The Changing Impact of Vaccines in the Covid-19 Pandemic: A Modeling Study

Background: Much of the world's population had already been infected with COVID-19 by the time that the Omicron variant emerged at the end of 2021, but the scale of the Omicron wave was larger than any that had come before or since, and left a global imprinting of immunity which changed the COVID landscape. In this study, we explore the changing value of vaccines in a landscape of dynamic immunity and rapidly evolving variants of concern. Method(s): We use Covasim, an established agent-based model of COVID-19 enhanced with detailed intra-host dynamics. First, we simulate a vaccine trial over March 2020 - April 2022 within a population resembling that of South Africa, and estimate how both vaccine efficacy (reduction in the risk of severe disease for vaccinated vs unvaccinated individuals) and efficiency (number of doses needed to avert a death) change as the population experiences waves of wild-type, Beta, Delta, and Omicron infections. Next, we introduce six hypothetical variants starting from February 2022 and evaluate the impact of (a) the existing set of vaccines, and (b) vaccines specifically targeted to the new variants. Result(s): We estimate that within our simulated population, vaccine efficacy against severe disease decreased from 80% to 20% in the wake of the first wave of wild-type COVID-19, then increased back to ~70% over the latter half of 2020 as population immunity waned. This pattern repeated following each subsequent wave of infections, with vaccine efficacy falling to its lowest (10%) in the immediate wake of the Omicron wave in December 2021. The efficiency of vaccination decreases over time at an increasing rate: at peak efficiency, fewer than 100 doses would have been required to avert a single death, but by the end of January 2022, we estimate that nearly 4,000 doses would be required to avert a single death. We find that variant-chasing vaccines will only add value above pre-existing vaccines if we can shorten the window between variant introduction and vaccine deployment to under three weeks, an impossible time-frame without significant NPI use. Conclusion(s): Although the vaccines have proven to be remarkably effective, our work demonstrates that the population immunity acquired over the first two years of the pandemic significantly reduced the impact per dose of doses delivered after this time. Next-generation vaccines to fight future COVID variants and/or other respiratory diseases must be delivered rapidly at scale for vaccine strategies to be maximally effective.

Addressing the unmet social needs of gynecologic oncology patients as identified by a universal screening tool in a safety net hospital

Objectives: To identify the unmet, actionable social needs of gynecologic oncology patients using a self-administered social needs assessment tool and quantify the interventions subsequently provided to our patients. Method(s): This is a study of data collected in an ongoing performance improvement initiative in a gynecologic oncology clinic at a safety net hospital and was determined to be exempt from review by the institutional IRB. Eligible patients completed the social needs screening tool from October 2021 to March 2022. The following social needs domains were assessed: food insecurity, utility insecurity, housing insecurity, transportation insecurity, need for childcare, exposure to violence, lack of companionship, difficulty reading, or difficulty accessing medical care due to fear of losing job. Patients were asked if they desired to speak with a social worker and if any needs were urgent. Data from the screening tool was collected and supplemented by data from the EMR. Univariate descriptive statistics were used to report the patient demographic information, prevalence of social needs, and referral rates for social needs identified. Result(s): There were 475 patients seen in the gynecologic oncology clinic since October 2021. 286 (60%) patients completed the screening tool. 139 (49%) screened positive for at least 1 social need;of those 98 (70%) were Hispanic with a median age of 56 years. 27 (6%) patients were receiving treatment for a gynecologic malignancy, of whom 19 (70%) had at least 1 social need. 25 (92%) patients were insured through Medi-Cal. 12 (44%) patients were being treated for endometrial cancer, followed by ovarian (7, 26%) and cervical (4, 15%). The social needs identified in all patients and in patients actively receiving cancer treatment are summarized in Fig. 1. Patients reporting lack of companionship were referred to mental health or cancer support groups through the American Cancer Society or the Los Angeles County Department of Public Health. Those needing transportation or utility services were linked with services available through their insurance or LA County, ride share vouchers, low-income energy assistance programs, COVID rent/mortgage relief programs. Patients with food and housing insecurity were assisted in applying for public housing or food stamps;local food banks were provided. Patients were assisted with applying for disability insurance as needed. To date, all actively treated patients reporting lack of companionship, need for transportation, avoiding medical care for fear of losing their job, and utility insecurity were provided resources;80% received resources for food insecurity. Conclusion(s): Universal screening for social needs in gynecologic cancer patients identifies a high rate of unmet needs within a safety net hospital. Cancer care navigators can successfully provide these patients community-based resources tailored to their individual social needs. Our next steps will be to determine if and how these resources impact our patients' experiences and treatment outcomes.[Formula presented]Copyright © 2022 Elsevier Inc.

Precarity of Subsistence: Social Reproduction Among South African Nurses

The concept of precarity extends beyond insecure wage work into the conditions of social reproduction: supporting dependents can expose even securely employed, relatively well-paid workers to precarity. Qualitative data from public hospital nurses in Johannesburg reveal how responsibility for social reproduction can contribute to precarity among women in some contexts. This study maps nurses' household networks to obtain a conservative estimate of dependency. Excerpts from interviews demonstrate how responsibilities are converted into precarity through household networks across different marital statuses, household structures, and ages. HIGHLIGHTS Securely employed, professional women may have precarious lives. Familial dependency can induce precarity among black women employed in nursing in South Africa. South African nurses were distressed prior to the COVID-19 pandemic. Gendered value systems and norms contribute to precarious subsistence. Universal basic income could mitigate micro-level crises of social reproduction. © 2022 IAFFE.

Educators' experiences of pivoting online: unearthing key learnings and insights for engaging students online

The impact of the COVID-19 pandemic meant that online teaching in higher education became the default. Educators were, and often now continue to be, required to pivot to online teaching, necessitating them to adapt their teaching delivery, effectively engage students online, and apply existing skills to new and unfamiliar pedagogical contexts. This paper presents a small international case study, investigating the experiences of a diverse group of educators who wanted to learn about engaging students because their higher education institutions were pivoting to online teaching. Following the educators' involvement in professional learning about a particular online engagement framework, the educators used their learning in their planning and online teaching. Data extracted from a deductive coding exercise augmented by qualitative data gleaned from semi-structured interviews was used to explore how the educators enhanced the engagement strategies they implemented in their courses. The findings indicate the types of learning processes used by the educators and how they applied their learning to online teaching. The deductive analysis suggests that the strategies the participants revealed worked well in their online practice correspond with the strategies delineated in the framework.

SARS-CoV-2 Antibody Levels Associate with Neutrophil Activation

Background. COVID-19 disease severity and outcomes have been linked to high antibody titers and a dysregulated neutrophil immune response. Here we query associations and connections between the endogenous SARS-CoV-2 antibody response and neutrophil activation in COVID-19. Methods. Baseline serum or plasma samples from 57 patients hospitalized on oxygen with COVID-19 were used to perform;1) quantitative measurements of SARS-CoV-2 specific antibodies using a luciferase-based immunoprecipitation system assay, 2) quantitative measurements of neutrophil specific biomarkers using Luminex technology, and 3) neutrophil extracellular traps (NETs) as measured by myeloperoxidase-DNA (MPO-DNA) complexes by ELISA. Absolute neutrophil count (ANC) and immature granulocyte count (IGC) were measured from complete blood counts (CBC). Antibody levels were compared by disease severity using Wilcoxon rank-sum test and correlations were generated between antibody levels and neutrophil activation markers using Spearman's correlation (SC). Results. In a cohort of hospitalized patients, severe/critical COVID-19 was associated with higher levels of nucleocapsid-IgA (p=0.011) as well as spike-IgG (p= 0.0007) compared tomoderate disease,while spike-IgA and nucleocapsid-IgG showed similar associations, trending towards significance (Figure 1A). Levels of IgG-spike and IgG-nucleocapsid both had significant correlations with the ANC (SC 0.33, p = 0.029;SC 0.38 p = 0.012). All four antibody titers showed strong correlations with IGC, lactoferrin and lipocalin-2, evidence of emergency granulopoiesis. Further, S100A9, a component calprotectin correlated with spike-IgG and nucleocapsid-IgA levels (SC 0.29, p = 0.030, SC 0.29 p = 0.029). Lastly, we found circulating NETs correlated with spike IgA levels (SC 0.38 p = 0.006), and its correlations with IgG-spike and IgA-nucleocapsid additionally approached significance with NETs levels as well (Figure 1B). Antibody Levels Correlate with Disease Severity and Neutrophil Activation Markers Figure 1: A) Levels of anti-Spike and anti-Nucleocapsid IgA and IgG levels measured in the serum of 57 unvaccinated hospitalized COVID-19 patients. Moderate illness represents ordinal scale 5 requiring low flow oxygen, while severe/critical patients represent ordinal scale 6 and 7, requiring high flow oxygen, non-invasive or mechanical ventilation, respectively. P values are compared by a Wilcoxon ranked sum test. B) Heatmap showing Spearman correlations between levels of anti-Spike and anti-Nucleocapsid IgA and IgG and markers of neutrophil activation. P values for individual correlations are represented in parentheses. MPO (myeloperoxidase), ANC (absolute neutrophil count), S100A9 (S100 calcium binding protein A9). Conclusion. Higher anti-spike and anti-nucleocapsid IgG and IgA levels associate with more severe COVID-19 illness. Further, endogenous SARS-CoV-2 specific antibody levels associate with markers of emergency granulopoiesis and neutrophil activation. Inhibiting antibody mediated neutrophil activation may improve outcomes in COVID-19.

Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: interim analysis of the DAYBREAK open-label extension study

Introduction: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for the treatment of adults with either relapsing forms of multiple sclerosis (RMS) or moderately to severely active ulcerative colitis. Objective(s): To report the safety and efficacy of extended exposure to ozanimod from an ongoing open-label extension (OLE) trial. Method(s): Patients with RMS who completed a phase 1, 2, or 3 ozanimod trial were eligible to enrol in DAYBREAK (NCT02576717), where they received ozanimod 0.92 mg/d. The primary objective was to evaluate safety in the overall population;treatment-emergent adverse events (TEAE) were monitored. Efficacy was evaluated with annualised relapse rate (ARR), calculated via negative binomial regression and pooled for all parent-trial treatment groups. Number of new/ enlarging T2 and gadolinium-enhancing (GdE) magnetic resonance imaging (MRI) brain lesions were reported for patients who entered the OLE from an active-controlled phase 3 trial. Result(s): In total, 2639 patients completed the parent trials;this interim analysis (datacut 1 February 2022) included 2494 patients with mean (range) ozanimod exposure of 56.4 (0.03- 74.7) months (11732.2 patient-years) in the OLE. In the OLE, 2199 patients (88.2%) had any TEAE, 352 (14.1%) had a serious TEAE (SAE), and 89 (3.6%) discontinued due to a TEAE. Similar rates of TEAEs and SAEs occurred when assessed by parent trial treatment group. The most common TEAEs (based on preferred terms) were nasopharyngitis (20.6%), headache (16.9%), upper respiratory tract infection (11.9%), COVID- 19 infection (11.5%), and lymphopenia (10.5%), which were generally similar to parent trial observations (excluding COVID-19 infection). Adjusted ARR in the OLE was 0.099 (95% CI, 0.083-0.119). After 60 months of treatment, 68% of patients were relapse free in the OLE. Three- and 6-month confirmed disability progression was observed in 15.9% and 14.0% of patients in the OLE, respectively. Mean number of new/enlarging T2 lesions per scan at 60 months was similar, regardless of parent trial treatment group (range, 0.77-0.98), as was mean number of GdE lesions at month 60 (range, 0.057-0.065). Conclusion(s): The safety and tolerability profile of ozanimod in DAYBREAK was consistent with prior reports. Ozanimod treatment demonstrated sustained efficacy on clinical and MRI measures of disease activity and on disability progression.

Teleneurology as a tool to overcome disparities for access to multiple sclerosis care

Background: Utilization of teleneurology for MS care rapidly expanded during the COVID-19 pandemic to maintain healthcare access. Disparities in telehealth use have been described in other health conditions, but not in a MS population. Objectives/Aims: To evaluate longitudinal utilization of teleneurology across age, race, geographic factors, and insurance categories to identify potential disparities in utilization at a single academic MS center (Cleveland Clinic). Method(s): MS patients attending a specialty clinic in Cleveland, a medium-sized city, who completed >=2 visits at least 24 months apart from 1/2019 to 6/2021 were studied. Patients with fully inperson care were compared to patients with <50% or >50% teleneurology care. Categories of age, race, geographic factors, and insurance were compared using Kruskal-Wallis tests and pairwise Wilcoxon rank sum tests with Bonferroni correction for multiple comparisons. Result(s): 892 patients met the inclusion criteria and completed 3710 visits during the study timeframe: mean age 49.1+/-11.7 years, 73.7% female, 85.6% white, median disease duration 11.2 years [0.15;60.3], and relapsing-remitting 62.3%. 37% patients were fully in-person, 37.2% patients had <50% teleneurology care, and 25.8% patients had >50% teleneurology care. There were no significant differences for race (white, black, other), insurance type (Medicare, Medicaid, private, non/other), area deprivation index (ADI), and residence location (rural vs metropolitan) in the use of teleneurology. Use of teleneurology care varied based by age, with older patients utilizing more in-person care. In person care was 23.4% for ages 18-39, 38.5% for ages 40-60, and 47.8% for those greater than 60 (p<0.001). Patients residing in greater Cleveland had significantly more in-person care (55.3%) compared to residents residing in Ohio outside of the greater Cleveland area (34.7%) and outside of Ohio (10.1%) (p=0.031). Conclusion(s): There were no significant differences in teleneurology utilization across race, insurance, ADI or rural vs metropolitan residence, suggesting it is a broadly accessible tool to overcome disparities in access to MS care. Utilization of teleneurology care for older and local patients was lower, which may be due to decrease demand in these groups. Future studies should assess the optimal integration of teleneurology and in-person visits in MS management.

COVID-19 infections and vaccinations among patients receiving ozanimod in the daybreak open-label extension trial

Introduction: COVID-19 emerged in late 2019. It is unclear whether selective sphingosine 1-phosphate (S1P) receptor modulators affect clinical outcomes of COVID-19 in patients with relapsing multiple sclerosis (RMS), including those who received SARS-CoV-2 vaccination. Objective(s): To characterise COVID-19 outcomes and vaccine breakthrough infections during ozanimod use, an S1P1 and S1P5 modulator, for treatment of RMS in an ongoing open-label extension (OLE) study. Method(s): DAYBREAK (NCT02576717), an OLE study of ozanimod 0.92 mg/d, began 16Oct2015. Patients who completed a phase 1-3 ozanimod RMS trial were eligible;>90% are from Eastern Europe. In this post hoc analysis, COVID-19 events from 1Nov2019 to 28Jan2022 in DAYBREAK were identified by MedDRA 24.1 COVID-19 SMQ (narrow scope). Each patient's most recent infection and all postvaccination infections were characterised. Result(s): Of 2181 patients in DAYBREAK during the analysis period, 319 (14.6%) developed COVID-19 (274 confirmed, 45 suspected). COVID-19 was nonserious in 291 (91.2%). During COVID-19, ozanimod was continued in 220 (69.0%) patients, interrupted in 94 (29.5%), and permanently discontinued in 3 (0.9%);action was unknown in 2 (0.6%) patients. At data cutoff, 285 (89.3%) had recovered (including 195 who had continued ozanimod), 6 (1.9%) recovered with sequelae, 5 (1.6%) were recovering, 16 (5.0%) had not recovered, and 5 (1.6%) died;a sixth COVID-19-related death due to lung abscess occurred after recovery with sequelae from COVID-19 infection. Of 1984 patients in DAYBREAK on 11Dec2020, when COVID-19 vaccines emerged, 596 (30.0%) received >=1 vaccine dose (415 [69.6%] mRNA;99 [16.6%] replication-defective viral vector;65 [10.9%] inactivated SARS-CoV-2;26 [4.4%] other);504 (25.4%) were fully vaccinated. COVID-19 occurred in 39/596 (6.5%) vaccinated patients and 213/1388 (15.3%) unvaccinated patients;3 postvaccination cases (including 1 case after 2 mRNA doses) were serious. Of 39 patients with postvaccination infections, 28 (71.8%) recovered (including 2/3 serious cases), 1 (2.6%) recovered with sequelae, 3 (7.7%) were recovering, and 7 (17.9%, including the third serious case) had not recovered at data cutoff. There were no COVID-19-related deaths among vaccinated patients. Conclusion(s): COVID-19 cases were largely nonserious, and the majority of infected patients recovered while continuing ozanimod. Few vaccinated patients developed COVID-19;most who did recovered without sequelae.

Covid-19 associated free hanging clots in acute symptomatic carotid stenosis.

BACKGROUND: Thrombotic complications including stroke were previously described following Covid-19. We aim to describe the clinical and radiological characteristics of Covid-19 related with acutely symptomatic carotid stenosis (aSCS). METHOD: All patients presenting with an aSCS were prospectively enrolled in an ongoing institutional database. Inclusion criteria for the Covid-19-aSCS group were a combination of both antigen test and a positive reverse-transcriptase (PCR) test for Covid-19 upon admission. Patients with additional potential etiologies for stroke including cardioembolism, carotid dissection or patients with stenosis of <50% on CTA were excluded. A cohort of non-Covid-19 related aSCS patients admitted to the same institution before the pandemic during 2019 served as controls. RESULTS: Compared to controls (n = 31), Covid-19-aSCS (n = 8), were younger (64.2 ± 10.7 vs 73.5 ± 10, p = 0.027), and less frequently had hypertension (50% vs 90%, p = 0.008) or hyperlipidemia (38% vs 77%, p = 0.029) before admission. Covid-19-aSCS patients had a higher admission NIHSS score (mean 9 ± 7 vs 3 ± 4, p = 0.004) and tended to present more often with stroke (88% vs 55%, p = 0.09) rather than a TIA. Covid-19-aSCS patients had higher rates of free-floating thrombus and clot burden on CTA (88% vs 6.5%, p = 0.002). Covid-19 patients also less often achieved excellent outcomes, with lower percentage of mRS score of 0 after 90-days (13% vs 58%, p = 0.022). CONCLUSION: Covid-19- aSCS may occur in a younger and healthier subpopulation. Covid-19- aSCS patients may have higher tendencies for developing complex clots and less often achieve excellent outcomes.

Statistical and agent-based modelling of the transmissibility of different SARS-CoV-2 variants in England and impact of different interventions.

The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and the agent-based model Covasim, in June 2021, to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B.1.177 and Delta to be 65-90% more transmissible than Alpha. Using these estimates in Covasim (calibrated 1 September 2020 to 20 June 2021), in June 2021, we found that due to the high transmissibility of Delta, resurgence in infections driven by the Delta variant would not be prevented, but would be strongly reduced by delaying the relaxation of restrictions by one month and with continued vaccination. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

Vaccination Recommendations for Psoriasis and Atopic Dermatitis Patients on Biologic Therapy: A Practical Guide

Novel biologic therapies have revolutionized the treatment of psoriasis and atopic dermatitis. Although they are generally safe, they are immunomodulatory and therefore unique considerations apply in regards to infections and vaccine administration. This review aims to provide a clear and practical guide for dermatologists or other healthcare providers to reference when caring for psoriasis or atopic dermatitis patients being treated with biologic therapies using currently available guidelines and clinical data. Vaccinations for approved biologics including TNF alpha, IL-12/23, IL-23, IL-17, and IL-4/13 inhibitors will be discussed, with a special note on current COVID-19 vaccination recommendations.

THE PROGNOSTIC IMPLICATIONS OF LIVER FUNCTION TEST ABNORMALITIES IN PATIENTS ADMITTED TO HOSPITAL WITH COVID-19

Background & Aims: Prior studies have indicated the presence of hepatic inflammation (as signified by elevated liver function test (LFT) values), as conferring an escalated risk toward adverse outcomes in patients admitted with COVID-19. In line with this hypothesis, we study the various thresholds of LFTs and its associated prognostic risks toward COVID- 19 related hospital deaths Method: This was a single-center retrospective study involving patients admitted with COVID-19. Univariate Cox regression analysis identified the LFT variables significantly associated with our primary endpoint, in-hospital death. Subsequently, 500 iterations of thresholds were generated for each biomarker to estimate the prognostic relationship between biomarker and endpoint. Multivariate Cox regression and event-analyses were performed for each threshold to identify the minimal cutoffs at which the prognostic relationship was significant. Event curves were drawn for each significant relationship. Results: A total of 858 patients with COVID-19 were included with a median follow-up time of 5 days from admission. From the total, 90 patients passed away during admission (10.5%). The deceased cases were more likely to be older (66.2 vs 55.3y p<0.001);however, there was no difference in gender (male: 66 vs 56.2% p=0.11). Between the cases and controls (no-death), deceased cases had higher incidence of nonalcoholic fatty liver disease (7.78 vs 2.99% p=0.042), COPD (18.9 vs 7.80% p=0.001), lung cancer (4.44 vs 0.65% p= 0.009), ICU admissions (81.1 vs 26% p<0.001), and intubation events (84.4 vs 19.5% p<0.001), however there was no difference in alcohol use (21.1 vs 30.6% p=0.083) and alcoholic liver disease (5.56 vs 2.08% p=0.097). Upon univariate Cox analysis, the following LFT parameters were associated with in-hospital death: Bilirubin (p<0.001), AST (p<0.001), ALT (p<0.001). However, alkaline phosphatase (p=0.449) was not associated with the primary endpoint. The iterations of event regression analyses using 500 sequences of LFT thresholds showed the following cutoffs to be significantly associated with in-hospital death (minimally significant values): ALT (281.71 IU/L), AST (120.94 IU/L), bilirubin (2.615 mg/ dL). On the multivariate analysis, while controlling for demographics and cardiopulmonary/ medical comorbidities, the following adjusted hazard ratios were derived for each cutoff: ALT (aHR: 6.43 95%CI 1.85-22.40), AST (aHR: 3.35 95%CI 1.84-6.11), and bilirubin (aHR: 2.77 95%CI 1.15-6.65). Conclusion: The delineated cutoffs for AST, ALT, and bilirubin levels can serve as clinical benchmarks to help determine when a COVID-19 infection poses significant risk. Given this finding, the cutoffs can be used as part of a risk assessment for patients to support early preventative therapies and medical management. (Table Presented)

A NOVEL PROGNOSTIC MODEL INCLUDING LIVER FUNCTION PARAMETERS ACCURATELY PREDICTS 30-DAY MORTALITY IN PATIENTS ADMITTED WITH COVID-19

Background and Aims: While the relationship between elevated liver enzymes and COVID- 19 related adverse events is well-established, a liver-dependent prognostic model that predicts the risk of death is helpful to accurately stratify admitted patients. In this study, we use a bootstrapping-enhanced method of regression modeling to predict COVID-19 related deaths in admitted patients. Method: This was a single-center, retrospective study. Univariate and multivariate Cox regression analyses were performed using 30-day mortality as the primary endpoint to establish associated hepatic risk factors. Regression-based prediction models were constructed using a series of modeling iterations with an escalating number of categorical terms. Model performance was evaluated using receiver operating characteristic (ROC) curves. Model accuracy was internally validated using bootstrapping-enhanced iterations. Results: 858 patients admitted to hospital with COVID-19 were included. 78 were deceased by 30 days (9.09%). Cox regression (greater than 20 variables) showed the following core variables to be significant: INR (aHR 1.26 95%CI 1.06-1.49), AST (aHR 1.00 95%CI 1.00- 1.00), age (aHR 1.05 95%CI 1.02-1.08), WBC (aHR 1.07 95%CI 1.03-1.11), lung cancer (aHR 3.38 95%CI 1.15-9.90), COPD (aHR 2.26 95%CI 1.21-4.22). Using these core variables and additional categorical terms, the following model iterations were constructed with their respective AUC;model 1 (core only): 0.82 95%CI 0.776-0.82, model 2 (core + demographics): 0.828 95%CI 0.785-0.828, model 3 (prior terms + additional biomarkers): 0.842 95%CI 0.799-0.842, model 4 (prior terms + comorbidities): 0.851 95%CI 0.809-0.851, model 5 (prior terms + life-sustaining therapies): 0.933 95%CI 0.91-0.933, model 6 (prior terms + COVID-19 medications): 0.934 95%CI 0.91-0.934. Model 1 demonstrated the following parameters at 0.91 TPR: 0.54 specificity, 0.17 PPV, 0.98 NPV. Bootstrapped iterations showed the following AUC for the respective models: model 1: 0.82 95%CI 0.765-0.882, model 2 0.828 95%CI 0.764-0.885, model 3 0.842 95%CI 0.779-0.883, model 4: 0.851 95%CI 0.808-0.914, model 5: 0.933 95%CI 0.901-0.957, model 6: 0.934 95%CI 0.901- 0.961. Conclusion: Model 1 displays high prediction performance (AUC >0.8) in both regression-based and bootstrapping-enhanced modeling iterations. Therefore, this model can be adopted for clinical use as a calculator to evaluate the risk of 30-day mortality in patients admitted with COVID-19. (Table Presented)

A Feasibility Cluster Randomised Controlled Trial of Paramedic- Administered Breathlessness Management Intervention for Acute- On-Chronic Breathlessness (BREATHE): Study Findings

Background/aims: One-fifth of conveyances to the emergency department (ED) are due to acute-on-chronic breathlessness. Paramedic breathlessness management may ease distress quicker and/or reduce ED conveyances. We evaluated the feasibility of a full trial of a paramedic delivered intervention to reduce avoidable conveyances (recruitment, randomisation, consent, training and intervention acceptability, adherence, data quality, best primary outcome, sample size estimation). The intervention comprised evidence-based non-drug techniques and a self-management booklet. Methods: This mixed-methods feasibility cluster randomised controlled trial (ISRCTN80330546) with embedded qualitative study about trial processes, training and intervention delivery, randomised paramedics to usual care or to intervention + usual care. Retrospective patient consent to use call-out data and prospective patient/carer consent for follow-up was sought. Potential primary outcomes were breathlessness intensity (numerical rating scale) and ED conveyance. Follow-up included an interview for patients/carers and questionnaires at 14 days, 1 and 6 months and paramedic focus groups and survey. Results: Recruitment was during the COVID-19 pandemic, leading to high demands on paramedics and fewer call-outs by eligible patients. We enrolled 29 paramedics;9 withdrew. Randomisation and trial procedures were acceptable. Paramedics recruited 13 patients;8 were followed up. Data quality was good. The intervention did not extend call-out time, was delivered with fidelity and no contamination and was acceptable to patients, carers and paramedics. There were no repeat call-outs < 48 hours. Recruitment stop-go criteria were not met. We had insufficient data for sample size estimation. Conclusions: A full trial in the same circumstances is not feasible. However, valuable information was gained on recruitment, attrition, consent, training and intervention acceptability and adherence, and patient-reported data collection.