. The evaluation is performed using both qualitative and quantitative research methods. Qualitative analysis was performed on 29 sources using content analysis. 229 initial codes were identified and first categorized into 13 subcategories and finally to the four categories synonymous with the adopted four-stage emergency remote teaching model: preparation (135 references), asynchronous and synchronous teaching and learning (67 references), e-assessments (25 references) and reflections (8 references). Quantitative data on the use of the learning management system from 2019 to 2020 evaluated the results of the applied changes in practice. From the results, it was evident that students and lecturers invested much time in the learning management system with 13 tools being adopted by the 49 analysed subjects. The learning management system was used extensively for communication, assessment and dissemination of subject content. The comparative results of the data from the 2019 and 2020 academic years showed that the majority of the 2020 subjects' final results were statistically higher than the 2019 results. Results of analysis revealed the success of the implementation of the four-stage emergency remote teaching model.

7.
Journal of Sound and Music in Games ; 2(1):70-76, 2021.
Article in English | Scopus | ID: covidwho-1892391

ABSTRACT

The North American Conference on Video GameMusic (NACVGM) has been held yearly as an in-person conference. NACVGM 2020 was originally scheduled to occur in April 2020 in Ithaca, New York. As a result of the COVID-19 pandemic, many academic events in 2020 were shifted online, including game music conferences like Ludo2020 and NACVGM. The organizing committee for NACVGM decided to hold the full conference digitally as a live event. After hosting NACVGM2020 live on his personal Twitch.tv page, Ryan Thompson explains the technical means that made it possible and offers a series of recommendations for other individuals considering shifting in-person meetings to online events. This reflection provides one perspective on hosting an academic conference during lockdown. © 2021 Cultural Imperialism in Capcom’s Mega Man Series. All rights reserved.

8.
Journal of Urology ; 207(SUPPL 5):e169, 2022.
Article in English | EMBASE | ID: covidwho-1886483

ABSTRACT

INTRODUCTION AND OBJECTIVE: Nephrectomy and venous thrombectomy is a challenging procedure with potential morbidity and mortality. Despite the increasing use of immune checkpoint inhibitors (ICI) in the management of advanced renal cell carcinoma (RCC), data regarding the outcomes of venous thrombectomy following ICI is limited. We evaluated the feasibility and perioperative outcomes of nephrectomy and venous thrombectomy following ICIs. METHODS: Patients with locally advanced or metastatic RCC with venous thrombus undergoing nephrectomy following ICI therapy were evaluated in four high-volume US academic centers between June 2017 and June 2021. Clinical data, perioperative outcomes, and 90-day complications were recorded. RESULTS: Out of 79 patients who received post-ICI nephrectomy, 27 had venous thrombus. Median (IQR) age was 64 (55-71) years. ICI regimens were Nivolumab ± Ipilimumab (n=19), and Pembrolizumab± Axitinib (n=8). Nephrectomy was indicated following either a good clinical response to ICI (n=24) or as a palliative surgery (n=3). Venous thrombi levels are shown in Table-1. Among all patients, 26 (96%) underwent radical and 1 (4%) partial nephrectomy;12 (44.5%) open, 12 (44.5%) robotic and 3 (11%) laparoscopic. One robotic case converted electively to open. Vascular procedures included renal vein thrombectomy (n=6), IVC thrombectomy and primary repair (n=19), IVC patch repair (n=1), and suprarenal cavectomy (n=1). No intraoperative complications were reported. Nine patients showed no viable tumor in the thrombus, of whom 2 had complete response in the primary tumor as well (ypT0N0). 90-day complication rate was 33% (n=9), with 8 patients (30%) requiring readmission (Table-2). One death was reported within 90 days due to COVID-19 infection. CONCLUSIONS: Nephrectomy and venous thrombectomy following systemic immune checkpoint inhibitor therapy is feasible. One third of patients show no viable tumor in the thrombus. Larger studies are needed to predict pathological response.

12.
Fields Institute Communications ; 85:173-195, 2022.
Article in English | Scopus | ID: covidwho-1706211

ABSTRACT

Forecasting when an epidemic wave is likely to end is an important component of disease management, allowing deployment of limited control resources to be planned efficiently. Here, we report an analysis that we conducted in real-time during the first COVID-19 epidemic wave in mainland China. We developed a mathematical model to construct bounds on the end date of the first epidemic wave there, assuming that strong quarantine and testing measures remained in place until the epidemic wave was confirmed over. We used reported data on case numbers in China from January 20 to April 9, 2020. We first developed an analytic approach, obtaining a formula describing the probability distribution of the epidemic wave end date using a combination of deterministic modelling and the theory of continuous-time Markov processes. Then, we ran simulations of an individual-based model to demonstrate that our analytic predictions were accurate. We found that the predicted end date of the first epidemic wave in China depended on the proportion of infected individuals that are symptomatic and appear in case notification data, as opposed to remaining asymptomatic throughout their courses of infection. We therefore provide an easy-to-use approach for predicting the ends of epidemic waves, as well as a clear demonstration that predicted end-of-epidemic times depend on the extent of asymptomatic infection. Our framework can be applied to predict the ends of epidemic waves during future outbreaks of a wide range of pathogens. © 2022, Springer Nature Switzerland AG.

13.
Advances in Mental Health ; : 13, 2022.
Article in English | Web of Science | ID: covidwho-1704006

ABSTRACT

Objective: To explore emergent values for community-based peer support in three projects and use of peer research methodology. Background: Peer support refers to the support people with shared lived experiences provide to each other. Its roots are in the civil rights movement, providing alternatives to clinical treatments. This method of support is delivered in different settings, with varying degrees of structure. In this paper, it includes shared experience of mental health issues. Methods: We reviewed interview data from two evaluations and one development project - mental health (n = 69), women-only (n = 40), and maternal mental health (n = 24), respectively. Each project used peer research methods. Peer support values from each project were compared, along with reflections from mostly peer researchers who worked on them (n = 11). Results: Six peer support values emerged and were found to be identifiable and applicable in different contexts. Decisions on facilitation and leadership varied across projects and generated some concerns over professionalisation, including non-peer leadership. Frameworks were viewed as broadly useful, but peer support is heterogenous, and peer researchers were concerned about over-rigid application of guidance. Discussion: We propose caution applying frameworks for peer support. Values must remain flexible and peer-led, evolving in new contexts such as COVID-19. Evaluators have a responsibility to consider any potentially negative consequences of their work and mitigate them. This means ensuring research outputs are useful to the peer support community, and knowledge production is based upon methodologies, such as peer research, that complement and are consistent with the values of peer support itself.

14.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326964

ABSTRACT

HLA is a critical component of the viral antigen presentation pathway. We investigated the relationship between severity of SARS-CoV-2 disease and HLA type in 3,235 individuals with confirmed SARS-CoV-2 infection. We found only the DPB1 locus to be associated with the binary outcome of whether an individual developed any COVID-19 symptoms. The number of peptides predicted to bind to an HLA allele had no significant relationship with disease severity both when stratifying individuals by ancestry or age and in a pooled analysis. Age, BMI, asthma status, and autoimmune disorder status were predictive of severity across multiple age and individual ancestry stratificiations. Overall, at the population level, we found HLA type is significantly less predictive of COVID-19 disease severity than certain demographic factors and clinical comorbidities.

15.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-326616

ABSTRACT

The SARS-CoV-2 spike protein (S) is the sole viral protein responsible for both viral binding to a host cell and the membrane fusion event needed for cell entry. In addition to facilitating fusion needed for viral entry, S can also drive cell-cell fusion, a pathogenic effect observed in the lungs of SARS-CoV-2 infected patients. While several studies have investigated S requirements involved in viral particle entry, examination of S stability and factors involved in S cell-cell fusion remain limited. We demonstrate that S must be processed at the S1/S2 border in order to mediate cell-cell fusion, and that mutations at potential cleavage sites within the S2 subunit alter S processing at the S1/S2 border, thus preventing cell-cell fusion. We also identify residues within the internal fusion peptide and the cytoplasmic tail that modulate S cell-cell fusion. Additionally, we examine S stability and protein cleavage kinetics in a variety of mammalian cell lines, including a bat cell line related to the likely reservoir species for SARS-CoV-2, and provide evidence that proteolytic processing alters the stability of the S trimer. This work therefore offers insight into S stability, proteolytic processing, and factors that mediate S cell-cell fusion, all of which help give a more comprehensive understanding of this highly sought-after therapeutic target.

16.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-326578

ABSTRACT

Drug repurposing is the only method capable of delivering treatments on the shortened time-scale required for patients afflicted with lung disease arising from SARS-CoV-2 infection. Mucin-1 (MUC1), a membrane-bound molecule expressed on the apical surfaces of most mucosal epithelial cells, is a biochemical marker whose elevated levels predict the development of acute lung injury (ALI) and respiratory distress syndrome (ARDS), and correlate with poor clinical outcomes. In response to the pandemic spread of SARS-CoV-2, we took advantage of a high content screen of 3,713 compounds at different stages of clinical development to identify FDA-approved compounds that reduce MUC1 protein abundance. Our screen identified Fostamatinib (R788), an inhibitor of spleen tyrosine kinase (SYK) approved for the treatment of chronic immune thrombocytopenia, as a repurposing candidate for the treatment of ALI. In vivo , Fostamatinib reduced MUC1 abundance in lung epithelial cells in a mouse model of ALI. In vitro , SYK inhibition by Fostamatinib promoted MUC1 removal from the cell surface. Our work reveals Fostamatinib as a repurposing drug candidate for ALI and provides the rationale for rapidly standing up clinical trials to test Fostamatinib efficacy in patients with COVID-19 lung injury.

17.
SSM Qual Res Health ; 2: 100027, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1592050

ABSTRACT

Emerging evidence suggests that sex workers face unique and profound risks arising from the COVID-19 pandemic. To illuminate the pandemic's effects on sex worker health and safety and identify intervention opportunities, from May-August 2020 in-depth interviews were conducted with a purposive sample of 15 sex workers, four service providers and two individuals who were both. Sampled sex workers included eight people of color, eight cisgender women, five cisgender men, three non-binary people, and one transgender woman. Using Conservation of Resources Theory to define impacts on sex worker resources and resulting health and safety implications, a deductive thematic analysis was conducted. Seven resources were threatened due to the pandemic: work opportunity, sex work venues, social support, health services, money, food, and housing. The loss of these resources was exacerbated by stigma - notably sex work criminalization - and significantly undermined health and safety by increasing food and housing instability, increasing risks of violence, and diminishing safer sex negotiation. Six resources were activated in response: social support, digital skills, health knowledge, non-sex work employment, money, and resilience. While social support had numerous benefits, investing digital skills and non-sex work employment were generally of limited impact. The pandemic's negative health and safety effects were most profound at the intersections of race, gender, class, and migration status. These findings suggest sex workers need urgent and ongoing support, with investments in social support and sex work decriminalization likely to have the greatest effects on health and safety relative to and beyond the COVID-19 pandemic.

19.
Front Vet Sci ; 8: 662198, 2021.
Article in English | MEDLINE | ID: covidwho-1526801

ABSTRACT

The abrupt and life-altering shifts brought on by the COVID-19 pandemic have stimulated research in fields ranging from social sciences to virology. This study explored perceptions and experiences of COVID-19's impact on students at Lincoln Memorial University-College of Veterinary Medicine (LMU-CVM) and considered how to respond to these. Semistructured interviews were conducted with 20 students from LMU-CVM. Thematic analysis elucidated five subthemes that were combined into two main themes based on Bertuccio's framework of grief in response to uncertainty distress. Uncertainty and disruption of routine were subthemes of ambiguous loss, while lost opportunities, milestones missed, and risk concern came under anticipatory grief. There was overlap and fluidity within these themes, with frustration, stress, and unexpected benefits pervading all categories. Differences were noted between classes, with clinical students expressing concern over graduation and lack of preparedness, and preclinical students with online assessment, lost opportunities for clinical experiences, and the loss of social connections. These results point to mitigation strategies for the adverse effects of COVID-19-related stressors specific to this population that encompass academic, physical, and mental well-being concerns. Clear communication, assurance of quality education, flexibility for meeting family needs, financial assistance, and mental health support are the areas evident from the interviews where successful responses might be targeted. This study also highlights areas for future research, including follow-up interviews, given the prolonged timeline of COVID-19, surveys of beliefs and practices across a larger university population, and exploration of the long-term impact on academic and practice success of the affected cohorts.

20.
Urology Practice ; 8(4):472-478, 2021.
Article in English | Web of Science | ID: covidwho-1511135

ABSTRACT

Introduction: We aimed to determine criteria of interest to urology residency program directors when selecting applicants for residency interviews during the COVID-19 pandemic. Methods: An anonymous survey was sent via email to all urology residency program directors across the United States. Program directors were asked to assign the degree of importance (1-5, with 5 being very important) of selected factors in deciding which applicants to interview. Surveys were distributed and study data were managed using REDCap. Descriptive statistical analyses were performed. Results: In total, 130 urology residency program directors were contacted and 64 (49.3%) responded to the survey. Urology letter(s) of recommendation based on nonvirtual rotation(s), urology clerkship grades, research experience, and visa status of the applicant were cited as the most important factors in selecting applicants for interview with median importance ratings of 5, 4, 4, and 5, respectively. Urology letter(s) of recommendation based on virtual rotation(s), virtual subinternship(s), and participation in social media activities were the least important in selecting applicants for interviews with median importance ratings of 2 for each. Notably, urology letter(s) of recommendation based on nonvirtual rotation(s) and visa status were consistently ranked as the most important factors by more than 50% of program directors. Conclusions: Urology program directors value urology letter(s) of recommendation from non-virtual rotation(s), urology clerkship grades, research experience, and applicant visa status as the most important factors in selecting applicants for interviews during the COVID-19 pandemic. Virtual rotation( s) and social media activity were ranked the lowest among criteria that influence the selection process for interviews.

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