SEROPOSITIVE MYASTHENIA GRAVIS AS THE CAUSE OF MULTIPLE FAILED EXTUBATIONS AND A PROLONGED ICU STAY FOR COVID-19 PNEUMONIA: A CASE REPORT AND BRIEF LITERATURE REVIEW

SESSION TITLE: Autoimmune Disorders: Both Primary and Secondary SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Neurologic sequelae of COVID infection appear to be common. The infection may present with neurologic symptoms, unmask neurologic disease, or worsen established disease. Myasthenia gravis (MG) is an autoimmune neuromuscular disease (NMD) that does not appear to be a usual COVID sequela. We present an elderly veteran with COVID pneumonia who struggled to wean from mechanical ventilation (MV) secondary to neuromuscular weakness. He was ultimately diagnosed with seropositive MG. CASE PRESENTATION: A 79 year old male with a history of prior COVID infection complicated by need for mechanical ventilation (MV) complained of progressive cough and shortness of breath. He was admitted for treatment of community-acquired pneumonia. On hospital day 8, he developed respiratory failure, was intubated, and was transferred to the intensive care unit (ICU). He was diagnosed with COVID a second time. After antibiotics and supportive treatment, he successfully completed a spontaneous breathing trial and was extubated. Within 24 hours, he developed hypercapnia, necessitating reintubation. Given his need for repeat intubations, we ordered myositis titers and MG autoantibodies. After a fourth failed extubation, a tracheostomy was placed. On hospital day 32, his acetylcholine receptor binding antibody returned positive at 30.0, suggesting seropositive MG. His MG composite score was 11 (for ptosis and ventilator dependence). For further work-up, a CT chest excluded thymoma;a focused neurological exam was limited by sedation, and inpatient electrodiagnostics were not feasible. He received 5 days of intravenous immune globulin (40 mg), a Prednisone taper, and Rivastigmine 60 mg thrice daily. His symptoms improved and he was transferred to the floor. DISCUSSION: It is well established that coronaviruses exhibit neurotropism. However, it is unclear whether the novel coronavirus SARS-CoV-2 unmasks underlying neurologic illness or creates de novo disease. Critical care physicians are often tasked with making an initial diagnosis of neuromuscular disease (NMD). NMD is a known cause of complicated extubations. When the diaphragm and accessory respiratory muscles fatigue, respiratory decompensation ensues as full MV support is removed. In many cases, underlying illness is unmasked during this process of extubation. In our case, it is unknown whether infectious insult led to molecular mimicry and development of autoantibodies or unmasked latent neuromuscular disease. If the infection did cause his disease, it would be one of the first cases of COVID-associated MG to be published. Our case is a reminder that NMD is a secondary cause of extubation failure and may suggest MG as a cause of MV weaning failure secondary to COVID. CONCLUSIONS: Critical care physicians should be aware of this potential neuromuscular complication of COVID infection as it may complicate MV weaning, increase vent days, and prolong ICU stays. Reference #1: Collantes MEV, Espiritu AI, Sy MCC, Anlacan VMM, Jamora RDG. Neurological manifestations in covid-19 infection: A systematic review and meta-analysis. Can J Neurol Sci. 2021 Jan;48(1):66-76. Doi: 10.1017/cjn.2020.146. Epub 2020 Jul 15. PMID: 32665054. Reference #2: Huber M, Rogozinski S, Puppe W, Framme C, Hoglinger G, Hufendiek K, Wegner F. Postinfectious onset of myasthenia gravis in a COVID-19 patient. Front Neurol. 2020 Oct 6;11:576153. Doi: 10.3389/fneur.2020.576153. eCollection 2020. PMID: 33123081. Reference #3: Muralidhar Reddy Y, B SK, Osman S, Murthy JMK. Temporal association between SARS-CoV-2 and new-onset myasthenia gravis: Is it causal or coincidental? BMJ Case Rep. 2021 Jul 21;14(7):e244146. Doi: 10.1136/bcr-2021-244146. PMID: 34290032. DISCLOSURES: No relevant relationships by Jeffrey Li No relevant relationships by Anupa Nadkarni No relevant relationships by Justin Owens No relevant relationships by Jennifer Perry no disclosure on file for Hayley Sp res;

Profound racial disparities in COVID-19 associated hospitalizations in rural Southwest Georgia

Background: The coronavirus disease 2019 (COVID-19) is responsible for one of the largest public health crises the United States has seen to date. This study explores the outcomes of African American and non-African American COVID-19-positive patients hospitalized in rural Southwest Georgia to identify differences in morbidity and mortality between the groups. Methods: We performed a retrospective cohort analysis among adults aged >= 18 years admitted with COVID-19 between March 2, 2020 and June 17, 2020 at Phoebe Putney Health System. Data on demographics, comorbidities, presenting symptoms, and hospital course were obtained. Patients were divided into two groups: African Americans and non-African Americans. We examined differences in patient characteristics between groups using chi-square tests for categorical variables, t test for parametric continuous variables, and Wilcoxon rank-sum tests for non-parametric continuous variables. Statistical Analysis Software (SAS) version 9.4 was used for statistical analysis. Results: Among 710 patients, median age was 63 years, 43.8% were males, and 83.3% were African Americans. African Americans had higher prevalence of obesity and hypertension, were more likely to present with fever, and present with longer duration of symptoms prior to presentation. In-hospital mortality was similar between the groups, as was need for mechanical ventilation, ICU care, and new dialysis. African Americans were more likely to be discharged home compared to non-African Americans. Conclusions: There was no difference in in-hospital mortality;however, African Americans had disproportionately higher hospitalizations, likely to significantly increase the morbidity burden in this population. Urgent measures are needed to address this profound racial disparity.

Children as innovators: harnessing the creative expertise of children to address practical and psychosocial challenges of the coronavirus disease 2019 (COVID-19) pandemic - COVISION study protocol

Background: We are currently in a period of transition, from the pre-COVID-19 (coronavirus disease 2019) era and the initial reactive lockdowns, to now the ongoing living with and potentially the after COVID-19 period. Each country is at its own individual stage of this transition, but many have gone through a period of feeling adrift;disconnected from normal lives, habits and routines, finding oneself betwixt and between stages, similar to that of liminality. Children and young people have been particularly affected. Aim: To increase the understanding of home and community-based strategies that contribute to children and young people's capacity to adjust to societal changes, both during and after pandemics. Moreover, to identify ways in which children's actions contribute to the capacity of others to adjust to the changes arising from the pandemic. The potential for these activities to influence and contribute to broader social mobilisation will be examined and promoted. Research design: To achieve the aim of this study, a participatory health research approach will be taken. The overarching theoretical framework of the COVISION study is that of liminality. The study design includes four work packages: two syntheses of literature (a rapid realist review and scoping review) to gain an overview of the emerging international context of evidence of psychosocial mitigations and community resilience in pandemics, and more specifically COVID-19;qualitative exploration of children and young people's perspective of COVID-19 via creative outlets and reflections;and participatory learning and action through co-production.

Using Technology to Improve Assessment Facilitation on a Policing Apprenticeship Programme: From COVID-19 Contingency to Best Practice

This article evaluates the introduction of an online assessment protocol to student officers on a Police Constable Degree Apprenticeship (PCDA) programme in the aftermath of the implementation of the COVID-19 global pandemic lockdown. This evaluation comes from conducting two cycles of action research to examine and improve the provision of an online multiple choice/short question exam which came about as a result of the lockdown, and the necessary withdrawal of university staff from face-to-face contact. The study shows that the introduction of the online exam was successful and contributed to a positive student experience, while providing vital feedback to the programme team to make continual improvements and can be progressed after lockdown and into the 'new normal'.

COVID-19 instruction style (in-person, virtual, hybrid), school start times, and sleep in a large nationwide sample of adolescents

Introduction: The COVID-19 pandemic significantly disrupted how and when adolescents attended school. This analysis used data from the Nationwide Education and Sleep in TEens During COVID (NESTED) study to examine the association of instructional format (in-person, virtual, hybrid), school start times, and sleep in a large diverse sample of adolescents from across the U.S. Methods: In October/November 2020, 5346 nationally representative students (grades 6-12, 49.8% female, 30.6% non-White) completed online surveys. For each weekday, participants identified if they attended school in person (IP), online-scheduled synchronous classes (O/S), online-no scheduled classes (asynchronous, O/A), or no school. Students reported school start times for IP or O/S days, and bedtimes (BT) and wake times (WT) for each applicable school type and weekends/no school days (WE). Sleep opportunity (SlpOpp, total sleep time proxy) was calculated from BT and WT. Night-tonight sleep variability was calculated with mean square successive differences. Results: Significant differences for teens' sleep across instructional formats were found for all three sleep variables. With scheduled instructional formats (IP and O/S), students reported earlier BT (IP=10:54pm, O/S=11:24pm, O/A=11:36pm, WE=12:30am), earlier WT (IP=6:18am, O/S=7:36am, O/A=8:48am, WE=9:36am), and shorter SlpOpp (IP=7.4h, O/S=8.2h, O/A=9.2h, WE=9.2h). Small differences in BT, but large differences in WT were found, based on school start times, with significantly later wake times associated with later start times. Students also reported later WT on O/S days vs. IP days, even with the same start times. Overall, more students reported obtaining sufficient SlpOpp (>8h) for O/S vs. IP format (IP=40.0%, O/S=58.8%);when school started at/after 8:30am, sufficient SlpOpp was even more common (IP=52.7%, O/S=72.7%). Greater night-tonight variability was found for WT and SlpOpp for students with hybrid schedules with >1 day IP and >1 day online vs virtual schedules (O/S and O/A only), with no differences in BT variability reported between groups. Conclusion: This large study of diverse adolescents from across the U.S. found scheduled school start times were associated with early wake times and shorter sleep opportunity, with greatest variability for hybrid instruction. Study results may be useful for educators and policy makers who are considering what education will look like post-pandemic.

Adolescent sleep variability, social jetlag, and mental health during COVID-19: Findings from a large nationwide study

Introduction: Adolescents are vulnerable to short, insufficient sleep stemming from a combined preference for late bedtimes and early school start times, and also circadian disruptions from frequent shifts in sleep schedules (i.e., social jetlag). These sleep disruptions are associated with poor mental health. The COVID-19 pandemic has impacted education nationwide, including changes in instructional formats and school schedules. With data from the Nationwide Education and Sleep in TEens During COVID (NESTED) study, we examined whether sleep variability and social jetlag (SJL) during the pandemic associate with mental health. Methods: Analyses included online survey data from 4767 students (grades 6-12, 46% female, 36% non-White, 87% high school). For each weekday, participants identified if they attended school in person (IP), online-scheduled synchronous classes (O/S), online-no scheduled classes (asynchronous, O/A), or no school. Students reported bedtimes (BT) and wake times (WT) for each instructional format and for weekends/ no school days. Sleep opportunity (SlpOpp) was calculated from BT and WT. Weekday night-to-night SlpOpp variability was calculated with mean square successive differences. SJL was calculated as the difference between the average sleep midpoint on free days (O/A, no school, weekends) versus scheduled days (IP, O/S). Participants also completed the PROMIS Pediatric Anxiety and Depressive Symptoms Short Form. Data were analyzed with hierarchical linear regressions controlling for average SlpOpp, gender, and school-level (middle vs high school). Results: Mean reported symptoms of anxiety (60.0 ±9.1;14%≧70) and depression (63.4 ±10.2;22%≧70) fell in the at-risk range. Shorter average SlpOpp (mean=8.3±1.2hrs) was correlated with higher anxiety (r=-.10) and depression (r=-.11;p's<.001) T-scores. Greater SlpOpp variability was associated with higher anxiety (B=.71 [95%CI=.41- 1.01, p<.001) and depression (B=.67 [.33-1.00], p<.001) T-scores. Greater SJL (mean=1.8±1.2hrs;94% showed a delay in midpoint) was associated with higher anxiety (B=.36 [.12-.60], p<.001) and depression (B=.77 [.50-1.03], p<.001) T-scores. Conclusion: In the context of system-wide education changes during COVID-19, students on average reported at-risk levels of anxiety and depression symptoms which were associated with greater variability in sleep opportunity across school days and greater social jetlag. Our findings suggest educators and policymakers should consider these sleep-mental health associations when developing instructional formats and school schedules during and post-pandemic.

Sleep disturbances, online instruction, and learning during COVID-19: Evidence from 4148 adolescents in the nested study

Introduction: COVID-19 fundamentally altered education in the United States. A variety of in-person, hybrid, and online instruction formats took hold in Fall 2020 as schools reopened. The Nationwide Education and School in TEens During COVID (NESTED) study assessed how these changes impacted sleep. Here we examined how instruction format was associated with sleep disruption and learning outcomes. Methods: Data from 4148 grade 6-12 students were included in the current analyses (61% non-male;34% non-white;13% middleschool). Each student's instructional format was categorized as: (i) in-person;(ii) hybrid [≥1 day/week in-person];(iii) online/synchronous (scheduled classes);(iv) online/asynchronous (unscheduled classes);(v) online-mixed;or (vi) no-school. Sleep disturbances (i.e., difficulty falling/staying asleep) were measured with validated PROMIS t-scores. A bootstrapped structural equation model examined how instructional format and sleep disturbances predict school/learning success (SLS), a latent variable loading onto 3 outcomes: (i) school engagement (ii) likert-rated school stress;and (iii) cognitive function (PROMIS t-scores). The model covaried for gender, race-ethnicity, and school-level Results: Our model fit well (RMSEA=.041). Examining total effects (direct + indirect), online and hybrid instruction were associated with lower SLS (b's:-.06 to -.26;p's<.01). The three online groups had the strongest effects (synchronous: b=-.15;95%CI: [-.20, -.11];asynchronous: b=-.17;[-.23, -.11];mixed: b=-.14;[-.19, -.098];p's<.001). Sleep disturbance was also negatively associated with SLS (b=-.02;[-.02, -.02], p<.001). Monte-carlo simulations confirmed sleep disturbance mediated online instruction's influence on SLS. The strongest effect was found for asynchronous instruction, with sleep disturbance mediating 24% of its effect (b = -.042;[-0.065, -.019];p<.001). This sleep-mediated influence of asynchronous instruction propagated down to each SLS measure (p's<.001), including a near 3-point difference on PROMIS cognitive scores (b = -2.86;[-3.73, -2.00]). Conclusion: These analyses from the NESTED study indicate that sleep disruption may be one mechanism through which online instruction impacted learning during the pandemic. Sleep disturbances were unexpectedly influential for unscheduled instruction (i.e., asynchronous). Future analyses will examine specific sleep parameters (e.g., timing) and whether sleep's influence differs in teens who selfreport learning/behavior problems (e.g., ADHD). These nationwide data further underscore the importance of considering sleep as educators and policy makers determine school schedules.

COVID stress and sleep disturbance among a racially/ethnically diverse sample of adolescents: Analysis from the nested study

Introduction: Using data from the Nationwide Education and Sleep in TEens During COVID (NESTED) study (N=6,578), we investigated if race/ethnicity (64.6% were White and 35.4% identified as a racial/ ethnic minority, mixed, or “other”) and community social vulnerability affected the association between COVID stress and sleep disturbance. Methods: Data on sociodemographic factors (age, race, sex, grade, zip code [for neighborhood social vulnerability index, SVI]), COVID-related stress, depression, anxiety, instructional format (online, in-person, or hybrid), and sleep disturbance (PROMIS Pediatric Sleep Disturbance) were captured through an online survey. Descriptive and inferential analyses (Hierarchical Binary Logistic Regression (HBLR), SPSS v. 25) in 4171 adolescents examined associations between sleep disturbance and COVID-related stress, adjusting for race, sex, SVI, grade level, learning format, household density, and mental health factors. Results: Sleep disturbance was prevalent among adolescents (89% above average, T-score >50);about two-thirds (64.4%) reported greater stress due to the pandemic. Compared to White (88.5%) adolescents, sleep disturbance was more common in Black (91.2%), Hispanic (90.5%), American Indian/Alaska native (95.1%), and Mixed (92.3%) and less common in Asian (83.9%) adolescents. Chi-square analysis indicated that both race/ethnicity (-2 = 14.96, p<.05) and SVI (-2 = 8.34, p<.05) had an effect on sleep disturbance. HBLR analysis indicated that compared to pre-pandemic, adolescents reporting “little stress” (OR=.70, 95% CI= .49-.99, p=.04) or “the ”same amount of stress' (OR=.64, 95% CI= .47-.89, p=.007) had lower odds of sleep disturbance. Higher depression (OR=1.06, 95% CI=1.04-1.07, p<.001) and anxiety (OR=1.05, 95% CI=1.04-1.07, p<.001) symptoms increased odds of sleep disturbance, while male gender lowered odds of sleep disturbance (OR=.11, 95% CI=.015-.86, p<.05). Overall, race/ethnicity (p=.44) and SVI (p=.45) did not independently predict sleep disturbance. Race/ethnicity stratified analyses indicated that for Black and Hispanic adolescents, being in grades 11/ 12 and depression predicted sleep disturbance;and for Asian adolescents SVI and anxiety predicted sleep disturbance. Conclusion: COVID-related stress and symptoms of depression and anxiety are associated with sleep disturbance. We observed differences in sleep disturbance across racial/ethnic groups and neighborhood social vulnerability strata, for specific racial/ethnic groups.

An automated approach to determine antibody endpoint titers for COVID-19 by an enzyme-linked immunosorbent assay.

While a variety of therapeutic options continue to emerge for COVID-19 treatment, convalescent plasma (CP) has been used as a possible treatment option early in the pandemic. One of the most significant challenges with CP therapy, however, both when defining its efficacy and implementing its approach clinically, is accurately and efficiently characterizing an otherwise heterogenous therapeutic treatment. Given current limitations, our goal is to leverage a SARS antibody testing platform with a newly developed automated endpoint titer analysis program to rapidly define SARS-CoV-2 antibody levels in CP donors and hospitalized patients. A newly developed antibody detection platform was used to perform a serial dilution enzyme-linked immunosorbent assay (ELISA) for immunoglobulin (Ig)G, IgM, and IgA SARS-CoV-2 antibodies. Data were then analyzed using commercially available software, GraphPad Prism, or a newly developed program developed in Python called TiterScape, to analyze endpoint titers. Endpoint titer calculations and analysis times were then compared between the two analysis approaches. Serial dilution analysis of SARS-CoV-2 antibody levels revealed a high level of heterogeneity between individuals. Commercial platform analysis required significant time for manual data input and extrapolated endpoint titer values when the last serial dilution was above the endpoint cutoff, occasionally producing erroneously high results. By contrast, TiterScape processed 1008 samples for endpoint titer results in roughly 14 minutes compared with the 8 hours required for the commercial software program analysis. Equally important, results generated by TiterScape and Prism were highly similar, with differences averaging 1.26 ± 0.2 percent (mean ± SD). The pandemic has created unprecedented challenges when seeking to accurately test large numbers of individuals for SARS-CoV-2 antibody levels with a rapid turnaround time. ELISA platforms capable of serial dilution analysis coupled with a highly flexible software interface may provide a useful tool when seeking to define endpoint titers in a high-throughput manner. Immunohematology 2021;37:33-43.While a variety of therapeutic options continue to emerge for COVID-19 treatment, convalescent plasma (CP) has been used as a possible treatment option early in the pandemic. One of the most significant challenges with CP therapy, however, both when defining its efficacy and implementing its approach clinically, is accurately and efficiently characterizing an otherwise heterogenous therapeutic treatment. Given current limitations, our goal is to leverage a SARS antibody testing platform with a newly developed automated endpoint titer analysis program to rapidly define SARS-CoV-2 antibody levels in CP donors and hospitalized patients. A newly developed antibody detection platform was used to perform a serial dilution enzyme-linked immunosorbent assay (ELISA) for immunoglobulin (Ig)G, IgM, and IgA SARS-CoV-2 antibodies. Data were then analyzed using commercially available software, GraphPad Prism, or a newly developed program developed in Python called TiterScape, to analyze endpoint titers. Endpoint titer calculations and analysis times were then compared between the two analysis approaches. Serial dilution analysis of SARS-CoV-2 antibody levels revealed a high level of heterogeneity between individuals. Commercial platform analysis required significant time for manual data input and extrapolated endpoint titer values when the last serial dilution was above the endpoint cutoff, occasionally producing erroneously high results. By contrast, TiterScape processed 1008 samples for endpoint titer results in roughly 14 minutes compared with the 8 hours required for the commercial software program analysis. Equally important, results generated by TiterScape and Prism were highly similar, with differences averaging 1.26 ± 0.2 percent (mean ± SD). The pandemic has created unprecedented challenges when seeking to accurately test large numbers of individuals for SARS-CoV-2 antibody levels with a rapid turnaround time. ELISA platforms capable of serial dilution analysis coupled with a highly flexible software interface may provide a useful tool when seeking to define endpoint titers in a high-throughput manner. Immunohematology 2021;37:33­43.

Serum pooling for rapid expansion of anti-SARS-CoV-2 antibody testing capacity.

OBJECTIVES: Examine possible pooling strategies designed to expand SARS-CoV-2 serological testing capacity. METHODS: Negative pools were assessed to determine optimal optical density (OD) cutoffs, followed by spiking weak or strong positive samples to assess initial assay performance. Samples were then randomly subjected to pool and individual testing approaches. RESULTS: Single positive specimens consistently converted pools of 5, 10, or 20 into positive outcomes. However, weaker IgG-positive samples failed to similarly convert pools of 50 to a positive result. In contrast, a stronger individual positive sample converted all pools tested into positive outcomes. Finally, examination of 150 samples configured into pools of 5, 10, 20 or 50 accurately predicted the presence of positive or negative specimens within each pool. CONCLUSIONS: These results suggest that pooling strategies may allow expansion of serological testing capacity. While limitations exist, such strategies may aid in large-scale epidemiological screening or identification of optimal convalescent plasma donors.