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1.
Laryngoscope Investigative Otolaryngology ; JOUR: 1,
Article in English | Academic Search Complete | ID: covidwho-2085078

ABSTRACT

Objectives Methods Results Conclusion Level of evidence Dysfunction in smell or taste is well recognized phenomenon in patients infected with SARS‐CoV‐2. This study aimed to quantify the incidence and associated co‐morbidities of reported olfactory or gustatory dysfunction in patients who tested positive for SARS‐CoV‐2.From March 23, 2020 through July 31, 2020, 192,683 patients were tested for SARS‐CoV‐2 at Mayo Clinic. These patients with a positive test were contacted via telephone by physicians at Mayo Clinic and information gathered on patient demographics, comorbidities, symptoms and clinical risk stratification based on these factors.Two thousand two hundred and fifty patients tested positive for SARS‐CoV‐2 (1.2%). Six hundred and sixty‐seven (29.6%) of these patients reported loss of smell or taste. Factors found to be correlated with reporting loss of smell or taste on multivariate analysis were: younger age, female sex, or symptoms of chest pain or tightness, cough, or headache and lower clinical risk category. Coronary artery disease (CAD) was associated with not reporting loss of taste or smell.Of 2250 patients testing positive for SARS‐CoV‐2 at Mayo Clinic, 667 reported loss of taste and smell. Patients who reported loss of smell or taste were younger, female and more likely to report cough, chest pain, headache, or history of chronic obstructive pulmonary disease (COPD), but overall had fewer high‐risk comorbidities. Those who were older, male, and a reported history of CAD were less likely to report chemosensory dysfunction. Our data are the largest single institution data reporting COVID‐19 associated loss of smell or taste, and the first to associate COPD and CAD as factors that affect rates of reported chemosensory dysfunction.IIB. [ FROM AUTHOR]

2.
Laryngoscope Investigative Otolaryngology ; JOUR
Article in English | Web of Science | ID: covidwho-2085077

ABSTRACT

Objectives Dysfunction in smell or taste is well recognized phenomenon in patients infected with SARS-CoV-2. This study aimed to quantify the incidence and associated co-morbidities of reported olfactory or gustatory dysfunction in patients who tested positive for SARS-CoV-2. Methods From March 23, 2020 through July 31, 2020, 192,683 patients were tested for SARS-CoV-2 at Mayo Clinic. These patients with a positive test were contacted via telephone by physicians at Mayo Clinic and information gathered on patient demographics, comorbidities, symptoms and clinical risk stratification based on these factors. Results Two thousand two hundred and fifty patients tested positive for SARS-CoV-2 (1.2%). Six hundred and sixty-seven (29.6%) of these patients reported loss of smell or taste. Factors found to be correlated with reporting loss of smell or taste on multivariate analysis were: younger age, female sex, or symptoms of chest pain or tightness, cough, or headache and lower clinical risk category. Coronary artery disease (CAD) was associated with not reporting loss of taste or smell. Conclusion Of 2250 patients testing positive for SARS-CoV-2 at Mayo Clinic, 667 reported loss of taste and smell. Patients who reported loss of smell or taste were younger, female and more likely to report cough, chest pain, headache, or history of chronic obstructive pulmonary disease (COPD), but overall had fewer high-risk comorbidities. Those who were older, male, and a reported history of CAD were less likely to report chemosensory dysfunction. Our data are the largest single institution data reporting COVID-19 associated loss of smell or taste, and the first to associate COPD and CAD as factors that affect rates of reported chemosensory dysfunction. Level of evidence IIB.

3.
Otolaryngology - Head and Neck Surgery ; 167(1 Supplement):P287, 2022.
Article in English | EMBASE | ID: covidwho-2064409

ABSTRACT

Introduction: To limit the spread of COVID-19 and keep faculty and applicants safe, many otolaryngology subspecialties conducted their fellowship interviews via a virtual format, including within the field of rhinology. Given the novel virtual format of interviews during the 2021 rhinology interview cycle, our study looked to determine how virtual interviews compared with in-person interviews from the perspective of rhinology fellowship directors. Method(s): A web-based anonymous survey was developed consisting of 15 questions. Electronic letters were sent to all fellowship directors participating in the 2021 rhinology match requesting their participation. Fourteen of the 15 questions from our survey were based on a 5-point Likert-type scale, with 1 representing strong disagree and 5 representing strongly agree;there was 1 one open-ended question. Result(s): Overall, 70% of rhinology fellowship directors responded. Fellowship directors were divided on whether they were satisfied with the virtual interview but overall felt the process was convenient (74%). Most (74%) reported that virtual interviews did not allow them to sufficiently display their program. In addition, 70% felt that the virtual interview process did not allow them to establish rapport with applicants and also to determine who would be the best fit for their program (70%). Most also reported placing more emphasis on applicants' curriculum vitae and letters of recommendation. Overall, 65% said they would not plan to offer virtual interviews in the future despite similar or better match results. Conclusion(s): While virtual interviews result in notable cost reductions and increased convenience to programs and applicants, fellowship directors were mixed in their level of satisfaction with the overall process. This was primarily related to the perceived inability to accurately reflect their program remotely and also an increased difficulty evaluating applicants via a virtual format. These limitations led to most fellowship directors not planning to offer virtual interviews in the future despite similar match results to when conducting traditional interviews.

4.
American Journal of Transplantation ; 22(Supplement 3):598-599, 2022.
Article in English | EMBASE | ID: covidwho-2063361

ABSTRACT

Purpose: Therapies for COVID-19 in immunocompromised (IC) patients (pts), including transplant (tx) pts, are limited. We describe our experience with ALVR109, an allogeneic, partially HLA-matched T-cell product, given through emergency investigational new drug (eIND) application to 4 consecutive IC pts with protracted COVID-19. Method(s): To measure SARS-CoV-2 viral loads, SARS-2 RNA was quantified by RT-PCR (N gene) in plasma and saliva. ALVR109 was manufactured for Allovir at Baylor College of Medicine. Result(s): Between May and October 2021, ALVR109 was given to 4 IC pts with COVID-19 (details in Table 1). 2 pts had lymphoma (1 post auto-tx) and 2 had lung tx. All pts had SARS-CoV-2 RNA detected in plasma (viremia) in the weeks leading up to ALVR109 administration. Infusions (20-40 million cells (MC) per dose) were well-tolerated with no adverse events. Prior to ALVR109, pts 1 and 3 had progressive COVID-19 and ongoing SARS-CoV-2 viremia despite monoclonal antibodies (mABs) and remdesivir. Following ALVR109 administration both patients had a decrease in viremia with marked clinical improvement in pt 1, but both eventually died from their underlying disease. Viral loads (plasma/saliva) and functional scores for pt 1 are shown in the figure. Autopsy of pt 3 showed no evidence of SARS-CoV-2 infection by lung in-situ hybridization (ISH). Pts 2 and 4 received ALVR109 as adjunctive therapy to mABs and remdesivir;viremia continued to decline following ALVR109 and both pts survived and were discharged home. Conclusion(s): This initial experience suggests a potential role of ALVR109 in the treatment of IC and tx pts with COVID-19. SARS-CoV-2-specific T-cells appear to be safe and may control viremia in IC pts. Larger studies are needed to confirm this observation, define the best candidates for ALVR109, and determine optimal timing of administration. (Table Presented).

5.
Canadian Journal of Nonprofit and Social Economy Research ; 12(S1):91-96, 2021.
Article in English | Scopus | ID: covidwho-2030595

ABSTRACT

When the COVID-19 pandemic hit Canada in March 2020, charitable and nonprofit sector leaders quickly realized the survival of many organizations was at risk. Three national coalitions formed to seek support for the sector from the federal government. Their efforts produced several concrete policy outcomes, including the inclusion of charities and nonprofits in all major federal relief programs and two support programs designed for charities and nonprofits. They also contributed to significantly increased awareness among policymakers of the role and challenges of charities and nonprofits. This has opened a policy window that the sector can use to advance several long-standing goals. © 2021, University of Alberta Library. All rights reserved.

6.
JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING ; 49:S16-S16, 2022.
Article in English | Web of Science | ID: covidwho-1935150
7.
Journalism Practice ; 2022.
Article in English | Scopus | ID: covidwho-1890692

ABSTRACT

Local journalism is a pillar of democratic societies, and its role becomes more critical during crises. But despite its critical importance, local news has faced immense challenges that jeopardize its sustainability in the U.S. This study examines the Colorado media ecology by comparing local news sources across four different counties during Summer 2020 and exploring the factors behind similarities and differences in coverage. Building on Napoli et al.’s (2017) framework to assessing the health of local news, the study uses content analysis to examine original, local reporting and coverage of critical information needs as well as type of framing in over 600 online stories appearing on the home pages of all news sources in the four counties. The findings reveal that the Colorado journalism ecosystem post-Covid outpaces U.S. local news in quality in the pre-Covid era yet aligns with disturbing trends pointing to inequities and disparities. In other words, rural, poorer, and more racially and ethnically diverse Colorado communities tend to have weaker news ecosystems and are more likely to become news deserts. The study also introduces thematic coverage as a necessary dimension to add to journalism quality assessment frameworks and discusses several approaches to salvage local news. © 2022 Informa UK Limited, trading as Taylor & Francis Group.

8.
Ann Oncol ; 33(8): 836-844, 2022 08.
Article in English | MEDLINE | ID: covidwho-1885609

ABSTRACT

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.


Subject(s)
COVID-19 , Neoplasms , COVID-19/epidemiology , Humans , Medical Oncology , Neoplasms/epidemiology , Neoplasms/therapy , Pandemics , Prospective Studies
9.
American Journal of Respiratory and Critical Care Medicine ; 205:1, 2022.
Article in English | English Web of Science | ID: covidwho-1879990
10.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-338066

ABSTRACT

The single dose Ad.26.COV.2 (Janssen) vaccine elicits lower levels of neutralizing antibodies and shows more limited efficacy in protection against infection than either of the available mRNA vaccines. In addition, the Ad.26.COV.2 has been less effective in protection against severe disease during the Omicron surge. Here, we examined the memory B cell response to single dose Ad.26.COV.2 vaccination. Compared to mRNA vaccines, Ad.26.COV.2 recipients had significantly lower numbers of RBD-specific memory B cells 1.5 or 6 months after vaccination. Memory antibodies elicited by both vaccine types show comparable neutralizing potency against SARS-CoV-2 and Delta. However, the number of memory cells producing Omicron neutralizing antibodies was somewhat lower after Ad.26.COV.2 than mRNA vaccination. The data help explain why boosting Ad.26.COV.2 vaccine recipients with mRNA vaccines is effective, and why the Janssen vaccine appears to have been less protective against severe disease during the Omicron surge than the mRNA vaccine.

11.
Media Studies: Texts, Production, Context, Third Edition ; : 1-548, 2021.
Article in English | Scopus | ID: covidwho-1875984

ABSTRACT

This thoroughly revised and updated third edition provides a comprehensive introduction to the various approaches to the field, explaining why media messages matter, how media businesses prosper and why media is integral to defining contemporary life. The text is divided into three parts – Media texts and meanings;Producing media;and Media and social contexts –  exploring the ways in which various media forms make meaning;are produced and regulated;and how society, culture and history are defined by such forms. Encouraging students to actively engage in media research and analysis, each chapter seeks to guide readers through key questions and ideas in order to empower them to develop their own scholarship, expertise and investigations of the media worlds in which we live. Fully updated to reflect the contemporary media environment, the third edition includes new case studies covering topics such as Brexit, podcasts, Love Island, Captain Marvel, Black Lives Matter, Netflix, data politics, the Kardashians, President Trump, ‘fake news’, the post-Covid world and perspectives on global media forms. This is an essential introduction for undergraduate and postgraduate students of media studies, cultural studies, communication studies, film studies, the sociology of the media and popular culture. © 2022 Paul Long, Beth Johnson, Shana MacDonald and Schem Rogerson Bader.

12.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333557

ABSTRACT

A spike protein mutation D614G became dominant in SARS-CoV-2 during the COVID-19 pandemic. However, the mutational impact on viral spread and vaccine efficacy remains to be defined. Here we engineer the D614G mutation in the SARS-CoV-2 USA-WA1/2020 strain and characterize its effect on viral replication, pathogenesis, and antibody neutralization. The D614G mutation significantly enhances SARS-CoV-2 replication on human lung epithelial cells and primary human airway tissues, through an improved infectivity of virions with the spike receptor-binding domain in an "up" conformation for binding to ACE2 receptor. Hamsters infected with D614 or G614 variants developed similar levels of weight loss. However, the G614 virus produced higher infectious titers in the nasal washes and trachea, but not lungs, than the D614 virus. The hamster results confirm clinical evidence that the D614G mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increases transmission. For antibody neutralization, sera from D614 virus-infected hamsters consistently exhibit higher neutralization titers against G614 virus than those against D614 virus, indicating that (i) the mutation may not reduce the ability of vaccines in clinical trials to protect against COVID-19 and (ii) therapeutic antibodies should be tested against the circulating G614 virus before clinical development. IMPORTANCE: Understanding the evolution of SARS-CoV-2 during the COVID-19 pandemic is essential for disease control and prevention. A spike protein mutation D614G emerged and became dominant soon after the pandemic started. By engineering the D614G mutation into an authentic wild-type SARS-CoV-2 strain, we demonstrate the importance of this mutation to (i) enhanced viral replication on human lung epithelial cells and primary human airway tissues, (ii) improved viral fitness in the upper airway of infected hamsters, and (iii) increased susceptibility to neutralization. Together with clinical findings, our work underscores the importance of this mutation in viral spread, vaccine efficacy, and antibody therapy.

13.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333556

ABSTRACT

SARS-CoV-2 has resulted in a global pandemic and shutdown economies around the world. Sequence analysis indicates that the novel coronavirus (CoV) has an insertion of a furin cleavage site (PRRAR) in its spike protein. Absent in other group 2B CoVs, the insertion may be a key factor in the replication and virulence of SARS-CoV-2. To explore this question, we generated a SARS-CoV-2 mutant lacking the furin cleavage site (DELTAPRRA) in the spike protein. This mutant virus replicated with faster kinetics and improved fitness in Vero E6 cells. The mutant virus also had reduced spike protein processing as compared to wild-type SARS-CoV-2. In contrast, the DELTAPRRA had reduced replication in Calu3 cells, a human respiratory cell line, and had attenuated disease in a hamster pathogenesis model. Despite the reduced disease, the DELTAPRRA mutant offered robust protection from SARS-CoV-2 rechallenge. Importantly, plaque reduction neutralization tests (PRNT 50 ) with COVID-19 patient sera and monoclonal antibodies against the receptor-binding domain found a shift, with the mutant virus resulting in consistently reduced PRNT 50 titers. Together, these results demonstrate a critical role for the furin cleavage site insertion in SARS-CoV-2 replication and pathogenesis. In addition, these findings illustrate the importance of this insertion in evaluating neutralization and other downstream SARS-CoV-2 assays. IMPORTANCE: As COVID-19 has impacted the world, understanding how SARS-CoV-2 replicates and causes virulence offers potential pathways to disrupt its disease. By removing the furin cleavage site, we demonstrate the importance of this insertion to SARS-CoV-2 replication and pathogenesis. In addition, the findings with Vero cells indicate the likelihood of cell culture adaptations in virus stocks that can influence reagent generation and interpretation of a wide range of data including neutralization and drug efficacy. Overall, our work highlights the importance of this key motif in SARS-CoV-2 infection and pathogenesis. ARTICLE SUMMARY: A deletion of the furin cleavage site in SARS-CoV-2 amplifies replication in Vero cells, but attenuates replication in respiratory cells and pathogenesis in vivo. Loss of the furin site also reduces susceptibility to neutralization in vitro .

14.
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-332321

ABSTRACT

While SARS-CoV-2 continues to adapt for human infection and transmission, genetic variation outside of the spike gene remains largely unexplored. This study investigates a highly variable region at residues 203-205 in the SARS-CoV-2 nucleocapsid protein. Recreating a mutation found in the alpha and omicron variants in an early pandemic (WA-1) background, we find that the R203K+G204R mutation is sufficient to enhance replication, fitness, and pathogenesis of SARS-CoV-2. The R203K+G204R mutant corresponds with increased viral RNA and protein both in vitro and in vivo . Importantly, the R203K+G204R mutation increases nucleocapsid phosphorylation and confers resistance to inhibition of the GSK-3 kinase, providing a molecular basis for increased virus replication. Notably, analogous alanine substitutions at positions 203+204 also increase SARS-CoV-2 replication and augment phosphorylation, suggesting that infection is enhanced through ablation of the ancestral 'RG' motif. Overall, these results demonstrate that variant mutations outside spike are key components in SARS-CoV-2's continued adaptation to human infection. Author Summary: Since its emergence, SARS-CoV-2 has continued to adapt for human infection resulting in the emergence of variants with unique genetic profiles. Most studies of genetic variation have focused on spike, the target of currently available vaccines, leaving the importance of variation elsewhere understudied. Here, we characterize a highly variable motif at residues 203-205 in nucleocapsid. Recreating the prominent nucleocapsid R203K+G204R mutation in an early pandemic background, we show that this mutation is alone sufficient to enhance SARS-CoV-2 replication and pathogenesis. We also link augmentation of SARS-CoV-2 infection by the R203K+G204R mutation to its modulation of nucleocapsid phosphorylation. Finally, we characterize an analogous alanine double substitution at positions 203-204. This mutant was found to mimic R203K+G204R, suggesting augmentation of infection occurs by disrupting the ancestral sequence. Together, our findings illustrate that mutations outside of spike are key components of SARS-CoV-2's adaptation to human infection.

15.
Annals of Emergency Medicine ; 78(4):S86, 2021.
Article in English | EMBASE | ID: covidwho-1734173

ABSTRACT

Study Objectives: Amid the US opioid epidemic, emergency providers and patients are searching for non-opioid or nonpharmacologic pain treatment options. The challenge of managing pain without opioids was escalated by the COVID-19 pandemic with opioid related overdoses and deaths increasing by 20-40%. Most healthcare professionals have limited knowledge, resources or time for pain education, especially in the emergency department (ED). To address these needs a novel pain coaching program was designed including a menu of nonpharmacologic patient discharge toolkit materials. Study objectives were to determine descriptive patient and toolkit utilization data and challenges in the first 4 months of a novel pain program. Methods: Target population consisted of patients ≥14 years of age seen by a new ED Pain Coaching staff from January 4, 2021- April 30, 2021. The two ED sites consisted of an urban, academic center with trauma center, pediatric ED, etc. and an affiliated community ED. Patients were determined by ED rounding, ED census review and consultation by ED staff, physicians, physical therapy, palliative care and pharmacy. Summary statistics for patient demographics, pain type, REALM-SF score, educational topics, toolkit materials, challenges and other data were ed from coaching and patient notes on a daily basis using a REDCap database for analysis. Upon request, there were select inpatient and repeat coaching encounters. Results: During this 4-month pilot, 296 coaching sessions were completed on 276 unique patients;20 screen outs for severe pain, procedures, violent behavior or other obstacles. Average age was 43 with 85% between 20-70 years of age;62% female;60% African American. Pain was 46% acute, 50% acute on chronic and 4% chronic with patients often having multiple pain etiologies: musculoskeletal (74%), inflammatory (71%), post-trauma (15%), headache (14%), post-surgical (4%) and neuropathic (3%). Education topics provided with accompanying toolkit items: hot/cold gel packs (90%), car with 4 flat tires analogy (90%), pain neuroscience education (88%), aromatherapy inhalers (82%), breathing techniques (69%), virtual reality (51%), exercise (38%), stretching (35%), diet (20%), acupressure (11%). The majority of patients were seen in 2 EDs or associated trauma center (87%);however, the coach received referrals for selected inpatients (13%). Seventeen educational brochures were made available to patients with aromatherapy, managing pain, pain and stress, and nonpharmacologic management being most utilized. Challenges to coaching included medical condition (14%), too much pain (11%), time constraints (7%);52% had no challenges. Regarding patient feedback, 61% indicated the session was helpful and 39% were unsure at the time. Conclusion: Results from this novel ED pain coach and discharge toolkit model provide valuable insights for development of a national pain coach model. Coaching scripts, note template, brochures, videos, inventory and other programmatic materials will be published for further implementation. Future plans include longitudinal patient follow-up, staff satisfaction assessment and addition of new modalities.

16.
Abhigyan ; 39(2):28-36, 2021.
Article in English | ProQuest Central | ID: covidwho-1710978

ABSTRACT

Employability has today become a major problem due to the Covid-19 pandemic. The purpose of this paper is to explore the theoretical concepts and models of employability to ascertain the gap between knowledge and skill imparted by various educational and training institutes and its absorption. The literature review focuses on two aspects, i.e., the existing pre-Covid-19 literature and the emerging concepts of employability, post- Covid-19. Different approaches to employability, starting from the studies by Gazier (1998), Hillage and Pollard (1999) to later ones like 'organisation approach', employability in terms of individual transferable skills, career management, perceived employability, etc.have been analysed. Literature related to the emerging concept of employability post-Covid-19 are focused more on competency, career resilience, learning with experience /problem based learning, innovation and creativity, adaptability and sustainability. An employability framework has been developed and proposed based on the Four Quadrant Model of Human Knowledge by Ken Wilber.

17.
2021 ASEE Virtual Annual Conference, ASEE 2021 ; 2021.
Article in English | Scopus | ID: covidwho-1695894

ABSTRACT

Students' experiential learning in out-of-class involvements encompasses a significant part of their engagement and professional development in college. The covid-19 pandemic has challenged the delivery of these experiential learning opportunities, requiring student affairs professionals to significantly adapt their programming to continue serving students in ways that accommodate social distancing guidelines, in-person event capacity limits, and remote participants. While research has investigated online learning in classroom contexts, less is known about the implications of a virtual learning environment on engagement in experiential learning. This study addresses the following research question: How are student affairs professionals adapting their programs and services to support student engagement in response to the covid pandemic? This study captures how student affairs professionals at a large Midwestern research university have adjusted programming and engagement efforts to maintain key elements of experiential learning in hybrid and remote learning contexts, where students' engagement ranges from entirely on-line to various combinations of partial in-person and online participation. The Midwestern university transitioned from predominantly residential to fully online during the spring 2020 semester and then allowed students to choose whether to continue fully online or return to campus for a hybrid learning environment in the fall 2020 semester. This study draws on Schlossberg's transition theory to examine how student affairs professionals transitioned programs and services in the 2020-2021 academic year to respond to the covid-19 pandemic and the associated changing safety guidelines. Facing unique challenges in this varied, constantly changing environment, student affairs professionals described three key elements of successful program and service adaptations: (1) a focus on student needs, (2) collaboration across student support units, and (3) creativity and innovation in approaches to engage students. Through thematic analysis of interviews with 13 student affairs professionals (including student organization advisors and administrators, student programming coordinators, and student support specialists), research findings provide further insight into the challenges and opportunities presented in adapting experiential learning to hybrid and remote formats. Research findings will help inform ongoing efforts to craft hybrid and remote student programming and services that support and engage students in these unprecedented times. These findings can also inform the development of student support programs for the growing body of online students in higher education. © American Society for Engineering Education, 2021

18.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326830

ABSTRACT

The furin cleavage site (FCS), an unusual feature in the SARS-CoV-2 spike protein, has been spotlighted as a factor key to facilitating infection and pathogenesis by increasing spike processing 1,2. Similarly, the QTQTN motif directly upstream of the FCS is also an unusual feature for group 2B coronaviruses (CoVs). The QTQTN deletion has consistently been observed in in vitro cultured virus stocks and some clinical isolates 3. To determine whether the QTQTN motif is critical to SARS-CoV-2 replication and pathogenesis, we generated a mutant deleting the QTQTN motif (ΔQTQTN). Here we report that the QTQTN deletion attenuates viral replication in respiratory cells in vitro and attenuates disease in vivo. The deletion results in a shortened, more rigid peptide loop that contains the FCS, and is less accessible to host proteases, such as TMPRSS2. Thus, the deletion reduced the efficiency of spike processing and attenuates SARS-CoV-2 infection. Importantly, the QTQTN motif also contains residues that are glycosylated4, and disruption its glycosylation also attenuates virus replication in a TMPRSS2-dependent manner. Together, our results reveal that three aspects of the S1/S2 cleavage site – the FCS, loop length, and glycosylation – are required for efficient SARS-CoV-2 replication and pathogenesis.

19.
Information Services and Use ; 41(1-2):131-136, 2021.
Article in English | Scopus | ID: covidwho-1626556

ABSTRACT

During the “NISO update” session at the NISO Plus 2021 conference, which took place online due to the COVID-19 pandemic, members of the KBART (Knowledge Base and Related Tools) Standing Committee presented their plans and work toward KBART Phase III, a revision of the KBART Recommended Practice. In an interactive breakout session, they sought input from attendees on how KBART is being used and what new content types it should support. Presenters from the KBART Standing Committee were Noah Levin (Independent Professional), Stephanie Doellinger (OCLC, Inc.), Robert Heaton (Utah State University), and Andrée Rathemacher (University of Rhode Island). Assisting them in preparing the presentation were Jason Friedman (Canadian Research Knowledge Network), Sheri Meares (EBSCO Information Services), Benjamin Johnson (ProQuest), Elif Eryilmaz-Sigwarth (Springer Nature), and Nettie Lagace (NISO). © 2021 - The authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC 4.0).

20.
Blood ; 138:476, 2021.
Article in English | EMBASE | ID: covidwho-1582425

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic that has taken millions of lives around the globe. Treatment of patients with moderate and severe COVID-19 disease has included dexamethasone, tocilizumab, Remdesivir, convalescent plasma, and targeted antibodies, however, currently, there are no FDA approved targeted cellular therapies in the treatment of mild or moderate SARS-CoV-2 disease. Virus-specific cytotoxic T cell lymphocytes (vCTLs) have shown therapeutic efficacy in immunocompromised patients with viral infections. We developed a multicenter and multidisciplinary Viral Cytotoxic T-Cell Consortium (VIRCTLC) to investigate the use of vCTLs manufactured by direct enrichment using the Cytokine Capture System (CCS) on the CliniMACS® Prodigy device. SARS-CoV-2 specific PepTivator Peptides consist of overlapping peptides that span the entire sequence of the protein (Protein N and M), or the length of its immunodominant domain (Protein S). The peptides can bind to either MHC class I or MHC class II molecules and are therefore able to target both CD4 and CD8 T cells. Objective: To screen, manufacture, and characterize SARS-CoV-2 vCTLs generated from convalescent COVID-19 donors using the CliniMACS® Cytokine Capture System on the CliniMACS® Prodigy device. Methods: Donor screening was done utilizing PBMNCs from 15 convalescent COVID-19 donors after informed consent. PBMNCs were stimulated with a mix of PepTivator peptides (Miltenyi Biotech®) contained in the S, M and N proteins. IFN-γ levels were examined in CD3, CD4, and CD8 T cells by flow cytometry analysis. After informed consent, PBMNCs from three convalescent COVID-19 donors who screened positively to the PepTivator® peptide pools of SARS-CoV-2 Proteins M, N and S were collected by apheresis using the SPECTRA Optia® apheresis instrument. PBMNCs were incubated with the PepTivator® peptide pools for 4 hours. After incubation, the SARS-CoV-2 vCTLs were enriched using the CliniMACS Cytokine Capture System as we have previously described (Flower/Cairo, et al, ASTCT, 2020). Samples were taken from the enriched vCTLs and tested in gram stains, sterility cultures, cell counts, viability and IFN-γ cytokine staining (CD3/CD4/CD8/IFN-γ marker panel) by flow cytometry. Amplification and sequencing of TCRβ CDR3 regions of pre-stimulated PBMNC, stimulated PBMNCs samples taken from the QC bag (QC samples) and the enriched SARS-CoV-2 vCTLs were performed on the ImmunoSEQ platform using ImmunoSEQ® TCRB Assay kit (Adaptive Biotechnologies, Seattle, WA, USA). Characterization of immune subsets was done by mass cytometry analysis with 41 Immunophenotypic markers. Transcriptome of the immune landscape of QC samples, and enriched vCTLs was compared with the pre samples using the human nCounter PanCancer Immune Profiling Panel on the nCounter system. Results: We demonstrate that 93.3% of convalescent donor blood samples passed the screening criteria for clinical manufacture. Three validation runs resulted in enriched T cells that consisted of 79% + 21% (mean + SEM) IFNγ + T cells (Fig.1). TCRβ sequencing showed that convalescent COVID-19 donors have a highly diverse TCR repertoire and we identified TCRβ CDR3 clones that are known to be associated with SARS-CoV-2 T cell responses. Immunophenotyping analysis demonstrated more CD4 T cells than CD8 T cells in the SARS CoV-2 vCTLs, an increase in memory CD8 and CD4 cells, especially CD8 T EM, CD4 T cm and CD4 T EMRA cells (Fig.2) and an increase DC cells in the SARS CoV-2 vCTL products as compared to pre-stimulated PBMNCs. Expression of the exhaustion markers was not enhanced in the SARS CoV-2 vCTLs as compared to pre-stimulated PBMNCs. Transcriptome analysis showed increased gene expression in T-cell function, interleukin, pathogen defense, and TNF superfamily pathway genes in the SARS CoV-2 vCTLs as compared to pre-stimulated PBMNCs. Conclusion: Our study demonstrates that highly functional SARS-CoV-2 vCTLs can be rapidly generat d by direct cytokine enrichment from convalescent donor peripheral blood mononuclear cells. These data serve as pre-clinical validation for an ongoing clinical trial utilizing related HLA-matched and haplo-identical SARS CoV-2 vCTLs for the treatment of patients with mild and moderate SARS-CoV-2 disease (IND #27260, NCT# 04896606). [Formula presented] Disclosures: Lee: Kiadis Pharma: Divested equity in a private or publicly-traded company in the past 24 months, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding;Courier Therapeutics: Current holder of individual stocks in a privately-held company. Johnson: Miltenyi Biotec: Research Funding. Cairo: Jazz Pharmaceutical: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Amgen: Speakers Bureau;Sanofi: Speakers Bureau;Servier: Speakers Bureau;Sobi: Speakers Bureau;Omeros: Membership on an entity's Board of Directors or advisory committees;Nektar: Membership on an entity's Board of Directors or advisory committees.

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