The Evolution of the Covid-19 Pandemic in Pediatric Patients with Sickle Cell Disease: From Alpha to Omicron

Background: Approximately two years ago, COVID-19 was declared a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and through genomic surveillance, we have seen the emergence of variants of SARS-CoV-2. In the United States, over 78 million cases and >900,000 deaths attributable to COVID-19 have been reported. SCD was identified as a risk factor for severe COVID-19 disease in adults and pediatric patients. The emergence of novel SARs- CoV-2 variants has led to challenges in diagnosis, treatment, and prediction of long-term sequelae in individuals with SCD and COVID-19. Aim(s): We compare the overall seasonal variation of COVID-19 variants and patterns of healthcare utilization and clinical presentation over time in pediatric patients with SCD and COVID-19 at Children's National Hospital (CNH). Method(s): Our single-center, observational cohort study included 193 pediatric patients with SCD (0-21 years) with PCR-confirmed SARSCoV- 2 infection between March 31, 2020, and January 31, 2022. Per the SECURE SCD Registry definitions, clinical severity was classified as asymptomatic, mild, moderate, and severe. Result(s): A total of 193 unique patients with SCD and positive SARS-CoV-2 PCRs between March 2020-January 2022 were included in our registry. Most patients were female (51.8%), and the mean age was 11.2 years (SD 6.5 years). Most of the cohort resides in Maryland (N=135), and HbSS was the dominant genotype (69.4%). During the alpha dominant variant of the COVID-19 pandemic (March 2020- June 2021) there were 70 cases, followed by 40 cases during the Delta variant (July 2021- December 19, 2021), and 83 cases during the Omicron variant dominance (from December 20, 2021-January 31,2022). There were 149 patients (77%) that presented to the emergency department (ED) or were hospitalized. There were a total of 80 hospitalizations (41.5%), and a relative comparison showed that the percentage of hospitalizations was highest during the delta wave (47.5%) and lowest during the omicron wave (36.1%) (p= 0.407). ED-only utilization was highest in the era of omicron (43.4%, N=36), followed by delta (32.5%, N=13), and then alpha (30%, N=21)(p=0.197). The most common SCD-related complication was vaso-occlusive (VOC) pain (33%, N=64) which accounted for half of all hospital admissions (51%, N=41 of 80). Acute chest syndrome (ACS) was reported in 40% (N=32) of admitted patients and was highest in the alpha era (54.8%, N=17). The use of blood transfusion therapy was highest in the alpha (N=17) and delta (N=14) variants, while Remdesivir use was highest in omicron (N=15). A total of 6 patients received monoclonal antibodies (Delta, N=4;omicron, N=2). Throughout all the variants, there was a significant difference in COVID-19 clinical severity (p>0.005). Of the patients classified as asymptomatic (13%, N=25), seventy-two percent (n=18) were diagnosed during the alpha variant. Mild severity was the most prevalent (69%, N=134), with the omicron variant having the highest cases (51.5%, N=69). Severe cases were observed in all variants (6.7%, N=13) but were most prevalent during the alpha variant (46.2%, N=6). Summary - Conclusion(s): Interestingly, while the relative percentage of hospitalizations was lowest during the omicron wave, it saw the highest percentages of ER utilization. Overall, COVID-19 remains mild in pediatric patients with SCD, and notably, there was higher health care utilization in the omicron era.

The emerald handbook of higher education in a post-covid world: New approaches and technologies for teaching and learning

Teaching and learning paradigms in higher education have been called into question by the COVID-19 pandemic, requiring new approaches, technologies, and resilience. The disruption caused to higher education operations prompted many to raise questions about HEI's adaptability and readiness to handle major disasters. Focussing particularly on developing countries in Africa and the Global South, The Emerald Handbook of Higher Education in a Post-Covid World emphasizes the urgent need to reform pedagogical models and the importance of recognizing and utilizing digital learning technologies, tools, and the power of the Internet to expand the range of teaching approaches, practices and learning interaction options in an age in which information communication technology and mobile devices have become commonplace in the daily life of students, academic leaders and HE practitioners. The contributors also address the importance of supporting the individual student in learning communities where they are separated by space, and safeguarding their social and emotional wellbeing as they engage and learn through mediated-communication-systems in an era of a fundamentally changed HE environment which will not completely return to previous models. Providing perspectives from contributors across multiple nations and settings, and written in a forthright, yet engaging manner, this volume is essential reading for higher education staff, researchers, and policy makers, to ensure higher education across the world is prepared to offer the best quality teaching and learning in the Covid and Post-Covid world. © 2022 Byron A. Brown and Alastair Irons. All rights reserved.

Teaching approaches, social support, and student learning in non-traditional classrooms in higher education

The literature on non-traditional classroom environments claims that the changed emphasis in higher education teaching from the lecturer to students has intensified the global focus on student-centred learning, prompting colleges and universities globally to introspect, re-examine, and re-structure their pedagogical approaches in an attempt to align with national educational policies, and to position themselves favourably with potential students in an increasingly competitive higher education environment. This is an environment that now relies heavily on digital learning technologies, which has provoked scholars such as Heick (2012) to perceive the change to the virtual as one that makes higher education institutions accessible from anywhere-in the cloud, at home, in the workplace, or restaurant. The COVID-19 crisis has reinforced the need for this flexibility. These forces have put universities and colleges under pressure to implement new teaching approaches in non-traditional classroom settings that are appropriate for, and responsive to, the COVID-19 crisis and students in terms of learning and social support. This chapter identified and appraised key teaching approaches. It is evident that there are three key teaching approaches that higher education institutions have adopted for delivering learning in an emergency and in a student-centred fashion. The three approaches, which include the time and place dispersion, transactional distance, and collaborative learning approaches, embrace social support because they are grounded in social constructivism. Academics need to be fully committed to the role of social support giving-that is, emotional, instrumental, informational, and appraisal support-in order to foster student wellbeing and cognitive development as students learn together but apart in nontraditional classrooms. The hurried manner in which teaching and learning practices in many higher education institutions have been moved to the online format has led academics to violate many key principles of the approaches they have adopted. And this situation is borne out in the case study discussed in Chapter 8 of this volume. A review of current remote teaching and learning practices is required if academics are to embrace the full principles of the approaches that are appropriate for teaching and learning in non-traditional classroom contexts. © 2022 by Byron A. Brown.

Reforming emergency remote teaching through the evaluation of practice in higher education

Emergency remote teaching is not the same as a systematic, carefully thought out, and designed online learning system. Emergency remote teaching is best perceived as merely a first step towards migrating into a fully fledged, and carefully designed, virtual or online mode of study. Notwithstanding, this chapter provides a theoretical explanation that justifies the relevance and importance of emergency remote teaching in higher education practice, in light of the global COVID-19 pandemic and related discontinuities. It asserts that emergency related teaching is justified by the urgent need to maintain continuity of teaching and learning and to avoid knowledge and skills decay. A systematic approach to evaluate the effectiveness of emergency remote teaching involves measuring variables across four dimensions;that is, context, input, process, and outcomes. Weighting these dimensions is necessary to ensure that context, input, and process are prioritised above outcomes because the essence of the teaching model, when implemented, is to get it in place swiftly in order for teaching and learning to continue. The effectiveness of emergency remote teaching is best assessed on the basis of its speedy set-up and implementation to maintain continuity of teaching, not on student outcomes. The chapter investigated the approach that a sample of colleges and universities have followed to evaluate their model of emergency remote teaching and contrast it with theory. The approach found in practice was not aligned to best practice. Based on the evidence, the chapter proposes an evaluation framework that institutions can adopt specifically for evaluating emergency remote teaching practice. © 2022 by Byron A. Brown.

Blockchain technology in teaching, learning, and academic administration as a long-term solution to emergencies in higher education

The application of blockchain, particularly through avenues in teaching and learning and academic administration, has created scope for a new business model in higher education. Although higher education institutions in many African countries including Botswana are yet to adopt blockchain in their institutional processes, the chapter points to seven unique areas of practice in which the technology could be infused. Distributed ledgers and smart contracts are among the blockchain functions that could assist in improving efficiency, security, and privacy in the way academic administration is executed especially in student identification, processing of student admission applications, degree certification, document authentication, and quality assurance. A distinct highpoint of the chapter is the attention it calls to student experience in the learning and teaching process, by highlighting that it stands to benefit from the collaborative learning model that blockchain enables. At a wider level, the conversation about blockchain-based pedagogy coalesces with the push by many African governments, in particular in Botswana, towards a digitally transformed society. Already, many colleges and universities have placed the focus on achieving 'smart campuses' as a strategic goal. Blockchain adoption is one such step towards a smart campus. The chapter theorises that higher education institutions cannot legitimately talk about smart campuses while still holding steadfast to manual systems and processes. © 2022 by Byron A. Brown.

Neoliberalism crisis and fundamental shifts in Africa's higher education provision in the 21st century

This chapter explores the circumstances in the global south that have been reshaping teaching and learning practices, with particular focus on the African context. Anchored on a literature review strategy, the chapter explores some of the key pressure points in the higher education context that have been the trigger of reforms in the core practice of teaching and learning in recent years. In particular, the chapter discusses the neoliberalism crisis associated with the coronavirus pandemic in higher education, drawing attention to the inequalities that it ignited: not all students were affected in the same way;not all universities or colleges were affected in the same way;and not all students had the learning technologies required to carry on their education in the same way. Alongside the COVID-19 concerns, the chapter reflects on other pressure points for change including developments in digital technologies and the internet and changing students and changing higher education markets in sub-Saharan Africa. It argues that these forces are among a wave of influences that higher education institutions across the African continent cannot ignore. They form a blend of neoliberal reforms that are pressurising academics to change pedagogical models and threatening certain core values of a university: academic freedom, autonomy, and truth. The chapter develops the argument that although multiple pressures-arising from the pervasive influences of technology and the COVID-19 pandemic-are mounting on the higher education sector to reform its pedagogical practices, it should not be at the expense of perpetuating injustices, particularly among students. © 2022 by Byron A. Brown.

The Translation of Protest: The Worldwide Readings Project of Andrei Kureichyk's Insulted. Belarus

On 9 August 2020, Belarus erupted in protest over the falsified election results promoted and endorsed by existing president Aliaksandar Lukashenka. Playwright, director, and member of the Coordination Council for the peaceful transfer of power in Belarus, Andrei Kureichyk was one of the thousands on the streets that month. In early September he finished a new play depicting the events leading up to and surrounding the largest anti-government demonstrations in Belarus's history. Before going into hiding, Kureichyk sent the play, Insulted. Belarus, to former Russian theatre critic John Freedman for translation. Together, the two men hoped to have a few theatres in various European and North American countries give a reading of the play in solidarity with the people of Belarus. Neither of them expected that, within two months, the play would be translated into eighteen languages and receive over seventy-seven readings on digital platforms. While many companies were eager to add their name to the global ledger of solidarity, the rise of authoritarianism, as well as the renewed reckoning with systemic racism and sexism in many cultures and countries around the world, additionally meant that many theatres found in the play a vehicle to reflect and comment on their own situations. This article, written by one of the initial participants of the project, attempts to chart how the Worldwide Readings of Insulted. Belarus navigated the translation of protest from Belarus to the world. Bryan Brown is Senior Lecturer at the University of Exeter and co-director of visual theatre company ARTEL (American Russian Theatre Ensemble Laboratory) and author of A History of the Theatre Laboratory (Routledge, 2019). He is a member of the editorial board of Theatre Dance and Performance Training, co-editing the special issue 'Training Places: Dartington College of Arts' (2018). © The Author(s), 2023.

Nursing a Radical Imagination: Moving from Theory and History to Action and Alternate Futures

Examining the historical context of healthcare whilst focusing on building a more just, equitable world, this book proposes a radical imagination for nursing and presents possibilities for speculative futures embracing queer, feminist, posthuman, and abolitionist frames. Bringing together radical and emancipatory perspectives from an international selection of authors, this book reflects on the realities created by the COVID-19 pandemic, recognizing that our situation is not new but the result of ongoing hegemonies and injustices. The authors attend to the history of nursing and related institutions, examining the assumptions, ideologies, and discourses that shape the discipline and its place within healthcare. They explore the impact of this context on contemporary nursing and look at alternative visions for the future. The final section specifically focuses on ways that we can move forward. Envisioning new possibilities for nursing, this innovative volume is a vital resource for practitioners, scholars and students keen to promote social justice within and without nursing. It is an important contribution to nursing theory, philosophy and history. © Jess Dillard-Wright, Jane Hopkins-Walsh, and Brandon Brown 2023 selection and editorial matter, individual chapters, the contributors.

Rates of Inpatient Hospitalization for Acute Pancreatitis in Patients <=21-Years-Old during the Covid-19 Pandemic

Background: Multiple studies to date in both pediatric and adult literature have suggested a possible link between acute pancreatitis and recent COVID-19 infection. There have also been several case reports in the pediatric population describing children who presented with acute pancreatitis found to be SARS-CoV-2 PCR positive. Objective(s): The primary aim of our study was to observe acute pancreatitis admission trends in patients <=21-years-old at a local children's hospital between March 1, 2016 and February 28, 2021. The secondary aim was to observe the relationship between COVID-19 and pancreatitis since the onset of the COVID-19 pandemic. We hypothesized that there is an increase in acute pancreatitis admissions in patients <=21 years since the onset of the COVID-19 pandemic, which may be best explained as a post-viral sequela of a recent COVID-19 infection. Method(s): This study is a retrospective chart review that consisted of the following inclusion criteria: any individuals hospitalized <=21 years of age at time of admission with the diagnosis of acute pancreatitis and a peak lipase >200 u/L. Additional data was also obtained including date of admission, duration of admission, peak lipase, etiology of acute pancreatitis, and SARS-CoV-2 IgG and PCR status. Result(s): Over the course of 5 years, 91 patients met the inclusion criteria across 116 admissions for acute pancreatitis. The average number of admissions per year was 23 with highest during year 5 with 39. Females were affected highest with a rate of 1.6:1. The most common etiology of the 116 admissions for acute pancreatitis was idiopathic which accounted for 50 admissions, followed by gallstone pancreatitis which accounted for 23 admissions. Of the 39 patients admitted during the first year of the pandemic, only one was SARS-CoV-2 positive and 2 were SARS-CoV-2 IgG positive;23 had PCR testing obtained and only 9 had IgG testing obtained. Conclusion(s): From the data obtained, there is a statistically significant increase in total admissions for acute pancreatitis during the first year of the pandemic (39 admissions). With a large number of confounding variables, it cannot be concluded this is the result of a current or recent COVID-19 infection. The largest confounding variables include lack of testing for SARS-CoV-2 PCR or IgG and multiple readmissions for acute pancreatitis during the first year of the pandemic compared to any of the previous years. Future investigations should be made to standardize COVID PCR and SARS-CoV2 IgG testing for all patients admitted with acute pancreatitis if further data collection is to be obtained.

Building provincial capacity for sustainable agricultural mechanisation in Nepal

This project was originally envisaged as an 18-month development-oriented project based in Provinces 1 and 2 of the Nepal Terai. It aimed to build solidarity and teamwork around the drive for agri-mechanisation in each of these two provincial governments. Unfortunately, the short time frame paired with intensive efforts to establish new relationships and then the onset of COVID-19 meant that there was limited scope to deeply develop these new relationships and fully build the envisaged roadmap process and plans. Regardless of this, the project has made some essential steps in improving provincial agri-mechanisation planning and implementation, including: (1) substantial capacity developed though placement of engineering experts within the Nepal Agricultural Research Council (NARC), the Ministries of Agriculture, Land Management and Cooperatives (MoLMAC), various cooperatives and agricultural knowledge centres;(2) new and deepened relationships with and between key stakeholders, and particularly between NARC and provincial government, as well as with and between various cooperatives;(3) development of the first quantification of the status of agri-mechanisation on the Nepal Terai - indicating that there is high potential for rapid mechanisation if some key constraints are addressed;(4) publication of the learnings for a review of mechanisation in India and Bangladesh, and what that means for Nepal's agri-mechanisation planning;(5) regional learnings and new collaborations with various stakeholders in Nepal and West Bengal;(6) a national symposium on agri-mechanisation on the Nepal Terai, with a large number of supported individuals attending and learning from the national Agrimechanisation Fair;(7) development of a "roadmap" process that can be used more widely with additional further development;and (8) technical guidance and relationship building to improve the scaling of government supported custom hire centres in Province 1.

HazeL: A Low-Cost Learning Platform for Aerosol Measurements

The switch to online instruction during the COVID-19 pandemic forced educators to adapt hands-on environmental engineering experiments to a remote curriculum previously conducted in a laboratory using expensive analytical instruments (> $2000 per device). Here, we describe how we developed a low-cost (<$200) aerosol sensor platform as a successful solution for supporting remote laboratories on air quality for environmental engineering courses in Spring 2021, and continued for in-person classes in Spring 2022. This sensor platform, called HazeL (Haze Laser Sensor), consists of an externally mounted aerosol sensor, a GPS receiver, and temperature and pressure sensors coupled to an Arduino MKR WiFi 1010 microcontroller connected via a Grove system. Using a project-based learning approach and implementing the scientific method, students worked asynchronously to design experiments, collect aerosol measurements, and analyze and visualize data using the R programming language. Students generated hypotheses regarding factors affecting air pollution, measured >= 0.3 mu m particles in different locations, tested differences between samples, and rejected the null hypothesis if appropriate. HazeL was also used for projects on data processing and statistical inference in an upper-level computational course. We present an instructional guide on manufacturing the HazeL platform and using it as a teaching tool for enhancing student experiential learning, participation, and engagement.

College students in China during initial COVID-19 pandemic: Role of social media on attitudes toward preventive measures.

Objective: To examine the direct and indirect associations (through risk perceptions) between college students' social media use and their perceived importance of COVID-19 preventive measures. Participants and Method: 1,353 undergraduate students in China completed an online survey in 2020 Spring. Results: Participants reported high reliance on social media for COVID-19 updates, which was positively associated with perceived importance of preventive measures. Information-oriented social media use was associated with higher perceived importance of preventive measures not only directly but also indirectly via increased cognitive and emotional risk perceptions. Social-oriented media use, on the other hand, had a negative direct association with perceived importance of preventive measure as well as a positive indirect association via emotional risk perception. Conclusions: This study shows that social media are important information sources for college students during the early stage of the pandemic and their response to the pandemic was related to social media use.

INTRODUCING AN EVIDENCE-BASED MINDFULNESS CURRICULUM IN A PEDIATRIC RESIDENCY PROGRAM - LESSONS FROM A PILOT STUDY

Purpose of Study Burnout is experienced by over 60% of physicians in the US with a 10% increase in the past year, and leads to degradation of patient care, low professional satisfaction, increased physician turnover, and increased healthcare costs. The COVID-19 pandemic has magnified and exacerbated these challenges. Pediatric mental impact from this healthcare crisis has been referred to as the second pandemic, and dealing with it requires health professionals to be centered and resilient. Physicians experiencing burnout can suffer from denial at first, preventing early intervention. One proposed solution is incorporating mindfulness-based meditation into the residency wellness curriculum. This study compared a pilot study in 2019 with a subsequent study in 2021 incorporating changes reflecting lessons learned from the pilot study, to measure burnout in pediatric residents before and after the implementation of a 3 month mindfulness-based meditation curriculum. Methods Used Comparison was made between a pilot study in mindfulness conducted in the department of pediatrics in 2019, and a Phase II in the departments of pediatrics and pastoral care in 2021. The outcome measures were: number of participants attending the sessions and the percentage compliance in filling the initial survey, final survey and post-meditation short surveys. The changes implemented included interdepartmental participation, increase in the number of 'mindfulness ambassadors', making attendance possible virtually (online) as well as physical presence, and making the surveys accessible online instead of paper-only (see table 2). Summary of Results There was a 20% increase in compliance filling the initial and final surveys between the pilot study and phase II (see figure 1). There was also a 30% increase in compliance with post-meditation surveys in 2021 as compared to the pilot study in 2019. It's noteworthy that phase II occurred during the first peak of the COVID pandemic, when residents were stretched thin. It was difficult ensuring consistent participation secondary to this, but phase II showed increased compliance in spite of these challenges. Conclusions Survey participation with consequent increase in the power of the study is critical in making survey-based research studies relevant. The integrity of such studies is often compromised by attenuation in the numbers of participants, as well as incomplete survey filling as a result of 'survey fatigue'. Valuable lessons were learned during the pilot study and when changes were implemented in the subsequent study, statistical power increased, proving higher relevance and effectiveness. (Table Presented).

Diurnal Variability of SARS-CoV-2 RNA Concentrations in Hourly Grab Samples of Wastewater Influent during Low COVID-19 Incidence

Wastewater-based epidemiology (WBE) has been widely deployed during the COVID-19 pandemic, but with limited evaluation of the utility of discrete sampling for large sewersheds and low COVID-19 incidence. In this study, SARS-CoV-2 RNA was measured in 72 consecutive hourly influent grab samples collected at a wastewater treatment plant serving nearly 500000 residents when incidence was low (approximately 20 cases per 100000). We characterized diurnal variability and relationships between SARS-CoV-2 RNA detection and physicochemical covariates [flow rate, total ammonia nitrogen (TAN), and total solids (TS)]. The highest detection rate observed was 82% during the first peak flow, which occurred in the early afternoon (14:00). Higher detection rates were also observed when sampling above median TAN concentrations (71%;p < 0.01;median = 40.26 mg of NH4/L). SARS-CoV-2 RNA concentrations were weakly correlated with flow rate (Kendall's τ = 0.16;p < 0.01), TAN (τ = 0.19;p < 0.05), and TS (τ = 0.18;p < 0.01), suggesting generally low RNA sewer discharges as expected at low incidence. Our results elucidated sensible adjustments to maximize detection rates, including using multiple gene targets, collecting duplicate samples, and sampling during higher flow and TAN discharges. Optimizing the lower-incidence bounds of WBE can help assess its suitability for verifying COVID-19 reemergence or eradication. ©

Alternative Workflow for SARS-CoV-2 Testing Using a Heat Lysis Protocol for Respiratory Specimens

Background. The SARS-CoV-2 pandemic has demonstrated the need for streamlined workflows in high-throughput testing. In extraction-based testing, limited extraction reagents and required proprietary instrumentation may pose a bottleneck for labs. As a solution, ChromaCode developed a Direct Extraction protocol for the HDPCR™ SARS-CoV-2 Assay, distributed in accordance with the guidance on Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency, Section IV.C., which allows for the processing of specimens without an extraction system. In lieu of an extraction system, the Direct Extraction protocol uses a thermal cycler to lyse and inactivate specimens which are directly added to the Polymerase Chain Reaction (PCR). Methods. The Limit of Detection (LoD), Clinical Performance, and effect of Interfering Substances was determined for the Direct Extraction protocol. The LoD was established on 6 PCR platforms with dilutions of inactivated SARS-CoV-2 virus spiked into residual, negative nasopharyngeal swab (NPS) matrix. Clinical performance was assessed with 48 positive and 50 negative frozen retrospective samples using the Direct Extraction protocol compared to an external Emergency Use Authorized (EUA) comparator assays (cobas® Liat® SARS-CoV-2 & Influenza A/B assay and the Hologic Panther Fusion® SARS-CoV-2 Assay respectively) on three PCR platforms. The Direct Extraction protocol was evaluated for performance in the presence of 13 potentially interfering substances that can be present in a respiratory specimen. Results. The LoD of the Direct Extraction protocol ranges from 1000 - 3000 genomic equivalents (GE)/mL. The clinical performance of the assay was 95.8% positive agreement (95% CI of 84.6% - 99.3%) and 100% negative agreement (95% CI of 90.9% - 100% or 91.1% - 100%) across all three PCR platforms tested. The viral target was detected at 3X LoD for all interferents tested. Conclusion. The Direct Extraction protocol of ChromaCode's SARS-CoV-2 Assay is a sensitive test that eliminates the need for sample extraction and performs very well against traditional extraction-based workflows. The inclusion of this protocol can reduce costs, reliance on extraction systems, and time associated with extraction-based protocols.

Plasma Discharge Ionization Emission Spectra of Analytes and SARS-CoV-2 for Label-Free Sensing Applications

Ionization spectra of substances are extensively used in their label free detection. Here we demonstrate the possibility of using plasma ionization to detect airborne and saliva SARS-COV-2 viruses through their emission spectra. It consists of an ionization chamber monitored by a fiber-optic UV-VIS spectrometer. The technique is completely label-free and can be programmed in real-time to detect different viral particles through their ionization emission spectra. Its average sensitivity for detecting deoxyribonucleic acid (DNA) bases in water is 20%/g in 1 mL of water. Its selectivity for DNA bases is through their relative emission peaks for adenine at 439.5 nm, cytosine at 440, thymine at 440.5, and guanine at 421.5 nm. The emission spectra of different electrode materials were also obtained to account for their contributions to the emission spectra of analytes. Gold electrodes were used owing to their resistance to corrosion and very low reaction with ionized species. The technique has the potential to be used in the point-of-care diagnostic and testing applications. IEEE

Suboptimal Humoral and Cellular Immune Response to SARS-CoV-2 RNA Vaccination in Myeloma Patients Is Associated with Anti-CD38 and BCMA-Targeted Treatment

Background: Multiple myeloma (MM) patients are immunocompromised due to defects in humoral/cellular immunity and immunosuppressive therapy. Reports indicate that the antibody (Ab) response in MM after 1 dose of SARS-CoV-2 RNA vaccine is attenuated. The impact of treatment on cellular immunity after vaccination remains unknown. Methods: We analyzed SARS-CoV-2 spike-binding (anti-S) IgG level in 320 MM patients receiving SARS-CoV-2 RNA vaccination. Blood and saliva were taken at multiple time points and compared with serology data of 69 age-matched vaccinated healthcare workers. We profiled SARS-CoV-2-specific T cell responses in a subset of 45 MM patients and 12 age-matched healthy controls by flow cytometry and ELIspot. All subjects were enrolled in studies approved by the Institutional Review Board at the Icahn School of Medicine at Mount Sinai. Results: The 320 patients (median age 68 year) received two-dose RNA vaccines (69.1% BNT162b2, 27.2% mRNA-1273). Median time to diagnosis was 60 months with a median of 2 prior treatment lines (range 0-16). We included 23 patients with smoldering MM. Patients received various treatments at vaccination with 148 (43.8%) on anti-CD38-containing treatment, 36 (11.3%) on BCMA-targeted therapy and 59 (18.4%) not on active treatment (incl. SMM patients). At the last available evaluation prior to vaccination, 131 (40.9%) exhibited a complete response. At data cutoff, a total of 260 patients (81.3%) had anti-S IgG measured >10 days after the second vaccine (median 51 days). Of these, 84.2% mounted measurable anti-S IgG levels (median 149 AU/mL). In the control group, Ab levels were significantly higher (median 300 AU/mL). Ab levels in the vaccinated MM patients with prior COVID-19 were 10-fold higher than those of patients without prior COVID-19 (p<0.001). Repeat Ab measurements up to 60 days after second vaccination confirm delayed and suboptimal IgG kinetics, particularly in patients receiving anti-MM treatment compared to controls (Figure 1). MM patients on active treatment had lower anti-S IgG levels (p=0.004) compared to patients not on therapy (median 70 vs 183 AU/mL). Notably, 41 patients (15.8%) failed to develop detectable anti-S IgG: 24/41 (58.5%) were on anti-CD38, 13/41 (31.7%) on anti-BCMA bispecific Ab therapy and 4/41 (9.8%) >3 months after CAR T. Univariate analysis showed an association of disease-related factors with absence of anti-S IgG: more previous lines of treatment (>3 lines, p=0.035;>5 lines, p=0.009), receiving active MM treatment (p=0.005), grade 3 lymphopenia (p=0.018), receiving anti-CD38 therapy (p=0.042) and receiving BCMA-targeted therapy (p<0.001). Multivariate analysis (corrected for age, vaccine type, lines of treatment, time since diagnosis, response status and lymphopenia) confirmed that anti-CD38 (p=0.005) and BCMA-targeted treatment (p<0.001) are associated with not developing detectable anti-S IgG. Clinical relevance is emphasized by 10 cases of COVID-19 after 1 (n=7) or 2 vaccine doses (n=3, all without anti-S IgG) with 1 patient passing due to respiratory failure. We studied SARS-CoV-2-specific T cell responses >2 weeks after the second vaccine in 18 MM patients with undetectable anti-S IgG (seronegative), 27 with detectable anti-S IgG (seropositive) and 12 healthy seropositive controls. We found that seropositive MM patients had CD4+CD154+ T cells producing IFNg, TNFa and IL-2 at similar levels as controls, whereas in the seronegative MM cohort CD4 T cell responses were significantly reduced (p<0.005). SARS-CoV-2-specific CD8 T cell responses were overall weaker and not different across cohorts. This data suggests that absence of detectable IgG is associated with suboptimal response of humoral and cellular immunity. Conclusion: MM patients mount a suboptimal IgG response after SARS-CoV-2 vaccination, with 15.8% of patients without detectable anti-S IgG. Ongoing analyses will highlight durability of serological protection against COVID-19. Additional data on T cell responses and immunophenotyping in the context of vaccination will be upda ed at the meeting. Implications are continuation of non-pharmacological interventions, e.g. masking/social distancing, for vulnerable patients. The findings underscore a need for serological monitoring of MM patients after vaccination and for trials assessing use of prophylactic strategies or studies exploring additional immunization strategies. [Formula presented] Disclosures: Wang: Sanofi Genzyme: Consultancy. Chari: Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees;Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding;Millenium/Takeda: Consultancy, Research Funding;Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;Pharmacyclics: Research Funding;GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees;Secura Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees;Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Research Funding;Janssen Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Shattuck Labs: Consultancy, Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda: Consultancy, Research Funding;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cordon-Cardo: Kantaro: Patents & Royalties. Krammer: Kantaro: Patents & Royalties;Merck: Consultancy;Pfizer: Consultancy;Avimex: Consultancy;Seqirus: Consultancy. Jagannath: Legend Biotech: Consultancy;Karyopharm Therapeutics: Consultancy;Janssen Pharmaceuticals: Consultancy;Bristol Myers Squibb: Consultancy;Sanofi: Consultancy;Takeda: Consultancy. Simon: Kantaro: Patents & Royalties. Parekh: Foundation Medicine Inc: Consultancy;Amgen: Research Funding;PFIZER: Research Funding;CELGENE: Research Funding;Karyopharm Inv: Research Funding.