SARS-CoV-2 infection disrupts trophoblast function and placental syncytial barrier integrity via its accessory protein, ORF3a

Problem: Although it is rare for a SARS-CoV-2 infection to transmit vertically to the fetus during pregnancy, there is a significantly increased risk of adverse pregnancy outcomes due to maternalCOVID- 19. However, there is a poor understanding of such risks because mechanistic studies on how SARS-CoV-2 infection disrupts placental homeostasis are significantly lacking. The SARS-CoV-2 proteome includes multiple structural and non-structural proteins, including the non-structural accessory proteinORF3a. The roles of these proteins in mediating placental infection remain undefined. We and others have shown that autophagy activity in placental syncytium is essential for barrier function and integrity. Here, we have used clinical samples and cultured trophoblast cells to evaluate syncytial integrity of placenta exposed to SARS-CoV-2. The objective of our study was to investigate potential mechanisms through which SARS-CoV-2 impairs placental homeostasis and causes adverse pregnancy outcomes. We tested the central hypothesis that an essential SARS-CoV-2 non-structural and accessory protein, ORF3a, uniquely (amongst multiple viral proteins tested) with a novel three-dimensional structure andwith no homology to any other proteins is a key modulator of placental trophoblast cell dynamics via autophagy and intracellular trafficking of a tight junction protein (TJP), ZO-1. Method(s): We used clinical samples and cultured trophoblast cells to evaluate syncytial integrity of placentas exposed to SARS-CoV- 2. Autophagic flux was measured in placental villous biopsies from SARS-CoV-2-exposed and unexposed pregnant women by quantifying the expression of autophagy markers, LC3 and P62. Trophoblast cells (JEG-3, Forskolin-treated JEG-3, HTR8/SVneo, or primary human trophoblasts (PHTs)) were transfected with expression plasmids encoding SARS-CoV-2 proteins including ORF3a. Using western blotting, multi-label immunofluorescence, and confocal imaging, we analyzed the effect of ORF3a on the autophagy, differentiation, invasion, and intracellular trafficking of ZO-1 in trophoblasts. Using coimmunoprecipitation assays, we tested ORF3a interactions with host proteins. t-tests and one-way analyses of variance (ANOVAs) with post hoc tests were used to assess the data, with significance set at P < .05. Result(s): We discovered :1) increased activation of autophagy, but incomplete processing of autophagosome-lysosomal degradation;2) accumulation of protein aggregates in placentas exposed to SARS-CoV- 2. Mechanistically, we showed that the SARS-CoV-2 ORF3a protein, uniquely 3) blocks the autophagy-lysosomal degradation process;4) inhibits maturation of cytotrophoblasts into syncytiotrophoblasts (STBs);5) reduces production ofHCG-beta, a key pregnancy hormone that is also essential for STB maturation;and 6) inhibits trophoblast invasive capacity. Furthermore, ORF3a harbors an intrinsically disordered C-terminus withPDZ-bindingmotifs.We show for the first time that, 7) ORF3a binds to and co-localizes with the PDZ domain of ZO-1, a junctional protein that is essential for STB maturation and the integrity of the placental barrier. Conclusion(s): Our work outlines a new molecular and cellular mechanism involving the SARS-CoV-2 accessory protein ORF3a that may drive the virus's ability to infect the placenta and damage placental syncytial integrity. This implies that the mechanisms facilitating viral maturation, such as the interaction of ORF3a with host factors, can be investigated for additional functionality and even targeted for developing new intervention strategies for treatment or prevention of SARS-CoV-2 infection at the maternal-fetal interface.

Disparities in COVID-19 Related Outcomes in the United States By Race and Ethnicity: An Umbrella Review of Meta-Analyses

Objectives: Meta-analyses have investigated associations between race and ethnicity and COVID-19 outcomes. However, there is uncertainty about these associations' existence, magnitude, and level of evidence. We, therefore, aimed to synthesize, quantify, and grade the strength of evidence of race and ethnicity and COVID-19 outcomes in the US. Method(s): In this umbrella review, we searched four databases (Pubmed, Embase, the Cochrane Database of Systematic Reviews, and Epistemonikos) from database inception to April 2022. The methodological quality of each meta-analysis was assessed using the Assessment of Multiple Systematic Reviews, version 2 (AMSTAR-2). The strength of evidence of the associations between race and ethnicity with outcomes was ranked according to established criteria as convincing, highly suggestive, suggestive, weak, or non-significant. The study protocol was registered with PROSPERO, CRD42022336805 Results: Of 880 records screened, we selected seven meta-analyses for evidence synthesis, with 42 associations examined. Overall, 10 of 42 associations were statistically significant (p <= 0.05). Two associations were highly suggestive, two were suggestive, and two were weak, whereas the remaining 32 associations were non-significant. The risk of COVID-19 infection was higher in Black individuals compared to White individuals (risk ratio, 2.08, 95% Confidence Interval (CI), 1.60-2.71), which was supported by highly suggestive evidence;with the conservative estimates from the sensitivity analyses, this association remained suggestive. Among those infected with COVID-19, Hispanic individuals had a higher risk of COVID-19 hospitalization than non-Hispanic White individuals (odds ratio, 2.08, 95% CI, 1.60-2.70) with highly suggestive evidence which remained after sensitivity analyses. Conclusion(s): Individuals of Black and Hispanic groups had a higher risk of COVID-19 infection and hospitalization. These associations of race and ethnicity and COVID-19 outcomes existed more obviously in the pre-hospitalization stage. More consideration should be given in this stage for addressing health inequity.Copyright © 2023

Re-setting special education for justice: An essay on the logics and infrastructure enabling deep change in the COVID-19-era

COVID-19 shocked the education system, disrupting the policies and practices of special education over multiple school years. This essay brings together the institutional logics perspective and racialized organization theory to first examine aspects of special education and then describe how leaders and teachers can improve special education to target inequities. We illustrate features of three logics of special education: compliance, intervention, and equity. We explain how these logics are racialized structures in the special education field. Applying an agentic stance, we portray how leaders and teachers draw on multiple, competing logics of special education. Next, we highlight how infrastructure enables leaders and teachers to enact the equity model of special education. In sum, this essay encourages improving infrastructural elements and confronting racism and ableism to re-envision special education in the face of COVID-disruptions.

Understanding First Contact Physiotherapists Experiences of Remote Consultations in Primary Care

Background/Aims First Contact Physiotherapists (FCPs) assess, diagnose and manage patients presenting with musculoskeletal disorders in primary care, without the need for prior GP consultation. Prior to COVID-19 almost every consultation was conducted in-person. Since the pandemic, many consultations are now undertaken remotely, a trend that is set to continue in line with the 'Digital first' strategy which seeks to enhance patient access to appointments. This aim of this study was to explore FCP views of remote consultations and how this impacted their role satisfaction and wellbeing. Methods This mixed methods two phase study consisted of an online survey investigating distributed via professional networks and through social media. The phase one survey explored consultation methods;levels of training;challenges and benefits;and a stress appraisal. Data were analysed descriptively. Respondents were invited to take part in phase two which included a semi-structured interview to gain an in-depth understanding of FCPs lived experience of remote consultation ways of working. Transcripts were thematically analysed. Results The online survey received n=109 responses from UK-based FCPs. Data revealed that despite the 'Digital First' push for continued remote consultations, the majority of FCPs (62%) used them for less than a quarter of their appointment slots. Whilst recognising that many patients found this format convenient, FCPs highlighted their own stress levels, citing poor efficacy, anxiety of misdiagnosis, feelings of isolation and increased administrative workload. Nearly two thirds (66%) of respondents had not received any training in how to conduct effective remote consultations. Follow-up interviews with n=16 FCPs highlighted coping strategies including following up with an in-person consultation and directing patients to other community health and wellbeing resources. In areas of high socioeconomic deprivation and poor health literacy additional problems associated with communication difficulties, poor IT access and capability, and digital poverty were all cited. Conclusion Remote consultations may offer a convenient alternative for some patients. FCP responses suggest that the continued offer of remote consultation is decreasing now pandemic restrictions have been lifted, despite the push for continued digital working practices. The perceived lack of efficacy, and fear of missing important diagnostic information means that many FCPs are either returning to in-person consultation or following up with a second face-to-face assessment resulting in potential service inefficiencies. Additional challenges were identified in areas of high deprivation and low health literacy, and the value of this consultation format needs to be considered in this context. Future work should focus on the training and support needs of FCP staff who are engaging with remote working to ensure clinical effectiveness and staff wellbeing.

Racial Disparities in Elective Total Knee and Hip Replacement Surgeries during the Covid-19 Pandemic: A Retrospective Study of a Diverse Population in Washington State

Purpose of Study: Total knee (TKA) and hip (THA) arthroplasty procedures are recognized as effective treatments for osteoarthritis of the knee and hip joints which are the leading causes of lower extremity disability among older adults. Previous studies have demonstrated a variance in patients electing to undergo these interventions with non-White patients having significantly lower utilization rates. Our study examined if these disparities continued to exist during the COVID-19 pandemic period. Methods Used: This retrospective cohort study included 580 patients who underwent TKA or THA in 2020 and 2021 in a racially diverse region in Washington State. Demographic data, comorbidities, and post-surgical outcomes were recorded. Patients were stratified as those identifying as White (n=490, 84.5%) or Hispanic/ Latino (n=65, 11.2%). Patients identifying with other races (n=25, 4.3%) were excluded from the study due to small sample sizes. Differences between our two groups were examined using a chi-square test for categorical variables and an independent t-test for continuous variables. The level of significance was set at P < 0.05. Summary of Results: Compared to the White patients, Hispanic/ Latino identifying patients were younger (61.9+/-12.79 years versus 68.58+/-9.00 years;P <0.001), had lower Charlson Comorbidity Index scores (P=0.019), and were more likely to use non-Medicare or Medicaid insurance (P <0.001). No differences were observed in postoperative complication (P=0.632) and COVID-19 infection (P=0.465) rates between the groups. Conclusion(s): Although Hispanic/ Latino identifying patients in this region constitute 45.8% of our study population according to the most recent census tabulation, they accounted for only 11.2% of the patients in our study. These patients were also younger, had fewer comorbidities, and tended to use non-Medicare or Medicaid insurance suggesting an exclusive Hispanic/ Latino patient population electing to undergo TKA or THA procedures during the COVID-19 pandemic. Future studies controlling for osteoarthritis risk factors and patients' election of treatment options may explain these disparities we have observed.

A fast point-of-care PCR test for infectious diseases, based on aerosol capturing

The COVID-19 pandemic quickly revealed the limitations of existing monitoring and diagnostic capabilities. While rapid antigen tests are not sufficiently reliable, PCR turn-around-time (TAT) typically ranges from hours to days. Standard swab-based tests are also cumbersome and invasive and, worse yet, they detect infection and not transmissibility. A reliable diagnostic test able to discern the infectious phase of COVID-19 could interrupt transmission while limiting isolation requirements. We developed a non-invasive, impaction-based method for capturing aerosols from human breath in one minute of sampling. A proof-of-principle system was used for the detection of viral RNA in breath samples from confirmed positive subjects (=29). A lab setup demonstrated compatibility with on-chip PCR, reducing the TAT to 15-20 minutes. Positive percentage agreement (PPA) between a breath- and nasopharyngeal PCR is 75% overall and 92% in the first 7 days of infection, after which the breath does not contain measurable virus anymore. Breath positivity corresponds to the infectious window. No false positives were noted. Diagnostic accuracy is superior to nasopharyngeal rapid antigen tests. This novel concept of aerosol capturing combined with ultra-fast PCR is proven to be effective to detect SARS-CoV-2 in breath, rivalling the standard nasopharyngeal PCR tests. Combined with a TAT on par with rapid antigen tests, the technology has the potential to become a standard test in the coming years, for COVID-19 or other infectious diseases. A validation study with an advanced setup is currently ongoing, first data should be available during the presentation.

Early Clinical Development of Lufotrelvir as a Potential Therapy for COVID-19

Lufotrelvir was designed as a first in class 3CL protease inhibitor to treat COVID-19. Development of lufotrelvir was challenged by its relatively poor stability due to its propensity to epimerize and degrade. Key elements of process development included improvement of the supply routes to the indole and lactam fragments, a Claisen addition to homologate the lactam, and a subsequent phosphorylation reaction to prepare the prodrug as well as identification of a DMSO solvated form of lufotrelvir to enable long-term storage. As a new approach to preparing the indole fragment, a Cu-catalyzed C-O coupling using oxalamide ligands was demonstrated. The control of process-related impurities was essential to accommodate the parenteral formulation. Isolation of an MEK solvate followed by the DMSO solvate ensured that all impurities were controlled appropriately. © 2023 American Chemical Society.

Utility of Continuous Positive Airway Pressure (CPAP) in COVID pneumonitis patients not suitable for mechanical ventilation

Hospitals throughout the country have utilised different strategies in the management of COVID pneumonitis. Our hospital established a Respiratory High Care Unit (RHCU) to provide CPAP to patients deteriorating despite Standard Oxygen Therapy (SOT). Patients were considered to be either for full escalation (intubation and mechanical ventilation) or to have CPAP as a ceiling of care. Our aim was to assess CPAP success in those not eligible for mechanical ventilation. We retrospectively analysed patients admitted to RHCU who had a CPAP ceiling of care. Between 1st June 2020 and 31st March 2021, 156 patients were admitted, with 144 notes available for analysis. Patients were transferred to RHCU following review by respiratory consultant and met Trust criteria for CPAP. 75 patients (52%) had a ceiling of care of CPAP. 8 patients were excluded. Average age was 75.1 years. Mean Clinical Frailty Score (CFS) was 3.6. 70% were male. 97% were admitted with FiO2 >=40%. Mortality in patients with CPAP as ceiling of care was 79%. Patients that survived had a mean age was 74.6 years, a mean CFS of 3.1 and a pO2 on admission of 7.8kPa, as compared to a mean age of 75.2 years, a mean CFS of 3.7 and pO2 on admission of 7.7kPa in those that died. Demographics between the two cohorts of patients were similar, making it difficult to predict who would survive with CPAP therapy. 21% of patients not suitable for mechanical ventilation survived with CPAP. In other centres, these patients may have only been eligible for SOT alone. The data suggests that offering CPAP may increase survival in patients that would not be suitable for mechanical ventilation.

Partnering with primary care to implement evidence based interventions (EBI) to address overdue colorectal cancer (CRC) screening in Connecticut (CT)

PURPOSE: Partnering with the largest Federally Qualified Health Center (FQHC) in New Haven, CT, the goal is to implement and test 4 evidence-based interventions (EBI) to increase CRC screening, while evaluating real-world implementation. Here, we report on the six-month (approximate) follow up of a cohort of 3,127 patients overdue for CRC screening who received 1 or more EBIs in October 2021. BACKGROUND: Sociocultural and medical concerns are barriers to colonoscopy uptake contributing to disparities in CRC screening. An additional barrier is system level capacity. COVID-19 associated delays exacerbated the existing backlog of individuals overdue for CRC screening, underscoring the need to expand Fecal Immunochemical Testing (FIT) capacity. This was particularly evident in the safety-net primary care setting that serves lower socio-economic status individuals living in urban New Haven, CT. METHOD(S): We are testing the unique and additive value of multiple evidence-based interventions (EBIs) for increasing CRC screening. The EBIs include the use of medical reminders, addressing the structural barriers (social determinants of health [SDOH]), and providing assistance from community health workers (CHW). We randomized 3,127 patients overdue for CRC screening to one of 4 arms of the study. All individuals received a reminder from their providers that they were due/overdue for CRC screening with instructions to contact the FQHC. Arm 2 also included information on SDOH barriers, Arm 3 included this same information with offer of navigation from CHW/navigator;and Arm 4 included the offer of CHW educational video and support if needed. Six-month (approximate) outcomes include: 1) Engagement with FQHC resulting in ordered test;2) completed test. Results by intervention will be assessed at 12 months. RESULT(S): Of the 3,127 randomized patients, ages 50-75, 77% were Hispanic (33%) or Black (44%). At 6+ months, a preliminary look at EMR data show that a minimum of 1,275 (40.8%) patients "engaged" with providers resulting in an ordered FIT Kit (n= 1174) or COMPLETED screening colonoscopy that was not associated with a positive FIT result (n = 102). 217 (18.5%) individuals completed the FIT testing with 13 requiring confirmatory colonoscopy (31% completed at this time). Thus, a minimum of 319 (10%) of 3,127 individuals in the cohort completed CRC screening at approximately 6 months post intervention. DISCUSSION: Despite investments in community engagement, stakeholder input, and FIT kit capacity building, the pandemic presented unforeseen challenges. Flexibility and steadfast commitment from FQHC providers and staff were critical to successful implementation during multiple waves of COVID-19, resulting in CRC screening ordered for 41% of cohort within 6 months of intervention. SUMMARY: At 6 months follow up of 3,127 individual who were overdue for CRC screening, one or more of 4 EBIs, in addition to system level efforts to address CRC screening, resulted CRC screening tests ordered for 41% of cohort with at least 10% completed screening.

Virtual screening for uveal melanoma: A Princess Margaret cancer centre perspective during the COVID-19 pandemic

Princess Margaret Cancer Centre (PM) receives roughly 120 new patients (pts) per year with uveal melanoma (UM). Moderate to high-risk pts, based on AJCC staging and cytogenetics, undergo a strict surveillance program for metastases with liver MRI every 4-6 months and annual chest imaging. The importance of surveillance has been highlighted by new therapies which are likely more effective in pts with lower volume metastases. In this single center retrospective study, we assessed the effectiveness of a virtual surveillance model, by comparing UM pts on standard in-person surveillance (SS) pre-COVID (August 2018 to March 2020) with virtual surveillance (VS) after COVID onset (April 2020 to November 2021). Virtual visits were done through phone or MS Teams video calls, and images were done either locally or externally. We identified 106 pts who underwent SS and 107 pts who underwent VS. In the SS group, 10 pts were diagnosed with metastasis and of these 9 (90%) were staged as M1a disease and 1 (10%) was M1b. In the VS group, 20 pts were diagnosed with metastases, 2 (10%) of which had M1b disease and 18 (90%) with M1a disease. Fifteen (14%) pts in the SS group and 34 (20%) pts in the VS group lived out of province;13 (12%) of the SS pts and 36 (21%) of pts in the VS cohort had scans externally. With regards to surveillance adherence in the SS group, 70 (66%) of pts had their scans performed on time versus 127 (75%) of pts in the VS cohort. Virtual screening of pts with moderate to high-risk UM during the COVID 19 pandemic showed similar ability to detect low volume disease compared with our standard screening. There was a higher level of adherence to screening during the VS period. When implemented appropriately, VS appears to be an effective model to monitor UM pts.

Impacts of the Early COVID-19 Pandemic on the Work of Bioethicists in Canada

Bioethics experts played a key role in ensuring a coherent ethical response to the COVID-19 pandemic in the fields of healthcare, public health, and scientific research in Canada. In the province of Quebec, a group of academic and practicing bioethicists met periodically in the early months of the pandemic to discuss approaches and solutions to ethical dilemmas encountered during the crisis. These meetings created the opportunity for a national survey of bioethics practitioners from different fields. The survey, in which forty-five Canadian bioethics practitioners (clinical ethicists, ethicist members of REBs and government health policy ethicists, or any bioethicist practicing outside of academia) participated, explored their concerns, challenges and opportunities during the first wave of the pandemic, with the objective of informing bioethics research about the difficulties experienced by bioethicists "in the field". Participants reported increased stress levels, increased workloads, and a greater proportion of their work being devoted to public health ethics. Most of their concerns focused on groups other than themselves, such as health professionals, patients, research participants, and people in vulnerable socio-economic situations. An optimism about the future of bioethics was noted due to an increased awareness of the importance of bioethics by the public and by health and research institutions.

SARS-CoV-2 Illness Severity and Early Hospitalization Outcomes in a Multicenter Prospective Cohort Study Among Veterans

Background. Over 600,000 SARS-CoV-2 infections and 20,000 deaths have occurred among users of the Veterans Health Administration, the US's largest integrated health care system. We explored early outcomes of SARS-COV-2 infection in Veterans. Methods. An ongoing, prospective longitudinal cohort study of Veterans ages >= 18 enrolled 1,826 participants (29.0% inpatient;49.1% vaccinated;68.3% SARS-CoV-2-positive;85.0% male, mean age = 57.1 years) seeking inpatient or outpatient care after SARS-CoV-2 testing at 15 Department of Veterans Affairs medical centers in July 2020 to February 13, 2022. Using multivariable regression, we estimated relationships of baseline demographic characteristics, COVID-19 vaccination, and clinical history to illness severity and cumulative length of hospital stay within 60 days of study entry. Illness severity was defined by a Veterans Affairs adaptation of the WHO COVID-19 severity scale and included 4 levels (mild, moderate, severe, or death). We derived the Charlson co-morbidity index (CCI) and other baseline characteristics from electronic health data and study questionnaires, and reported qualitative SARS-CoV-2 IgG responses using inpatients' study-collected blood specimens. Results. High CCI scores (>= 5) occurred in 47 (42.7%) vaccinated SARS-CoV-2-positive inpatients and 47 (21.2%) unvaccinated. Severe illness occurred in 17 (15.5%) vaccinated inpatients, 37 (16.7%) unvaccinated inpatients, 4 (0.9%) vaccinated outpatients, and 3 (0.7%) unvaccinated outpatients. Eleven (10%) of 110 vaccinated SARS-CoV-2-positive inpatients died, as did 15 (6.8%) of the 222 unvaccinated. In SARS-CoV-2-positive inpatients, a one-step higher CCI was associated with more severe illness (aOR 1.10, 95%CI 1.01-1.20) and more hospitalization days (aIRR 1.06, 95% CI 1.03-1.10), adjusting for vaccination status. Respectively, 93% of vaccinated and 63% of unvaccinated SARS-CoV-2 positive inpatients with baseline antibody results had an anti-spike IgG response. Conclusion. In an ongoing longitudinal cohort study of COVID-19 in US Veterans, comorbidity burden was higher among vaccinated than unvaccinated inpatients and was associated with more severe illness and hospitalization days, independent of vaccination status.

Bacterial co-infection in COVID-19: an analysis of a National Cohort of Hospitalized U.S. Veterans

Background. Bacterial co-infection has been reported with COVID-19, but the extent of co-infection nationally is unclear. We sought to describe the temporal and spatial trends in bacterial co-infection across the US among COVID-19 positive admissions to Veterans Affairs (VA) hospitals. Methods. This retrospective cohort study included patients admitted to VA hospitals from March 1, 2020 through May 31, 2022 with a positive COVID-19 test within the previous 14 days and up to 2 days after admission. We summarized temporal and spatial patterns of bacterial co-infection, defined as a positive clinical microbiology culture for the bacterial pathogens listed in Table 1, defined as either community-onset (COI, within 2 calendar days of admission), or hospital-onset (HOI, > 2 calendar days after admission). We performed a univariate analysis including facility and patient factors and generated descriptive statistics to describe the frequency of occurrence over time and space overall, and within each organism. Results. By the end of June 2021, there were 35,299 hospitalizations observed from 33,383 patients admitted with positive COVID-19 tests in VA. Co-infection was detected among 7.4% of hospitalizations (2.9% for COI and 4.7% for HOI). VA patients older than 70, Asian or unknown race, higher Charlson Comorbidity Index were more likely to experience HOI and COI. Facility-level rates of HOI and COI over the study period presented substantial geographic variability, ranging from 0 to 45.5 per 1000 patient days and from 0 to 6.98 per 100 hospitalizations for HOI and COI, respectively [Fig 1]. Between March 2020 and June 2021, monthly facilitylevel rates of HOI and COI also varied substantially within and between facilities [Fig 2]. Average monthly co-infection rates increased in the first three months of the pandemic, with HOIs subsequently declining gradually and COIs remaining stable across VA. The correlation coefficients between hospital mortality and facility-level coinfection rates for HOI and COI ranged from -0.5 to 0.7 [Fig 3]. Conclusion. Bacterial co-infection was infrequent during hospitalization with COVID-19 in the VAhealthcare system, and has mild tomoderate association with hospital mortality. However, substantial geographic and temporal variation was observed.

Predictors of Co-infection with Multidrug Resistant Organisms among Hospitalized Patients with COVID-19: An Exploratory Analysis

Background. Bacterial co-infection has been reported with COVID-19, but risk factors for bacterial co-infection remain unclear due to limited large scale studies. We seek to identify predictive factors associated with risk of co-infection with multidrug-resistant organisms for patients hospitalized at Veterans Affairs (VA) hospitals with COVID-19. Methods. This retrospective cohort study included Veterans admitted to VA hospitals from March 1, 2020 through May 31, 2022 with a confirmed positive COVID-19 test within the previous 14 days and up to 2 days after admission. Outcomes of interest were hospital-onset co-infection (HOI, > 2 calendar days after admission) and community-onset co-infection (COI, within 2 calendar days of admission). Potential risk factors included both patient- (e.g. vital sign, medication use) and facility-level covariates (e.g. bed size, antibiotic use rate). We compared the covariate distributions for patients with and without HOI and COI. Our analytical approaches included variance inflation factors to detect the presence of multicollinearity among these factors, and Least Absolute Shrinkage and Selection Operator to identify the subset of factors associated with HOI and COI. We conducted a two-stage analysis, first performing feature selection among the individual-level risk factors followed by identification of facility-level risk factors. Optimal models were identified using 10-fold cross validation. Results. By July 2021, 33,383 patients were admitted to VA with positive COVID-19 test. We found that medications for ventilator induction (OR with 95% CI: 2.9 (2.2, 3.9)), norepinephrine (OR with 95% CI: 1.6 (1.2, 2.2)) and antimicrobial therapies for gram-positive infections (OR with 95% CI: 4.5 (3.6, 5.6)) [Table 1] were associated with the increased risk of HOI and patients in facilities with high C difficile infection rates were more likely to have COI detected (OR with 95% CI: 1.14 (1.11, 1.18)) [Table 2]. Homeless Veterans had higher risk of developing an HOI (OR with 95% CI: 1.5 (1.1, 2.0)), but not a COI. Conclusion. Risk factors for HOI and COI in COVID-19 were distinct, with specific classes of medications and antibiotics as well as patient factors resulting in increased risk for HOI. Further work is needed to better understand the risk factors for COI. (Table Presented).

“Is the focus in professional rugby ever really on health?”: A qualitative study on the uptake of illness prevention guidelines in rugby

Illness prevention is essential for athlete health management, but little is known about its uptake in sport. Prior to the pandemic, the International Olympic Committee (IOC) published a consensus statement recommending illness prevention guidelines are implemented in sports. Yet, little is known about guideline uptake. Therefore, this study aimed to explore the (1) illness experiences of rugby players and athlete support personnel and (2) barriers and enablers to illness prevention guideline uptake in rugby, using the lens of behaviour change theory. In a bid to inform and enhance athlete welfare, we sought to amplify the voices of participants through qualitative inquiry. Between August 2020 and May 2021, 16 semi-structured interviews were undertaken with players and athlete support personnel working across rugby. Analysis was conducted using Braun and Clarke's reflexive thematic analysis. Prior to COVID-19, participants deemed illness to be of little concern, with experience of illnesses and the global pandemic critical enablers to guideline uptake. The rugby environment was a barrier to illness prevention, particularly in women's and academy teams where resource deficiency was highlighted. ‘Rugby identity’ acted as both a barrier and enabler with participants’ passion for rugby driving both guideline adherence and non-adherence. Tackling resource inequalities between men's and women's cohorts is critical to effectively implement guidelines. Coach and player education is essential, and emphasis must be placed on continuing preventative behaviours adopted due to COVID-19. Our findings offer new insight into illness prevention, moving away from prevailing quantitative research, and instead voicing players’ experiences. © 2022 Elsevier Ltd

Utility of continuous positive airway pressure (CPAP) in COVID pneumonitis patients not suitable for mechanical ventilation

Hospitals throughout the country have utilised different strategies in the management of COVID pneumonitis. Our hospital established a Respiratory High Care Unit (RHCU) to provide CPAP to patients deteriorating despite Standard Oxygen Therapy (SOT). Patients were considered to be either for full escalation (intubation and mechanical ventilation) or to have CPAP as a ceiling of care.Our aim was to assess CPAP success in those not eligible for mechanical ventilation.We retrospectively analysed patients admitted to RHCU who had a CPAP ceiling of care. Between 1stJune 2020 and 31st March 2021, 156 patients were admitted, with 144 notes available for analysis. Patients were transferred to RHCU following review by respiratory consultant and met Trust criteria for CPAP. 75 patients (52%) had a ceiling of care of CPAP. 8 patients were excluded.Average age was 75.1 years. Mean Clinical Frailty Score (CFS) was 3.6. 70% were male. 97% were admitted with FiO2 ≥40%. Mortality in patients with CPAP as ceiling of care was 79%.Patients that survived had a mean age was 74.6 years, a mean CFS of 3.1 and a pO2 on admission of 7.8kPa, as compared to a mean age of 75.2 years, a mean CFS of 3.7 and pO2 on admission of 7.7kPa in those that died. Demographics between the two cohorts of patients were similar, making it difficult to predict who would survive with CPAP therapy.21% of patients not suitable for mechanical ventilation survived with CPAP. In other centres, these patients may have only been eligible for SOT alone. The data suggests that offering CPAP may increase survival in patients that would not be suitable for mechanical ventilation.

Assessing burnout and mental health of respiratory high care unit (RHCU) staff two years into the Covid-19 pandemic

During the pandemic, our hospital established a RHCU to provide level 2 care for patients with severe Covid-19. Mortality rate was 54% over the first year. We designed a questionnaire around Patient Health Questionnaire-9 to assess the emotional impact upon our workforce. We also evaluated burnout, using the Oldenburg Burnout Inventory.Staff retrospectively rated their pre-pandemic mental health (Feb 2020) and current mental health (Jan 2022). 60 questionnaires were circulated with 83% completed.Doctors encompassed 28% of respondents, nurses 38%, HCAs 18%, and 16% were other clinical and administrative staff. 62% had worked on RHCU for ≥12 months.72% felt their mental health had deteriorated. 94% reported their physical health had been negatively impacted.In Jan 2022, 51% reported feeling depressed, 71% anxious, 46% tearful and 69% irritable, half the time or more. All figures had increased ≥2 fold compared to pre-pandemic levels.The pandemic has affected personal life too, showing a 3.6 fold increase in strain on personal relationships compared to pre-pandemic. 70% reported difficulty with sleep pattern.Worryingly, 71% scored high/very high using the Oldenburg Burnout Inventory. Levels of burnout were notably increased in junior doctors (88%) and staff nurses (89%), demonstrating high/very high levels of burnout. 75% of junior doctors and 56% of staff nurses were unsure or would not continue in their current role. These figures are incredibly concerning, considering that junior doctors and staff nurses make up one third of RHCU staff.Our results highlight the need for urgent intervention for RHCU staff to prevent further burnout and improve mental health.

Utility of Continuous Positive Airway Pressure (CPAP) in avoiding mechanical ventilation in COVID-19 patients

There has been much debate on how best to manage COVID pneumonitis. We established a Respiratory High Care Unit (RHCU) to provide CPAP for hypoxic patients as an intermediate between standard oxygen therapy (SOT) and mechanical ventilation (MV). In some centres, CPAP was not offered outside trial settings, meaning deteriorating patients went straight from SOT to MV.The RECOVERY-RS trial has found that CPAP reduces the need for MV in severe COVID. This study reported for every 12 people treated with CPAP, in comparison to SOT, 1 patient avoided MV.1Between 1/6/20 and 30/3/21, we admitted 156 patients to the RHCU. All patients met local Trust criteria for CPAP. Out of these, 69 patients (48%) were considered to be suitable for full escalation (intubation and mechanical ventilation on ITU). 1 patient died of non-COVID causes and was excluded. Of the remaining 68 patients, 72% improved with CPAP, with all patients surviving until discharge. 28% were transferred to intensive care for MV.Patients that avoided intubation had a mean age of 53.8 years, an average clinical frailty score (CFS) of 1.3 and a pO2 on admission to RHCU of 9.1kPa versus an age of 63.5 years, CFS of 1.5 and pO2 of 8.0kPa in those intubated.This analysis showed that CPAP was an effective modality of treatment, with 72% of patients avoiding going on to MV, which was the standard care provided in some other centres. For every 1.4 patients given CPAP, 1 MV was avoided. This data strongly supports emerging evidence on the benefit of CPAP in avoiding MV in COVID patients.Perkins G, Ji C, Connolly B, Couper K, Lall R, Baillie J et al. An adaptive randomized controlled trial of non-invasive respiratory strategies in acute respiratory failure patients with COVID-19. 2021.

Supplemental Instruction to Decrease Equity Gaps in GateKeeper Engineering Courses (ERM)

This study explores the impact of Technology-Assisted Supplemental Instruction (TASI) on the sense of belonging and academic achievement of URM identified students in Statics courses at a large public HSI university. TASI is a peer-led tutoring service in partnership with faculty support that targets high failure rate STEM courses, in this case, three different iterations of Statics. Students completed four surveys that measured demographics, sense of belonging in their field of study, and confidence in their ability to do well in their courses. In addition, TASI attendance, students' academic and enrollment data were collected. Preliminary belonging data at the beginning of the term showed the nearly 80% of Latinx students agreed with the statements: “I sometimes feel like other students in my field of study have skills that I do not,” and “When I struggle in a class I feel that I don't belong in the field”. Linear regression also shows that the main predictor of student grades in Statics are identifying as a URM student or Pell recipient. TASI has the goal of increasing academic support and therefore performance to alleviate these feelings and ensure student persistence. Using matched pairs analysis, the data shows a statistically significant increase of 0.4 to 0.5 in course grade on a 4-point scale. These results were most apparent in URM students. The rate of failing grades for URM students decreased up to twenty percent (depending on the section). The impact of the TASI is more evident for students of color during the COVID pandemic and virtual learning. The use of an anti-deficit lens highlights how imperative it is to have meaningful, useful, and accessible interventions. Student facilitators, access, and awareness of programs are noted as crucial to success. © American Society for Engineering Education, 2022.