EBUS audit: assessing the diagnostic performance of the service at UHL

Introduction: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an important diagnostic procedure in the lung cancer pathway. False-negative or inadequate sampling can lead to inaccurate staging or delay in diagnosis. This study was conducted to assess the performance of the Cancer EBUS service at a tertiary hospital. Method(s): We conducted a retrospective analysis of patients who underwent EBUS-TBNA for suspected cancer between 1st June 2021 to 31st May 2022. Request forms, CT reports, EBUS reports and pathology reports were reviewed for analysis. Result(s): 205 EBUS-TBNA procedures were performed. All patients had an appropriate staging CT prior to procedure. The mean time to test was 10.5 days (7.4). 77 (38%) had tests within 7 days of request. 293 lymph nodes and 10 mass lesions were sampled. The mean time to pathological results being received was 2.9 days (1.8). Final histology showed 39 (19%) cases of lung adenocarcinomas, 3 (1%) lung non-small cell carcinomas, 25 (12%) lung squamous cell carcinomas, 25 (12%) small cell cancers, 4 (2%) lung NOS, 3 (1%) pulmonary carcinoid, 2 (1%) lymphoma, 12 (6%) other cancers, 12 granulomata and 1 thyroid tissue (6%). 43 (21%) cases showed lymphoid tissue and 28 (14%) were reported as inadequate. No samples were taken in 8 cases (4%). Adequate tissue for predictive marker testing was available in 93% (66) of cases of non-small cell lung cancer (NSCLC). Complications were encountered in 9 cases (4%). Only 3 cases (1.5%) required any form of intervention. [Figure presented] Conclusion(s): Our data provides assurance of safety while also highlighting specific areas for attention regarding performance and time to test that can be addressed and our sensitivity was comparable to national standards. The increased waiting times may be partly related to COVID-19 precautions and will require reauditing at a later date. Disclosure: No significant relationships.Copyright © 2023 Elsevier B.V.

Every breath you take, we'll be watching you!

Background: Children and young people (CYP) receiving long term ventilation (LTV) need regular cardiorespiratory sleep studies (CRSS) for management. COVID-19 pandemic restrictions necessitated increased at-home monitoring. Home ventilators have downloadable data which could provide useful insight into ventilation adequacy. We share our preliminary experience with use of downloaded ventilator data to manage LTV patients. Aim(s): Ventilator data from CYP receiving LTV was analysed. We hypothesised that detailed analysis of this data could assist clinical decision making. Method(s): 2-year ventilator download data (ResScan software, ResMed Sleep Solutions, UK) was retrospectively reviewed. Parameters included oxygen saturations, ventilator usage, pressure, air flow and leak. Respiratory rate and tidal volume helped calculate minute ventilation. "Breath-by breath' data was analysed by sleep physiologist and detailed report was provided for clinician review. Result(s): 95 ventilator downloads (36 BIPAP/ 59 CPAP) were analysed in 81 CYP. Poor ventilator adherence was identified in 11/95 (12%). Interface / mask issues were identified in 12/95 (13%). Further CRSS was required in only 4 cases (3%) and clinical interpretation was possible in the remainder. As a result, ventilation parameters were weaned in 17, increased in 5 and unchanged in rest. Conclusion(s): Detailed analysis of ventilator data was sufficient to permit clinical decision making in majority of CYP receiving LTV during the pandemic. It provides valuable information about adherence, interface issues and ventilation for management of these patients. Further validation of this methodology against existing CRSS techniques and to evaluate its role as a stand-alone investigation would be required.

Safety and tolerability of inhaled molgramostim in autoimmune pulmonary alveolar proteinosis (aPAP)

Background: aPAP is a rare lung disease characterized by surfactant build-up for which there is no approved pharmacologic treatment. aPAP patients typically present with shortness of breath due to impaired oxygen transfer in the lung . Objective(s): To report the long-term safety of inhaled molgramostim nebulizer solution (MOL) administered intermittently in aPAP patients: open-label IMPALA-X extension study (NCT03482752). Method(s): Patients who completed IMPALA (NCT02702180) were eligible for IMPALA-X. MOL (300 mug;once daily) was administered in cycles of 7 days on/7 days off treatment. The primary endpoint included adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), and discontinuations. Result(s): Safety data from 59 patients were analyzed;44 (74.6%) and 15 (25.4%) patients had >=12 and >=24 months of exposure, respectively. Forty (67.8%) patients reported 165 AEs;138 AEs in 38 (64.4%) patients were treatmentemergent AEs (TEAEs). Eight patients had SAEs that were considered unlikely related to treatment. Seven patients had severe TEAEs and 3 were considered treatment-related/ADRs. Most common AEs (7 patients each, 11.9%) were cough and nasopharyngitis. Respiratory tract infection, arthralgia, alveolar proteinosis, and COVID-19 were each reported by 6.8% patients. No TEAEs led to treatment discontinuation/withdrawal. One subject died following COVID-19 infection 24 days after the last MOL dose. Conclusion(s): IMPALA-X was discontinued early as intermittent dosing did not show a benefit vs placebo in the IMPALA study. The phase 3 IMPALA-2 study of continuous daily MOL vs placebo in patients with aPAP is ongoing.

S6 Timing of pneumothorax post-CT-guided thoracic biopsy in a tertiary referral centre: implications for the ambulatory pneumothorax pathway

S6 Table 1Study population characteristicsn % Total number of procedures 641 - Male 371 57.9% Female 270 42.1% Median age (years) 71.0 - Lesion site RUL 177 27.61% RML 22 3.43% RLL 109 17.00% LUL 151 23.56% LLL 104 16.22% Anterior mediastinal 29 4.52% Pleural 40 6.24% Chest wall 9 1.40% Median lesion size (mm) 41 - Total pneumothorax incidence 223 34.8% Timing of pneumothorax T = 0 hours 186 83.41% T = 0-2 hours 37 16.59% T = 2 hours - 7 days 0 0.00% Pneumothorax management(% of n=223) Conservative 144 64.57% Aspiration 47 21.08% Chest drain 31 13.90% Pleural vent 1 0.45% Total pneumothorax needing intervention (% of n=223) 79 35.43% Immediate pneumothorax management (% of n=186) Conservative 111 59.68% Aspiration 46 24.73% Chest drain 28 15.05% Pleural vent 1 0.54% Immediate pneumothorax needing intervention (% of n=186) 75 33.63% Delayed pneumothorax management (% of n=37) Conservative 33 89.19% Aspiration 1 2.70% Chest drain 3 8.11% Pleural vent 0 0.00% Delayed pneumothorax needing intervention (% of n=37) 4 10.81% ConclusionsThis study demonstrates that the incidence of delayed-onset pneumothorax requiring intervention is low in a tertiary centre setting. The optimal time for patient observation post-CTGB remains unknown. The authors acknowledge a high incidence of pneumothorax in the study cohort, which they postulate may be due to a higher volume of complex procedures in a tertiary setting, higher sensitivity of CT for reporting trivial post-biopsy pneumothorax, and the diversion of more complex lung cancer patients to the CTGB route during the COVID pandemic to avoid aerosol-generating procedures.ReferenceHeerink WJ, de Bock GH, de Jonge GJ, Groen HJ, Vliegenthart R, Oudkerk M. Complication rates of CT-guided transthoracic lung biopsy: meta-analysis. Eur Radiol 2017;Jan;27(1):138–148.

Infection with Covid Variants of Concern in a Lung Transplant Population

The COVID pandemic has evolved as the SARS-2 Coronavirus (CoV-2) mutated into unique variants of concern (VOC). The clinical approach to COVID has evolved as new therapeutics have become available. Previous reports demonstrate differences in patient outcomes based on VOC, however outcomes in a lung transplant population have not been described. Our lung transplant program follows over 300 transplant recipients. Relevant information including date of first positive test, hospital admission, monoclonal antibody (mAb) or oral anti-viral treatment, CoV-2 vaccination history, tixagevimab/cilgavimab (T/C) and COVID attributed mortality have been tracked for quality improvement purposes. Outcomes were stratified by predominant US VOC at time of positive testing: wild strain 02/2020-02/2021, alpha strain 02/2021-05/2021, delta strain 06/2021-12/2021, omicron strain 01/2022- 09/25/2022. From 03/20/2020 through 09/25/2022, 142 recipients were diagnosed with COVID 152 times, including 9 recipients infected twice and 1 recipient infected 3 times. Most infected recipients tested positive with CoV-2 during the omicron wave. All recurrent infections occurred during the omicron wave. 8 deaths (5.6%) were attributed to COVID: 6 due to COVID respiratory failure, 1 stroke and 1 new restrictive-chronic lung allograft dysfunction. Therapies directed against CoV-2 were more likely administered in delta and omicron waves. Recipients were more likely to require hospital admission in wild type and alpha waves of CoV-2. Most deaths occurred in the wild type and delta waves. Deceased recipients, and those requiring hospital admission received less vaccinations and were less likely to have received T/C. (Table) This analysis shows changing trends in management and outcomes over the COVID pandemic. Future research should focus on transplant specific outcomes, including post-infection changes in allograft function and risk of developing chronic lung allograft dysfunction based on likely infecting VOC. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An Observational Study on the Humoral and Cellular Immune Response to SARS-CoV-2 mRNA Vaccination in Multiple Sclerosis and Other Autoimmune Neurological Disorders Treated With Anti-CD20 Therapies

Objective To assess adaptive immunity to SARS-CoV-2 in anti-CD20 treated individuals with mRNA vaccination. Background Anti-CD20 therapies attenuate humoral responses to vaccines. However, their effect on T cell responses is less clear. We examined B and T cell responses following COVID-19 vaccination in patients receiving anti-CD20 therapy for multiple sclerosis (MS) and other autoimmune inflammatory neurologic diseases (AINDs, e.g., autoimmune encephalitis, stiff person syndrome, etc.). Design/Methods MS and AIND patients on anti-CD20 therapies were prospectively enrolled for longitudinal analysis of antibody and T cell responses after a 3rd COVID-19 vaccination. Serum antibodies against the receptorbinding domain of the S1 spike protein (RBD-S1 IgG), neutralizing antibodies, and SARS-CoV-2 CD8 T cell responses, using activationinduced markers (AIM) and INF-gamma release assays (EUROIMMUN, Germany), were measured at various time points including prevaccination, post initial vaccination series, and 4 and 12 weeks after 3rd dose. Results Thirty-four MS and AIND participants are enrolled. Results for these patients (mean age 52 years-old, 79% female, 21 Pfizer, 13 Moderna) demonstrated attenuated RBD IgG antibody responses. However, a robust CD8 T cell response was observed, following a two-dose series, compared to non-immunosuppressed, age-matched vaccinated controls or unvaccinated with severe SARS-CoV-2 infection (p = 0.01). T cell response was sustained long-term (>12 weeks post 3rd dose) in all 11 anti-CD20 patients analyzed thus far. Collections are completed for all participants at 12 weeks and analysis to be completed by 05/15/22. Further analysis includes correlation of the INF- gamma release assay compared to RBD-CD8 T cell response detected by AIM assay. Conclusions Results suggest that patients treated with anti-CD20 therapy generate a robust CD8 T cell response to SARS-CoV-2 mRNA after three doses but remain with attenuated humoral immune responses. Our observational study will provide important data to guide vaccine management in patients on or anticipating anti-CD20 therapy.

Evaluation of nasal swab collection methods on a university campus during the SARS-CoV-2 pandemic

Background. Characterizing SARS-CoV-2 outbreaks on university campuses is critical for informed public health measures and understanding transmission dynamics. Figure 1. Dropbox and Kiosk Samples Collected September 10, 2021 to April 23, 2022. Methods. Faculty, staff, and students at a major public university in Seattle, WA, USA were enrolled in a COVID-19 testing study. Individuals could test using observed self-swabs at on-campus kiosks or unobserved self-swabs using a kit and returning it to a dropbox on campus. Sample collection volume for observed self-swabs was limited by staffing and space. All samples were returned to the laboratory and tested for SARS-CoV-2 by qRT-PCR. Results. From September 10, 2021 to April 23, 2022, 38,400 individuals were enrolled in the study. Of these individuals, 5,089 used dropboxes only, 14,421 used kiosks only, and 5,820 used both. A total of 21,653 dropbox swabs and 75,493 observed self-swabs were collected. Median age was similar between individuals using dropboxes and observed self-swabs (20 vs. 22 years). A greater proportion of dropbox users were students compared to faculty and staff (students made up 83% of dropbox only population, 75% of kiosk only, and 86% of both, chi2 p-value< 0.0001). Symptom data was reported for 65,349 swabs. Dropbox users were less likely to have symptoms compared to observed self-swab users (24% of swabs vs. 54%, chi2 p-value< 0.0001). SARS-CoV-2 positivity was slightly lower for dropboxes compared to kiosks (4% vs. 5%;p=0.001). Dropboxes were highly utilized during periods of increased testing demand, including after academic breaks and variant emergence (Figure 1). Of the total tests distributed for use, a greater proportion of dropbox kits were unable to be resulted (6%) compared to observed self-swab kits (0.02%). Conclusion. Dropboxes provided a flexible, high-volume collection method at times of increased testing demand. Individuals who used dropboxes were less likely to report symptoms and slightly less likely to test positive, suggesting a role for dropbox utilization in high-risk asymptomatic individuals during periods of high community transmission on a university campus.

Predictive Value of Procalcitonin across Disease States within an Inpatient Veteran Population

Background. Procalcitonin (PCT) can be elevated with certain bacterial infections. Debate continues as to how to best use this biomarker to guide antibiotic use. The primary objective of this study was to evaluate the correlation of PCT levels and the presence of bacterial infection on admission in the total population and in different disease states. Methods. This was a multicenter retrospective cross-sectional study of patients admitted with specified infectious diagnoses to two VA Medical Centers from 4/1/ 2019 to 7/1/2021. Patients were stratified into 4 cohorts for analysis;those with COVID-19, sepsis from respiratory source-(S-R), sepsis from non-respiratory source (S-NR), and respiratory source without sepsis (R). Electronic medical records were reviewed to collect the following: initial procalcitonin, cultures, SIRS criteria, comorbidities (CKD, ESRD, HF, immunosuppressed, surgery within the 7 days), and c-reactive protein. PCT elevation was defined as >=0.25 ng/mL. The frequency of positive cultures within 72 hours was evaluated for patients with elevated and normal PCT levels to determine the diagnostic performance of PCT overall and for each cohort. Results. 632 of 664 patients were evaluated in this study. PCT is elevated twice as often in the septic groups as compared to the non-septic groups (figure 1). Positive predictive value (PPV) varies from 27% to 63% as compared to negative predictive value (NPV) 53%-79% among the disease state groups (figure 2). Although small numbers, the NPV of PCT improves to 83% in patients with elevated temperature and white blood cells (WBC) (figure 3). Conclusion. The findings that NPV of PCT appears to be better than PPV, support current recommendations against using this as a diagnostic tool, but rather as a tool to assist with antibiotic de-escalation. Further studies are necessary to confirm whether there are specific markers such as temperature or WBC which may improve the NPV. Our data suggests PCT is less helpful in identifying the presence or absence of bacterial infection in septic versus non-septic patients. (Figure Presented).

A STUDY OF DISPROPORTIONATELY AFFECTED POPULATIONS BY RACE/ETHNICITY DURING THE SARS-COV-2 PANDEMIC USING MULTI-POPULATION SEIR MODELING AND ENSEMBLE DATA ASSIMILATION

The disparity in the impact of COVID-19 on minority populations in the United States has been well established in the available data on deaths, case counts, and adverse outcomes. However, critical metrics used by public health officials and epidemiologists, such as a time dependent viral reproductive number (Rt), can be hard to calculate from this data especially for individual populations. Furthermore, disparities in the availability of testing, record keeping infrastructure, or government funding in disadvantaged populations can produce incomplete data sets. In this work, we apply ensemble data assimilation techniques which optimally combine model and data to produce a more complete data set providing better estimates of the critical metrics used by public health officials and epidemiologists. We employ a multi-population SEIR (Susceptible, Exposed, Infected and Recovered) model with a time dependent reproductive number and age stratified contact rate matrix for each population. We assimilate the daily death data for populations separated by ethnic/racial groupings using a technique called Ensemble Smoothing with Multiple Data Assimilation (ESMDA) to estimate model parameters and produce an Rt(n) for the nth population. We do this with three distinct approaches, (1) using the same contact matrices and prior Rt(n) for each population, (2) assigning contact matrices with increased contact rates for working age and older adults to populations experiencing disparity and (3) as in (2) but with a time-continuous update to Rt(n). We make a study of 9 U.S. states and the District of Columbia providing a complete time series of the pandemic in each and, in some cases, identifying disparities not otherwise evident in the aggregate statistics. © American Institute of Mathematical Sciences.

Diagnostic conundrum in a patient with small cell lung cancer (SCLC)

Introduction: It is rare for pulmonary SCLC to present as a cavitating lesion unlike non-small-cell-cancer (NSCLC). Hence, if a cavitating lesion is found with histo-pathology showing SCLC, it is important to rule out alternate diagnosis e.g., infection [1]. Case: We present the case of a 41-year-old-male of Bangladeshorigin. He was referred on 2ww-pathway to UHL Glenfield hospital lung cancer team for haemoptysis. Clinical assessment (05/12/2019) revealed that he had 4kg weight loss/haemoptysis/anorexia/fatigue. He was a current smoker (10 pack-years) with no significant past/ family history. He worked in a restaurant. Clinical examination was unremarkable. Chest x-ray showed left-hilar-mass. CT scan revealed 3.2cm mass with peripheral cavitation and mild focal enhancement without calcification/mediastinal-lymphadenopathy. Differentials included cancer/rheumatoid arthritis/infection. Bloods including ANCA/ANA/rheumatoid factor and bronchial-washings microbiology/cytology were unremarkable. He was given antibiotics. He did not attend subsequent 2 out-patient-appointments. Repeat CT scan (March 2020) showed growing lesion with focally dilated vessel. CT-guided biopsy was advised but he declined it due to COVID19 pandemic. In May 2020, he agreed to undergo CT-guided biopsy. However, pre-procedure CT scan showed possible pseudoaneurysm. CT-guided biopsy was deemed high-risk and not attempted. Lung cancer MDT advised lobectomy given diagnostic dilemma. Patient declined surgery. CT in November 2020 showed progressive lesion. Patient still was not keen for surgery. He was admitted in June 2021 with haemoptysis. CT scan showed progressive cavitating disease with necrotic left hilar/mediastinal lymph nodes. He underwent EBUS-TBNA that confirmed SCLC. Given cavitating lesion and long history, left lower lobe lesion was deemed unlikely to be due to SCLC. He was referred to infectious disease (ID) clinic. Blood parasitology screen revealed positive Hydatid ELISA. He did not attend subsequent outpatient appointments in Oncology/ID clinics and has been discharged. Learning points: There were two pathologies: hydatid cyst (Fig. 1a);SCLC developed between November 2020 and June 2021 (Fig. 1b). 1) To look for cause of a cavitating lesion even if SCLC is diagnosed. 2) To consider hydatidcyst in lung-cavity differentials.(Figure Presented) Fig. 1

AACR President's initiative - 2020 by 2020: Democratizing precision cancer medicine and advancing health equity in the black belt

African Americans (AA) have higher incidence and mortality rates for several cancer types in comparison to their European American (EA) counterparts. Increasing participation in clinical research and patient registries, related to precision cancer medicine, will significantly improve cancer health equity. Many AA cancer patients are treated in community oncology clinics. Unfortunately, these health systems have limited access to Clinical Laboratory Improvement Amendments (CLIA) next generation sequence (NGS) germline and somatic DNA and RNA testing that are used to inform oncologists on the best treatment and/or clinical trial options for cancer patients. Indeed, AA CLIA NGS sample sets are poorly represented, which could presumably result in incomplete knowledge of genomic variants that could affect their treatment and overall outcomes. Hence, it is crucial to implement CLIA NGS efforts for all cancer patients. To address these disparities, Morehouse School of Medicine has formed the Comprehensive Approach to Reimagine health Equity Solutions (CARhES) consortium with Tuskegee University that has engaged community oncology practices in Alabama and Georgia - two of five Black Belt states. The CARhES consortium aims to implement precision cancer medicine to underserved and underrepresented communities that will improve the standard of cancer care by providing access to CLIA NGS testing, clinical trials, and personalized cancer care. Here we describe the first proof of concept of this approach with community oncology partners, i.e., Grady Health System, Wellstar Health System, Georgia Urology, Midtown Urology, and Maui Memorial Medical Center. At the time of consent, saliva, buccal, and tumor samples were collected from participants. Germline and somatic CLIA NGS was performed, and medical reports were returned to practitioners within 14 days. Prior to the COVID pandemic, the study enrolled over 880 patients with a 88% consent rate (n = 1000) in the first 11months of the program. At the start of the COVID pandemic, recruitment efforts were suspended for four months with a slow restart by June 2020. A decrease in the number of staff, office visits (67% reduction), and increase in COVID cases significantly limited recruitment efforts. During this slowdown, we established and improved eConsenting capabilities, which exist today. Community anxiety, due to the pandemic and SARS-CoV-19 vaccine efforts, resulted in a significant reduction in consent rates (88% to 60%). Nevertheless, this study began in April of 2019 and consented 1,750 participants in less than 2 years. Taken together, our study shows that a community-focused precision medicine approach requires meeting people where they are and providing them with access and understanding the benefit of clinical trial participation. The approximate 2,000 clinically annotated genomic AA datasets will greatly contribute to our understanding of cancer health disparities and among the first steps to democratize precision medicine.

PRIORITISATION IN THE UNITED KINGDON NATIONAL HEALTH SERVICE DURING A NATIONAL EMERGENCY: A QUALITATIVE CASE STUDY OF SURGICAL TEAMS' EXPERIENCES OF COLORECTAL CANCER SURGERY IN THE ACUTE EARLY STAGES OF THE COVID-19 PANDEMIC

Introduction The onset of the COVID-19 pandemic in early 2020 triggered reorganisation of hospital departments around the world as resources were configured to prioritise critical care. In spring 2020, NHS England issued national guidance proposing acceptable time intervals for postponing different types of surgical procedures for patients with cancer and other conditions. The 'Consider-19' study sought to investigate prioritisation decisions in practice, with in-depth examination of colorectal cancer surgery as a case-study, given recommendations that these procedures could be delayed by up to 12 weeks. Methods Twenty-seven semi-structured interviews were conducted with healthcare professionals between June - November 2020. A key informant sampling approach was used, followed by snowballing to achieve maximum regional variation across the UK. Data were analysed thematically using the constant comparison approach. Results Interviewees reported a spectrum of perceived disruption to colorectal cancer surgery services in the early phase of the pandemic, with some services reporting greater scarcity of resources than others. Nonetheless, all reported a need to prioritise patients based on local judgments. Prioritisation was framed by many as unfamiliar territory, requiring significant deliberation and emotional effort. Whilst national guidance provided a framework for prioritising, it was largely left to local teams to devise processes for prioritising within surgical specialities and then between different specialities, resulting in much local variation in practice. Discussion The pandemic necessitated a significant change in practice as surgeons, in a tense and uncertain situation, found themselves having to navigate clinically, emotionally, and ethically- charged decisions about how best to use limited surgical resources. Whilst unavoidable, many felt uncomfortable with the task and the consequences for their patients. The findings point to a need to better support surgeons tasked with prioritising patients and raise questions about who should be involved in this activity.

An Observational Study on the Humoral and Cellular Immune Response to SARS-CoV-2 mRNA Vaccination in Multiple Sclerosis and Other Autoimmune Neurological Disorders treated with Anti-CD20 Therapies

Objective: To assess adaptive immunity to SARS-CoV-2 in anti-CD20 treated individuals with mRNA vaccination as it relates to spike binding IgG, neutralizing antibody titers, and T cell response. Background: Anti-CD20 therapies attenuate humoral responses to vaccines. Their effect on T cell responses is unclear. We examined B and T cell responses with COVID-19 vaccination in patients receiving anti-CD20 therapy for multiple sclerosis (MS) and other autoimmune inflammatory neurologic diseases (AINDs). Design/Methods: Patients on anti-CD20 therapies were prospectively enrolled for longitudinal analysis of antibody and T cell responses before and after COVID-19 vaccination. Serum antibodies against the receptor-binding domain of the S1 spike protein (RBD-S1 IgG), neutralizing antibodies, and SARS-CoV-2 CD4 and CD8 T cell levels responses using activation-induced markers and INF-gamma release assay were measured at various time points including pre-vaccination, less than 12 weeks and greater than 12 weeks post initial vaccination series, and 4 and 12 weeks after 3rd “booster” vaccination. Results: Twenty-five MS and AIND participants are enrolled as of 10/11/21 with projected enrollment complete by December 2021 (50-60 total). Preliminary results for 17 of these patients (mean age 44 years-old, 83% female, 16 Pfizer, 1 Moderna) demonstrated attenuated RBD IgG antibody responses. However, CD8 T cell response is robust compared to non-immunosuppressed, age-matched controls (n=22) less than 12 weeks after two dose series (p value = 0.0069) and sustained long-term (>12 weeks) in all eight anti-CD20 patients tested thus far. Additional analysis will include comparison between pre and post 3rd vaccination at 4- and 12-week timepoints. Conclusions: Early results suggest that patients treated with anti-CD20 therapy generate a robust CD8 T cell response to SARS-CoV-2 mRNA post initial series of vaccination but remain with attenuated humoral immune responses. Our observational study will provide important data to guide vaccine management in patients on or anticipating anti-CD20 therapy.

Phage-like particle vaccines are highly immunogenic and protect against pathogenic coronavirus infection and disease.

The response by vaccine developers to the COVID-19 pandemic has been extraordinary with effective vaccines authorized for emergency use in the United States within 1 year of the appearance of the first COVID-19 cases. However, the emergence of SARS-CoV-2 variants and obstacles with the global rollout of new vaccines highlight the need for platforms that are amenable to rapid tuning and stable formulation to facilitate the logistics of vaccine delivery worldwide. We developed a "designer nanoparticle" platform using phage-like particles (PLPs) derived from bacteriophage lambda for a multivalent display of antigens in rigorously defined ratios. Here, we engineered PLPs that display the receptor-binding domain (RBD) protein from SARS-CoV-2 and MERS-CoV, alone (RBDSARS-PLPs and RBDMERS-PLPs) and in combination (hCoV-RBD PLPs). Functionalized particles possess physiochemical properties compatible with pharmaceutical standards and retain antigenicity. Following primary immunization, BALB/c mice immunized with RBDSARS- or RBDMERS-PLPs display serum RBD-specific IgG endpoint and live virus neutralization titers that, in the case of SARS-CoV-2, were comparable to those detected in convalescent plasma from infected patients. Further, these antibody levels remain elevated up to 6 months post-prime. In dose-response studies, immunization with as little as one microgram of RBDSARS-PLPs elicited robust neutralizing antibody responses. Finally, animals immunized with RBDSARS-PLPs, RBDMERS-PLPs, and hCoV-RBD PLPs were protected against SARS-CoV-2 and/or MERS-CoV lung infection and disease. Collectively, these data suggest that the designer PLP system provides a platform for facile and rapid generation of single and multi-target vaccines.

Diagnostic outcomes in suspected appendicitis before and during the COVID-19 pandemic

Introduction: Routine operative treatment of appendicitis was temporarily interrupted during the COVID-19 pandemic. Non-operative management in suspected appendicitis makes a definitive diagnosis difficult. This study investigated diagnostic outcomes of suspected appendicitis patients before and during COVID-19. Method: A retrospective review of patients aged 16-45 undergoing treatment for suspected appendicitis pre-COVID-19 (1st January 2019- 1st January 2020) and during the COVID-19 pandemic (1st March 2020 to 31st June 2020) was performed. Patients were followed up for one year (31st June 2021) to explore diagnostic outcomes. Results: At one year follow up, 206 patients were identified in the pre-COVID-19 cohort with 100% (n=206) undergoing an appendicectomy. On histopathological examination 77.2% (n=159) had appendicitis;10.7% (n=22) another pathology;2.9% (n=6) neuroendocrine tumour. There were 62 patients in the COVID-19 cohort in which 79% (n=49) underwent appendicectomy (56% (n=35) immediate appendicectomy;23% (n=13) interval appendicectomy). On histopathological examination 61% (n=38) had appendicitis;13% (n=8) another pathology;5% (n=3) neuroendocrine tumour. Of the remaining 13/62 patients, one had undergone a CT scan and colonoscopy for gastrointestinal symptoms demonstrating signs of chronic caecal inflammation treated conservatively. One underwent a CT scan alone for gastrointestinal symptoms finding no pathology. The remaining 11/62 patients had no further reported symptoms or diagnostics. Conclusions: This study demonstrates that the risk of appendiceal malignancy and chronic inflammation is important in non-operative management of suspected appendicitis and establishing consistent follow up pathways is essential.

MIC Shifts in Response to Increased Antibiotic Utilization during COVID-19 Pandemic

Background. Multiple studies have shown that antibiotic utilization increased during the COVID-19 pandemic. However, the impact of this increased utilization has not been well established. The aim of this study is to describe the trends in minimum inhibitory concentrations for various antibiotics against common gram-negative pathogens observed since the start of the COVID-19 pandemic as compared to previous years. Methods. This retrospective study was conducted at the Memphis VA. All respiratory, urine, and blood culture MicroScan results run from October 2017-March 2021 were analyzed. Only inpatient and emergency department data was included. The MIC50 and MIC90 of seven antibiotics for four of the most common pathogens were trended by quarterly intervals. Results. MIC50 and MIC90 were compared using standardized breakpoints. As compared to previous years, Pseudomonas aeruginosa was noted to have the most sustained increase in MIC90 across various antibiotics. In the last 3 quarters of the study time frame, piperacillin-tazobactam mean MIC90 increased from 32 to 64, cefepime from 8 to > 16, and meropenem from 4 to > 8. Escherichia coli had a sustained increase in ceftriaxone MIC90 from < 1 to > 8 in the final quarter of 2020 and beginning of 2021. Klebsiella pneumonia was also found to have a sustained increase in cefepime mean MIC90 from < 1 to > 16 during the year of 2020, with return to previous MIC90 the following quarters. Conclusion. Previous studies have clearly demonstrated a widespread increase in antibiotic utilization during the COVID era. Our study demonstrates how even short-term increases in antibiotic use can lead to shifts in MIC, if not outright resistance. This was demonstrated across multiple common gram-negative pathogens and to various broad-spectrum antibiotics which were commonly used more frequently during COVID-19. Further analysis will be needed to determine whether these trends continue or whether the decrease in antibiotic utilization in the recent months will lead to similar decrease in MIC.