Altered immune response to vaccination in patients with plasma cell premalignancy

Introduction Patients with hematological malignancies, including multiple myeloma (MM), experience suboptimal responses to SARS-CoV-2 vaccination. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) are precursors to MM and exhibit altered immune cell composition and function. The SARS-CoV-2 pandemic and the subsequent population-wide vaccination represent an opportunity to study the real-life immune response to a common antigen. Here, we present updated results from the IMPACT study, a study we launched in November 2020 to characterize the effect of plasma cell premalignancy on response to SARS-CoV2 vaccination (vx). Methods We performed: (i) ELISA for SARS-CoV-2-specific antibodies on 1,887 peripheral blood (PB) samples (237 healthy donors (HD), and 550 MGUS, 947 SMM, and 153 MM patients) drawn preand post-vx;(ii) single-cell RNA, T cell receptor (TCR), and B cell receptor (BCR) sequencing (10x Genomics) on 224 PB samples (26 HD, and 20 MGUS, 48 SMM, and 24 MM patients) drawn preand post-vx;(iii) plasma cytokine profiling (Olink) on 106 PB samples (32 HD, and 38 MGUS and 36 SMM patients) drawn pre- and post-vx;and (iv) bulk TCR sequencing (Adaptive Biotechnologies) on 8 PB samples from 4 patients (2 MGUS, 2 SMM) drawn pre- and post-vx. Results Patients with MGUS and SMM achieved comparable antibody titers to HD two months post-vx. However, patient titers waned significantly faster, and 4 months post-vx we observed significantly lower titers in both MGUS (Wilcoxon rank-sum, p=0.030) and SMM (p=0.010). These results indicate impaired humoral immune response in patients with MGUS and SMM.At baseline, the TCR repertoire was significantly less diverse in patients with SMM compared to HD (Wilcoxon rank-sum, p=0.039), while no significant difference was observed in the BCR repertoire (p=0.095). Interestingly, a significant increase in TCR repertoire diversity was observed post-vx in patients with SMM (paired t-test, p=0.014), indicating rare T cell clone recruitment in response to vaccination. In both HD and patients, recruited clones showed upregulation of genes associated with CD4+ naive and memory T cells, suggesting preservation of the T cell response in SMM, which was confirmed by bulk TCR-sequencing in 4 patients.Lastly, by cytokine profiling, we observed a defect in IL-1beta and IL-18 induction post-vx in patients with SMM compared to HD (Wilcoxon rank-sum, p=0.047 and p=0.015, respectively), two key monocyte-derived mediators of acute inflammation, suggesting an altered innate immune response as well. Conclusion Taken together, our findings highlight that despite the absence of clinical manifestations, plasma cell premalignancy is associated with defects in both innate and adaptive immune responses. Therefore, patients with plasma cell premalignancy may require adjusted vaccination strategies for optimal immunization.

Change management: a framework for adaptation of the change management model

Digital health change management projects have a high rate of failure which limits the realization of their potential benefits. While there are many change management models, there is limited evidence of one model being effective in all circumstances. We propose a framework for building on an organizations preferred change management model and adapting it based on the change desired and the organization. We use three change management scenarios (small, large, and rapid) from radiology to explore the application of the framework. Radiology was chosen to illustrate the framework because it has been digital longer than many medical specialties. Given the high number of upgrades and new digital platforms in Radiology, it could also serve as a testing ground for such a framework. © 2023 "IISE”.

Virtual Clinical Outcome Ascertainment in a Prostate Cancer Treatment Trial

Introduction/Objective: The COVID-19 pandemic stopped site visits for clinical outcome data collection in March 2020. We utilized several remote methods to collect data and assessed their relative effectiveness. Background(s): The ProtecT randomized trial (Prostate cancer testing and treatment trial) aimed to determine the effectiveness of active monitoring (surveillance), radiation and surgery for localized disease. The primary outcome is prostate cancer mortality with clinical secondary outcomes of disease progression and metastasis. There was no difference in the primary outcome at 10 years (published in 2016) between groups (differences in metastasis and functional problems) so followup was extended to 15 years (November 2020). Method(s): The 10-year analysis used annual paper case report forms (CRFs) completed by research nurses based at UK hospitals. In extended follow-up, it was intended that National Health Service routine data would identify participants with potential disease progression. Prior to the pandemic the research nurse reviewed electronic health records at eight English hospitals and completed an eCRF in REDCap software. It became unlikely that site visits were going to be possible in 2020. A shortened eCRF was created focussed on essential outcome data and site staff agreed to help collect clinical data in July 2020. Result(s): Ethical approval for extending the study end date and the sponsor updating GDPR terms of site agreements were delayed by COVID-19 research taking priority. This also prevented the research nurse updating their NHS Research Passport for Honorary Contracts to access sites. Approvals were gained in December 2020. At four sites, local staff completed REDCap eCRFs with support from the data manager and research nurse by email and virtual calls. The research nurse gained remote access to hospital electronic health records at three sites by April 2021, which required extensive research governance approvals, training on hospital IT systems and their software on multiple laptops. At one site, from December 2020, 2-h virtual calls were held with local staff who interrogated electronic medical records as trial staff completed REDCap eCRFs. On average, 15 note reviews were conducted each call which were planned around clinical commitments. Secondary clinical outcomes were collected remotely for 94% of participants in follow-up (1395/1474). There was no difference in the three methods: remote hospital record access 594/601 (98.8%);local staff completion 575/600 (95.8%);and online calls 215/221 (97.3%) although less data cleaning was required as data queries were resolved during calls. Benefits also included savings on time traveling to sites and accommodation and local clinical staff could access a wider range of health records and information outside their hospital. However, enabling remote data capture delayed data analysis by 6 months. Conclusion(s): In a prostate cancer treatment trial remote data capture of clinical outcomes was successful as site visits became impossible due to the pandemic. Online methods were tailored to sites requirements but required substantial preparation and governance approvals.

A Functional Assay to Measure the T Cell Response to Sars-Cov-2 in Primary Immunodeficiency Patients

Background/Aims Effective symptom management may require the use of medications. Medication adherence may be hindered by formulation aspects, such as poor taste. Paediatric studies indicate, that despite concerns of swallowing solid dose forms, children prefer these to liquid forms. They find the solid dose forms more palatable. However, swallowing numerous solid dose forms, may present a significant 'pill' burden to patients and their care-givers. Filling empty gelatine capsules with requisite medications is seen and used as a way to address palatability, decrease pill burden and thereby increase compliance. Yet there is little evidence on the impact this practise may have on the effectiveness of over-encapsulated medicines. This study explored the effect of over-encapsulation on in vitro disintegration and dissolution, of some commonly used medicines in paediatric palliative care. Method Immediate release (Cyclizine Hydrochloride, Gabapentin, Paracetamol) and modified release preparations (Omeprazole, Diclofenac sodium) were over-encapsulated in size 00 gelatin and HPMC capsules (n=6). Dissolution and disintegration were tested according to Pharmacopeia standards. Statistical analyses, using Student's T-test and f1 and f2 tests (respectively) were applied to determine similarities or differences in disintegration or dissolution. Results Disintegration and dissolution was prolonged for all over-encapsulated immediate release preparations, especially when using HPMC capsules. However, percentage of drug dissolved met the acceptance criteria for immediate-release solid oral dosage. Over-encapsulation of modified release preparations did not lead to significant dissolution or disintegration changes. Conclusion Over-encapsulation, may delay medication release, especially for immediate release medicines however, medicine effectiveness may not be. Further studies are required before we can safely recommend use of over-encapsulation as an administration compliance aid.

Outcomes of Pregnant Women Exposed to Sotrovimab for the Treatment of COVID-19 in the Omicron Predominant Era (PRESTO)

Background. Sotrovimab, a monoclonal antibody with efficacy against SARS-CoV-2 including certain Omicron variants, has been used in treatment of mildmoderate COVID-19. Limited data exists regarding its use in pregnant women. Methods. Electronic medical record review of pregnant COVID-19 patients treated with sotrovimab from 12/30/21-1/31/22 (Yale New Haven Health Hospital System [YNHHS]) was performed. Included were pregnant individuals >= 12 years, weighing >= 40 kg, with positive SARS-CoV-2 test (within 10 days). Those receiving care outside YNHHS or receiving other SARS-CoV-2 treatment were excluded. We assessed demographics, medical history, and Monoclonal Antibody Screening Score (MASS). Clinical outcomes assessed included emergency department (ED) visit < 24 hours, hospitalization, ICU admission, and/or death within 29 days of sotrovimab. Pregnancy and neonatal outcomes were assessed until 8/15/22. Results. Among 22 subjects, median age was 32 years and body mass index was 27 kg/m2. Sixty-three percent were Caucasian, 9% Hispanic, 14% African-American, and 9% Asian. Nine percent had diabetes and sickle cell disease. Five percent had wellcontrolled HIV. Eighteen percent, 46%, and 36% received sotrovimab in trimester 1, 2, and 3, respectively. No infusion/allergic reactions occurred. MASS values were < 4. Only 12/22 (55%) received complete primary vaccination (46% mRNA-1273;46% BNT162b2;8% JNJ-78436735);none received a booster. There were no ICU admissions nor deaths. One subject was hospitalized for post-partum pyelonephritis;another had an ED visit for post-partum vaginal bleeding. Median gestational age at birth was 38.9 weeks. Nine percent had premature labor and premature rupture of membranes, respectively. Median infant birth weight was 3220 g. One neonate required an ICU stay due to prenatally diagnosed omphalocele (before sotrovimab) in a mother with congenital defect history. There were no abortions, fetal loss, or other birth/neurodevelopmental defects. Conclusion. Pregnant COVID-19 patients receiving sotrovimab at our center tolerated it well with good clinical outcomes. Pregnancy and neonatal complications did not appear sotrovimab-related. Though a limited sample, our data helps elucidate the safety and tolerability of sotrovimab in pregnant women.

Deep Single-Cell, Proteogenomic Insights from Sars-Cov-2 Infected Lung Tissues

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease 2019 (COVID-19) and is likely to lead to complexities in treating thoracic malignancies. Patients with lung cancer are at an increased risk of becoming infected with the SARS-CoV-2 virus and experience higher morbidity and mortality than the general population. However, little is known about the host tissue and cellular responses associated with SARS-CoV-2 infection, symptoms, and disease severity. Methods Here, we use the Nanostring GeoMX Digital Spatial Profiler (DSP) and CoxMX Spatial Molecular Imager (SMI) technology to determine tissue signatures, and spatially resolved quantitative single-cell proteogenomic changes driven by SARS-CoV-2 infection. This dual approach was used to generate an in-depth picture of the pumonary transcriptional and proteomic landscape of COVID-19, pandemic H1N1 and uninfected control patients.1 Rapid autopsy COVID-19 lung samples were collected across two independent cohorts of patients, and tissue microarrays (TMAs) were prepared. For GeoMx, n=10 COVID-19, n=10 pH1N1 and n=5 normal control tissues were compared. For CosMx, n=19 COVID-19 cores in technical replicates, and n=20 normal control tissues were compared. Tissue-based gene signatures were subsequently tested in the peripheral samples from COVID-19 patients. Results SARS-CoV-2 viral presence was confirmed by RNAscope and integrated to inform region of interest and cell types involved in infection. Analysis of the Nanostring GeoMx data revealed tissue signatures associated with SARS-CoV-2 infection, including Type 1 IFN, blood coagulation, hypoxia and angiogenesis. Analysis of the Nanostring CosMx data enabled single cell typing and mapping of tissue-specific signatures to cellular compartments of interest (e.g. macrophages, fibroblasts) and investigation of complex cell population heterogeneity and interactions. All these while preserving spatial context and highlighted differential cell type distribution in the lungs of COVID-19 patients compared to non-infected controls. Our tissue-based Type 1 IFN signatures, when tested in the blood, were found to be predictive of disease severity in COVID-19 patients when measured within the first few days of symptom onset. Conclusions Here, we've used innovative, cutting-edge spatial transcriptomics approaches to delineate tissue signatures and cellular profiles unique to COVID-19 and common across acute respiratory distress syndrome. These data will aid in understanding the proteogenomic landscape of SARS-CoV-2 infected lung tissues and form new knowledge for the impact on thoracic malignancies, and treatments such as immunotherapy. Moreover, the study demonstrates how tissue-based findings can be rapidly developed into signatures tested in noninvasive samples.

Closing the care gap with wearable devices: Innovating healthcare with wearable patient monitoring

Patient-focused healthcare, driven by COVID-19 experiences, has become a hallmark for providing healthcare services to patients across all modalities of care and in the home. The ability to capture real-time patient data, no matter the location, via remote patient monitoring, and to transmit that data to providers and organizations approved by the consumer/patient, will become a critical capability for all healthcare providers. Of all the remote patient monitoring product designs, wearable medical devices are emerging as the best positioned to support the evolving patient-focused healthcare environment. This book is for those who are evaluating, selecting, implementing, managing, or designing wearable devices to monitor the health of patients and consumers. This book will provide the knowledge to understand the issues that mitigate the risk of wearable technologies so people can deliver successful projects using these technologies. It will discuss their use in remote patient monitoring, the advantages and disadvantages of different types of physiological sensors, different wireless communication protocols, and different power sources. It will describe issues and solutions in cybersecurity and HIPAA compliance, as well as setting them up to be used in healthcare systems and by patients. © 2023 Michael W. Davis, Michael J. Kirwan, Walter N. Maclay and Harry P. Pappas. All rights reserved.

Urologic Adverse Events of the COVID-19 Vaccination

Introduction &Objective: There have been anecdotal reports of adverse events associated with the COVID-19 vaccine, especially within media coverage of the vaccine's initial rollout. We aim to quantify and analyze urologic adverse events and symptoms after COVID-19 vaccination. Method(s): We queried the FDA Vaccine Adverse Event Reporting System (VAERS) for all reported symptoms following COVID-19 vaccination, as well as following any vaccination, for the period of December 2020 through April 1st, 2022. We identified fifteen common adverse urologic events. Using proportional reporting ratio (PRR) and reporting odds ratio (ROR), we analyzed the reporting data in the VAERS database. Result(s): A total of 6,027,972 vaccinations, including 3,666,529 COVID-19 vaccinations were identified from the queried period with 1,560,835 and 803,169 adverse events reported, respectively. Out of all adverse event reports reported following COVID-19 vaccination, the most common adverse event was urinary tract infections which only accounted for 2,263 adverse events. The median age of the patients reporting urologic symptoms was 50 years old (IQR 22-64) and 66% of the patients were female. Conclusion(s): Urologic symptoms reported after COVID-19 vaccination continue to be extremely rare in total number but furthermore, none of the adverse urologic events had positive signals. Although there have been anecdotal reports of adverse events associated with the COVID-19 vaccine, a review of the VAERS database did not find any positive signals. Our findings suggest these adverse events are not related to the COVID-19 vaccine but further evaluation and analysis are ongoing.

Multisectoral Factors Associated with Global National Trends in Neonatal Mortality Rates: A Call for Targeted Public Health Intervention, Particularly in Countries Impacted Most by COVID-19

Background: The United Nations' 2030 Sustainable Development Goals (SDGs) target an end to preventable newborn deaths and a reduction in neonatal mortality rate (< 28 d, NMR) to 12/1,000 live births for all countries. Understanding concurrent trends in country-level, multisectoral factors associated with NMR trends may illuminate opportunities for intervention strategies. Our objective was to explore country-specific trends in NMR from 1990-2019 and identify those countries which contribute to the largest percentage of neonatal deaths in order to focus efforts on reducing NMRs in those specific countries. Unfortunately, due to the COVID-19 pandemic, the 2030 SDGs have been severely impacted. Methods: We created a comprehensive global database of NMR and associated variables that were selected based on literature review and categorized into Population Health, Health Systems, Maternal, Neonatal, and Social factors from 1990 to 2019. Data were compiled from publicly available sources including UNICEF, World Bank, WHO, and OECD. Data were collected and analyzed for 195 countries. NMR trends were analyzed from 1990 to 2019 with more targeted analysis of trends in the last 2 decades from 2000 to 2019. We then performed statistical analyses using the selected variables to compare variable means using t-tests, identify bivariate associations, and generate multivariable regression models. Results: In terms of total deaths, 20 countries contributed 75% of the total 2.5 million neonatal deaths. All of these 20 countries showed decreases in NMR since 1990 (Figure 1). However, only China and Egypt accomplished the UN goal of reducing NMR to 12/1,000 live births. We compared variables associated with NMR in our 20 target countries to the remaining countries and found significant differences between the means for most variables (Table 1). Bivariate regression analyses showed statistically significant associations between NMR trends and changes over time in median income, health care spending, literacy level, maternal mortality ratio, and low birthweight rate. Ultimately the variables maternal mortality ratio change and median income change were selected for multivariable analysis based on collinearity. The multivariate regression model generated using NMR, maternal mortality ratio change, median income change resulted in an r-squared value of 0.54, explaining 54% of the variance in NMR trends. Conclusion: Since 20 countries contribute 75% of the neonatal deaths worldwide, we propose that targeting these 20 countries would have the greatest impact on global neonatal deaths. Future research will focus on identification of country specific barriers and evaluating the countries with greatest NMR improvements to propose effective focused strategies for reducing NMRs in high burden countries. The disparate impact that COVID-19 has had on countries with the highest neonatal mortality burden should be a primary focus of continued public health invention efforts, and is a specific focus of our ongoing research.

Process Development and Manufacturing: A SUPPLY CHAIN CRISIS STORY: CULTURE BAG SHORTAGE ENFORCED VALIDATION OF AN ALTERNATIVE EXPANSION SYSTEM FOR CAR T CELLS

Background & Aim: The recent supply chain crisis highlights a need to establish alternative manufacturing (MFG) protocols ensuring continuity of existing and new cell therapy (CT) clinical trials. Our academic CT program, and likely others, experienced purchasing delays and restrictions caused by diversion of critical supplies to meet COVID-19- related research demands and/or reduced vendor capacity due to resource constraints, including attrition of skilled workforce. Mitigation strategies aimed at creating process redundancies overcome production challenges resulting from a scarcity of goods. Here, we validated an alternative ex vivo culture system to clinically MFG lentiviral vector (LV) modified CAR T cells due to limited availability of cell expansion culture bags for the Wave bioreactor, a critical unit of operation that we have used to successfully MFG thousands of gene-modified T cell products for 30+ clinical trials. Methods, Results & Conclusion: The disposable G-REX culture vessels were compatible and seamlessly integrated with our closed system platform. Mesothelin CAR T cells were manufactured in parallel via the G-REX or conventional Wave bioreactor using consented patient starting material. Critical quality attributes of the final T cell products, including viability, transduction efficiency, phenotype and function were assessed. Transduction efficiencies assessed by flow cytometry and/or molecular qPCR were lower in products generated in the G-REX compared to the wave using the same multiplicity of infection. However, at least 50-fold expansion was achieved, with cell viabilities greater than 90% and with comparable cellular phenotypes. The Meso CAR T cells generated by either process were capable of eliciting CAR-mediated cytotoxicity and effector cytokine production. Strikingly, 2-4 billion T cells were harvested from a starting seed number of just 50 million T cells in the 1L G-REX, which may be sufficient to meet most protocol- specified cell therapy doses, suggesting that a full apheresis collection may not be needed. Notably, this process required just 1/3 of the starting material, 1/5 of the media and decreased manual effort through culture duration compared to the Wave. Additionally, the reduced reliance on specialized capital equipment combined with a small footprint enables simultaneous MFG of several immunotherapy products. These advantages propose consideration in replacement of current expansion platform as well as validating an alternative process for MFG CAR T cells.

COVID-19 and the Case for a National Food Emergency Stockpile

Food insecurity in the United States is not a new challenge, but the coronavirus pandemic has revealed that the current system to sup-port Food Assistance Providers (FAPs) is incredibly brittle and vul-nerable to supply chain disruptions. Many FAPs       use            just-in-time models to support their operations, relying heavily on donations from restaurants and grocers. However, COVID-19 has demon¬strated that when a disaster causes increased food demand and widespread destabilization of food supply chains, jurisdictions are severely constrained from obtaining and delivering food to pop¬ulations in need. Recent events have further amplified a potential danger to current food security strategies in terms of regions expe¬riencing multiple events, such as a pandemic coupled with hurri¬canes, wildfires, or other catastrophes. After exploring the current governmental food security measures, their long-term deficiencies, and other lessons learned through the COVID-19 response, we call for a major policy shift in how the country addresses food insecurity following a disaster. Rather than relying on after-the-fact spending and hastily created infrastruc¬ture, the nation should proactively stockpile shelf-stable food. To this end, we propose establishing a national stockpile of shelf-sta¬ble foods to help protect against future food supply destabilization. © 2020, Policy Studies Organization. All rights reserved.

SINGLE-CELL IMMUNE PROFILING AND REPERTOIRE ANALYSIS OF CONVALESCENT PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND SARS-COV-2 ANTIBODY RESPONSE

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by immune dysregulation and decreased T cell receptor (TCR) repertoire diversity. Patients with immune-mediated disorders such as IBD have attenuated convalescent antibody responses after COVID-19 infection. We sought to understand the immune configuration associated with high versus low convalescent SARS-CoV- 2 antibodies in patients with IBD using single-cell immunophenotyping. Methods: We performed a study of 9 patients with IBD who were SARS-CoV-2 convalescent (recovered from COVID-19 and converted RNA positive to negative) and 9 matched SARS-CoV-2 naïve controls (no prior COVID-19, confirmed RNA negative). We measured plasma SARS-CoV- 2 antibody (N protein IgG, S1RBD IgG, S1RBD IgA) levels from patients with IBD two months after recovering from COVID-19 (RNA negative). We selected three patients with the highest SARS-CoV-2 antibodies and three matched (for age, sex, IBD subtype and disease activity, medications, COVID-19 severity) patients with the lowest antibodies and performed their peripheral blood mononuclear cell (PBMC) single-cell transcriptomics with paired TCR and BCR sequencing using 10X Genomics. Normalization, dimensionality reduction, and clustering were performed using Seurat. TCR and BCR immune repertoire analyses were performed using Immunarch. Results: SARS-CoV-2 convalescent patients with IBD had detectable but variable SARS-CoV-2 antibody levels (range 0-469 U/mL), whereas SARSCoV- 2 naïve IBD patients had no detectable antibodies. The mean SARS-CoV-2 antibody concentration among the three IBD patients with the highest and three patients with the lowest groups differed by more than 10-fold (206.0 vs 17.5 U/mL, P<0.001). PBMC singlecell immunophenotyping revealed decreased naïve CD4+ T cell and increased CD14+ monocyte and memory CD4+ T cell proportions in IBD patients in the low versus high SARSCoV- 2 antibody group. There were higher numbers of HLA-DQA1+ B cells and CD8 T cells and lower GPR183+ B cells and CD8 T cells in the high SARS-CoV-2 antibody group. There was a trend towards decreased TCR and BCR repertoire diversity in the low SARS-COV-2 antibody group. Finally, we identified immunoglobulin gene signatures (IGHV1-69D/IGLV3- 25, IGHV3-48, IGHV3-7/IGKV41/IGLV1-47, IGHV3-7/IGKV4-1, IGHV3-7/IGKV4-44) that were enriched only in the high SARS-CoV-2 antibody group. Conclusions: Single-cell immunophenotyping of PBMC from convalescent patients with IBD reveal differences in CD4+ T cell, CD14+ monocyte, and HLA-DQA1+ and GPR183+ B and CD8 T cell immunophenotypes, immune repertoire diversity, and immunoglobulin gene signatures in patients with high versus low SARS-CoV-2 antibody levels.(Figure Presented)Figure 1. SARS-COV-2 Antibodies in Convalescent Patients with IBD and Single-Cell Immunophenotypes. A) SARS-COV-2 antibody levels in COVID-19 convalescent versus SARS-CoV-2 naïve patients with IBD B) T-SNE plot of PBMC immunophenotypes in all convalescent patients with IBD C) Differences in proportion of single-cell PBMC immunophenotypes in high versus low SARS-COV-2 antibody patients D) Differences in HLA-DQA1 and GPR183 immunophenotypes in high versus low SARS-COV-2 antibody patients.

Classification of COVID-19 Disease Severity using CT Scans via Deep Convolutional Neural Networks

The respiratory virus Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), commonly known as COVID-19, has caused wide concern and a need to be able to accurately determine its effects on individual lung capacities. Computerized Tomography (CT) scans were chosen as the main datatype for determining whether a patient had COVID-19 or had normal lung capacities. The rationale is that there is an inherent lack of CT scan experts, especially in counties with low socio-economic status (SES). Thus, an automated and objective artificially intelligent (AI) algorithm can assist in the hope to provide more efficacious use CT scans for classification of COVID-19 and monitoring of disease progression. In this study, a wide variety of CT scans with different formats were tested to determine the best approach for binary classification models using deep learning (DL) techniques. A total of three publicly available COVID-19 datasets were tested using a 2-dimensional and a 3-dimensional algorithm, where each dataset had its own subsets and unique parameters. A finalized version of the 3-dimensional model was shown to achieve a high accuracy, precision, sensitivity, and F1 Score of 86.6% each. The developed method provides an objective measure to automatically classify COVID-19 patients from CT scans © 2022 IEEE.

Dose-Dependent Respiratory Viral Inhibition by a Safe Inhaled Alkaline Treatment

Introduction: SARS-CoV-2 respiratory infection is pandemic and continues to cause significant mortality and morbidity worldwide. Respiratory viral infections in general are a leading cause of hospital admissions and mortality throughout the world as well. Most respiratory viral infections require an acidic intracellular and endosomal environment in order to enter host cells, replicate, and cause illness. We study the beneficial effects of airway alkalinization by an inhaled drug, Optate, that we currently have demonstrated is safe to inhale by healthy subjects and those with stable airways disease. We have recently shown that treatment with 4.5 mg/ml Optate safely inhibits SARS-CoV-2 infection in primary human airway epithelial cells (HAECs). We hypothesized that this inhibition would be dose dependent and that Optate would also inhibit other viral infections in a dosedependent manner. Methods: HAECs were infected with respiratory syncytial virus with green fluorescent protein (RSV-GFP) or SARS-CoV-2 virus. A dose-response curve of Optate was performed in each infection model and compared to a control group. Viral infection was quantified using fluorescence microscopy, plaque assays, and viral protein quantification. Optate pH was measured at each dose and a corresponding dose/pH curve was calculated to compare pH to dose-response. Results: SARS-CoV-2 infection was significantly inhibited by doses of Optate > 2.25 mg/ml, corresponding with an Optate pH > 9.2 (n = 4, p < 0.001). RSV infection was significantly inhibited by doses of Optate > 2 mg/ml, corresponding with an Optate pH > 9 (n = 3, p < 0.001). No significant difference was noted between control and Optate treated HAECs at lower concentrations of Optate. Conclusions: Optate inhibits SARS-CoV-2 and RSV viral infections in a dose-dependent manner that correlates with Optate pH. These findings suggest that Optate may be an inhaled therapeutic for patients with respiratory viral infections. (Table Presented).

ANXIETY DURING THE COVID-19 PANDEMIC: PRELIMINARY FINDINGS FROM THE UCSF ASPIRE STUDY

OBJECTIVE: To describe the prevalence of anxiety symptoms in early pregnancy and identify predictors of early pregnancy anxiety during the COVID-19 pandemic. MATERIALS AND METHODS: We assessed baseline moderate-to-severe anxiety symptoms after enrollment into the UCSF ASPIRE (Assessing the Safety of Pregnancy in the Coronavirus Pandemic) Prospective Cohort from May 2020 through February 2021. Pregnant persons <10 weeks' gestation completed questions regarding sociodemographic characteristics, obstetric/ medical history, and pandemic-related experiences. Chi-square and multivariate hierarchical logistic regression analyses determined predictors of moderate or severe anxiety symptoms (GAD-7 R10). All analyses performed with Statistical Analysis Software (SAS®) version 9.4. RESULTS: 4,303 persons completed the GAD-7 questionnaire. The mean age of this nationwide sample was 33 years and 25.7% of participants received care through a fertility clinic. 12.6% of pregnant persons reported moderate-to-severe anxiety symptoms. On univariate analysis, less than a college education (p<0.0001), pre-existing history of anxiety (p<0.0001), and history of prior miscarriage (p=0.0143) were predictors of moderate-to-severe anxiety symptoms;care at a fertility center was protective (26.6% vs 25.7%, p= 0.0009). COVID-19 related stressors were strongly predictive of anxiety in pregnancy (p<0.0001). Race/ ethnicity and a prior history of live birth were not predictors of moderate- to-severe anxiety. In the hierarchical logistic regression model, pre-existing history of anxiety remained associated with anxiety during pregnancy. While education was no longer significant, there was a trend towards this being predictive. Hierarchical Logistic regression predicting moderate to severe anxiety symptoms CONCLUSIONS: Pre-existing history of anxiety and low maternal educational attainment likely exacerbated the contribution of stressors due to the COVID-19 pandemic on early pregnancy anxiety. IMPACT STATEMENT: Socioeconomic disparities may exacerbate the contribution of pandemic-related stressors to early pregnancy anxiety risk. With limitations in prenatal care administration during the pandemic, continued emotional health support should remain an important focus for providers.

VIRTUAL AND IN-PERSON CARE DURING THE COVID-19 PANDEMIC LED TO EQUIVALENT PATIENT SATISFACTION FOR REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY (REI) PATIENTS

OBJECTIVE: To evaluate whether a shiftto virtual care during the COVID-19 pandemic negatively impacted patient satisfaction among REI patients. MATERIALS AND METHODS: A modified version of a validated multiple-choice survey assessing satisfaction with care was sent to current patients who agreed to participate in research at a tertiary medical center. The survey evaluated satisfaction with multiple aspects of care. Respondents were categorized by visit type: in-person only (n=23), virtual-only (n=12), and a mix of both settings (n=52). Responses were dichotomized into “Agree” or “Disagree”, with neutral grouped with “agree”. Chi-squared tests of independence to assess differences between groups were conducted in R (Version 3.4.4). P<0.05 was interpreted as statistically significant. The study was approved by the University of California San Francisco Institutional Review Board. RESULTS: Out of 1282 patients who received an invitation to participate, 526 patients (41.0%) completed our survey. Eighty-seven of these were seen by the Division of REI and included in this study. Median participant age was 36.5 (range: 21-76). There were no significant differences in respondents' satisfaction with the type of care received (in-person vs. virtual vs. mixed, p=0.43). There were no statistically significant differences in respondents' ability to develop a relationship with their provider (p=0.25), provider's friendliness (p=0.50), skills or knowledge (p=0.71), and concern (p=0.80) as rated by respondents. The frequency of visits starting on time (p=0.50), convenience of the visit date and time (p=0.78), and the amount of time spent with the provider (p=0.89) were also similar across all three groups. Although 56% of respondents who had mixed care reported that virtual visits may have compromised their health, this was not shown in either the virtual-only or in-person only groups, introducing the possibility of a confounder. Sixty-eight percent of respondents seen virtually were likely to recommend virtual visits to others. When asked about preferences for primary visit type after the COVID-19 pandemic, at least 50% of participants in all groups preferred in-person visits, with a minority choosing virtual visits (22%), alternating between virtual and in-person (16%), or expressing no preference (5%). CONCLUSIONS: A shift to virtual care during the COVID-19 pandemic did not appear to impact patient satisfaction with the care received as patients were highly satisfied regardless of the setting in which they received care. A majority of patients seen virtually were likely to recommend virtual visits to others. Nonetheless, a plurality of patients in all three groups preferred their primary visit type to be in-person. IMPACT STATEMENT: This study shows no significant differences in patient satisfaction regardless of visit type. Further research is needed to understand how to optimize virtual care delivery after the COVID-19 pandemic.

A STUDY INVESTIGATING EXPERIENCES OF RADIOGRAPHERS IN EUOPRE DURING THE COVID19 PANDEMIC

Radiographers have been frontline health professionals throughout the COVID-19 pandemic. They are amongst the first line that may be dealing with infected persons and have gained invaluable experience in dealing with a pandemic. Aims: To record and provide a contemporaneous account of the roles and experiences of radiographers during the pandemic for posterity. Radiographers were contacted remotely and asked to submit their reflections of working as a radiographer during the COVID-19 pandemic. All members of the EFRS were invited to partake in our project both directly by our research team and via a memo that the EFRS sent to their member societies. Information relating to the project was widely circulated on twitter. Reflections were welcome in any form. The information collected was deposited in the UCD archives. To date, two submissions have been received. Reflections were qualitatively analysed using the Braun & Clark six step method. Themes generated from the reflections submitted included adaptability, pride and gratitude for the healthcare system, and togetherness. Clinical radiographers reported a sense of pride in their work as patients appreciated their presence. A sense of gratitude for being part of a cherished healthcare systemwas reported. Academic radiographers reported a sense of togetherness as students and professors alike adapted to the new challenges of online learning. Although this research is still ongoing, preliminary indications are that the information obtained yielded an account of the experiences of the radiographer in Europe and the UK during the pandemic and will provide important material for students and future researchers.