Substantial reduction in the clinical and economic burden of disease following variant-adapted mRNA COVID-19 vaccines in immunocompromised patients in France (preprint)

An economic evaluation was conducted to predict the economic and clinical burden of vaccinating immunocompromised (IC) individuals aged ≥30 years with mRNA-1273 variant-adapted COVID-19 vaccines in Fall 2023 and Spring 2024 versus BNT162b2 variant-adapted vaccines in France. The number of symptomatic COVID-19 infections, hospitalizations, deaths, and long COVID cases, costs and quality-adjusted life years (QALYs) was estimated using a static decision-analytic model. Predicted vaccine effectiveness (VE) were based on real-world data from prior versions, suggesting higher protection against infection and hospitalization with mRNA-1273 vaccines. VE estimates were combined with COVID-19 incidence and probability of COVID-19 severe outcomes. Uncertainty surrounding VE, vaccine coverage, infection incidence, hospitalization and mortality rates, costs and QALYs were tested in sensitivity analyses. The mRNA-1273 variant-adapted vaccine is predicted to prevent an additional 3,882 infections, 357 hospitalizations, 81 deaths, and 326 long COVID cases when compared to BNT162b2 variant-adapted vaccines in 230,000 IC individuals. This translates to €10.1 million cost-savings from a societal perspective and 645 QALYs saved. Results were consistent across all analyses and most sensitive to variations surrounding VE and coverage. These findings highlight the importance of increasing vaccine coverage, and ability to induce higher levels of protection with mRNA-1273 formulations in this vulnerable population.

The potential economic impact of the updated COVID-19 mRNA fall 2023 vaccines in Japan (preprint)

This analysis estimates the economic and clinical impact of a Moderna updated COVID-19 mRNA Fall 2023 vaccine for adults at least 18 years in Japan. A previously developed Susceptible Exposed Infected Recovered (SEIR) model with a 1 year analytic time horizon (September 2023 to August 2024) and consequences decision tree were used to estimate symptomatic infections, COVID19 related hospitalizations, deaths, quality adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) for a Moderna updated Fall 2023 vaccine versus no additional vaccination, and versus a Pfizer-BioNTech updated mRNA Fall 2023 vaccine. The Moderna vaccine is predicted to prevent 7.2 million symptomatic infections, 272,100 hospitalizations and 25,600 COVID-19 related deaths versus no vaccine. In the base case (healthcare perspective), the ICER was 1,300,000 Yen/QALY gained ($9,400 USD/QALY gained). Sensitivity analyses suggest results are most affected by COVID 19 incidence, initial vaccine effectiveness (VE), and VE waning against infection. Assuming the relative VE between both bivalent vaccines apply to updated Fall 2023 vaccines, the base case suggests the Moderna version will prevent an additional 1,100,000 symptomatic infections, 27,100 hospitalizations, and 2,600 deaths compared to the Pfizer-BioNTech vaccine. The updated Moderna vaccine is expected to be highly cost effective at a 5 million Yen willingness to pay threshold across a wide range of scenarios.

Clinical and Economic impact of updated Fall 2023 COVID-19 vaccines in the Immunocompromised Population in Canada (preprint)

Background Immunocompromised (IC) individuals are at increased risk of COVID-19 infection-related severe outcomes. Moderna and Pfizer-BioNTech COVID-19 mRNA vaccines are available in Canada, and differences in vaccine effectiveness (VE) have been found between the two in IC individuals. The objective of this analysis was to compare the clinical and economic impact of a Moderna XBB.1.5 updated COVID-19 mRNA Fall 2023 vaccine to a Pfizer-BioNTech XBB.1.5 updated COVID-19 mRNA Fall 2023 vaccine in Canadian IC individuals aged [≥]18 years. MethodsA static decision-analytic model estimated the number of COVID-19 infections, hospitalizations, deaths, and resulting quality-adjusted life years (QALYs) over a one-year time horizon (September 2023-August 2024) in the Canadian IC adult population (n=894,580). Costs associated with COVID-19 infection were estimated from health care and societal perspectives. The predicted VE of the updated Moderna vaccine was based on prior variant versions, which were well-matched to the circulating variant. Pfizer-BioNTech VE was calculated based on a meta-analysis of comparative effectiveness between both vaccines (relative risk for Moderna vaccine: infection=0.85 [95%CI 0.75-0.97], hospitalization=0.88 [95%CI 0.79-0.97]). The model combined VE estimates with COVID-19 incidence and probability of COVID-19 related severe outcomes. Sensitivity analyses tested the impact of uncertainty surrounding incidence, hospitalization and mortality rates, costs, and QALYs. ResultsGiven the expected higher VE against infection and hospitalizations with the Moderna Fall 2023 vaccine, its use is predicted to prevent an additional 2,411 infections (3.6%), 275 hospitalizations (3.7%), and 47 deaths (4.0%) compared to the Pfizer-BioNTech Fall 2023 vaccine, resulting in 330 QALYs gained, and savings of $7.4M in infection treatment costs, and $0.9M in productivity loss costs. Results were most sensitive to variations in VE parameters, specifically the relative risk of infection and hospitalizations between the vaccines, and waning rates. ConclusionsIf the Moderna and Pfizer-BioNTech Fall 2023 vaccines protect against infection and hospitalizations similar to previous vaccines, using the Moderna Fall 2023 vaccine would result in substantial public health benefits in IC individuals, as well as provide health care and societal cost savings.

ChineseCVD: first-in-world, web-based, Chinese-specific Cardiovascular Risk Calculator incorporating long COVID, COVID-19 vaccination, SGLT2i and PCSK9i treatment effects (preprint)

BackgroundWeb-based risk prediction tools for cardiovascular diseases are crucial for providing rapid risk estimates for busy clinicians, but there is none available specifically for Chinese subjects. This study developed ChineseCVD, first-in-world web-based Chinese-specific Cardiovascular Risk Calculator incorporating long COVID, COVID-19 vaccination, SGLT2i and PCSK9i treatment effects. MethodsAdult patients attending government-funded family medicine clinics in Hong Kong between 1st January 2000 and 31st December 2003 were included. The primary outcome was major adverse cardiovascular events (MACE) defined as a composite of myocardial infarction, heart failure, transient ischaemic attacks/ischaemic strokes, and cardiovascular mortality. ResultsA total of 155,066 patients were used as the derivation cohort. Over a median follow-up of 16.1 (11.6-17.8) years, 31,061 (20.44%) had MACE. Cox regression identified male gender, age, comorbidities, cardiovascular medications, systolic and diastolic blood pressure, and laboratory test results (neutrophil-lymphocyte ratio, creatinine, ALP, AST, ALT, HbA1c, fasting glucose, triglyceride, LDL and HDL) as significant predictors of the above outcomes. ChineseCVD further incorporates the impact of smoking status, COVID-19 infection, number of COVID-19 vaccination doses, and modifier effects of newest medication classes of PCSK9i and SGLT2i. The calculator enables clinicians to demonstrate to patients how risks vary with different medications. ConclusionsThe ChineseCVD risk calculator enables rapid web-based risk assessment for adverse cardiovascular outcomes, thereby facilitating clinical decision-making at the bedside or in the clinic.

Projections of the incidence of COVID-19 in Japan and the potential impact of a Fall 2023 COVID-19 Vaccine (preprint)

Background: The study objective was to estimate the incidence of COVID-19 infection, hospitalization, and deaths in Japan from September 2023 to August 2024 and potential impact of a Fall 2023 COVID-19 vaccine for adults 18 years and older on these outcomes. Methods: A previously developed Susceptible Exposed Infected Recovered model for the United States (US) was adapted to Japan. The numbers of symptomatic infections, COVID-19 related hospitalizations, and deaths were calculated. Given differences in vaccination coverage, masking practices and social mixing patterns between the US and Japan, all inputs were updated to reflect the Japanese context. Vaccine effectiveness (VE) values are hypothetical, but predicted based on existing VE values of bivalent BA.4/BA.5 boosters against BA.4/BA.5 in Japan, from the VERSUS test-negative case-control study. Sensitivity analyses were performed. Results: The base case model predicts overall that there will be approximately 35.2 million symptomatic COVID-19 infections, 690,000 hospitalizations, and 62,000 deaths in Japan between September 2023 and August 2024. If an updated COVID-19 vaccine is offered to all adults aged 18 years and older in Fall 2023, the model predicts that 7.3 million infections, 275,000 hospitalizations and 26,000 deaths will be prevented. If vaccines are only given to those aged 65 years and older, only 2.9 million infections, 180,000 hospitalizations and 19,000 deaths will be prevented. Sensitivity analysis results suggest that hospitalizations and deaths prevented are most sensitive to initial vaccine effectiveness (VE) against infection and hospitalizations, and the waning rate associated with VE against infection. Symptomatic infections prevented was most sensitive to initial VE against infection and VE waning. Conclusions: Results suggest that a Fall 2023 COVID-19 vaccine would reduce total numbers of COVID-19 related infections, hospitalizations, and deaths.

Clinical impact and cost-effectiveness of the updated COVID-19 mRNA Autumn 2023 vaccines in Germany (preprint)

Objectives: To assess the potential clinical impact and cost-effectiveness of coronavirus disease 2019 (COVID-19) mRNA vaccines updated for Autumn 2023 in adults aged [≥]60 years and high-risk persons aged 30-59 years in Germany over a 1-year analytic time horizon (September 2023--August 2024). Methods: A compartmental Susceptible-Exposed-Infected-Recovered model was updated and adapted to the German market. Numbers of symptomatic infections, number of COVID-19 related hospitalisations and deaths, costs, and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio of an Autumn 2023 Moderna updated COVID-19 (mRNA-1273.815) vaccine was compared to no additional vaccination. Potential differences between the mRNA-1273.815 and the Autumn Pfizer-BioNTech updated COVID-19 (XBB.1.5 BNT162b2) vaccines, as well as societal return on investment for the mRNA-1273.815 vaccine relative to no vaccination, were also examined. Results: Compared to no Autumn vaccination, the mRNA-1273.815 campaign is predicted to prevent approximately 1,697,900 symptomatic infections, 85,400 hospitalisations, and 4,100 deaths. Compared to an XBB.1.5 BNT162b2 campaign, the mRNA-1273.815 campaign is also predicted to prevent approximately 90,100 symptomatic infections, 3,500 hospitalisations, and 160 deaths. Across both analyses we found the mRNA-1273.815 campaign to be dominant. Conclusions: The mRNA-1273.815 vaccine can be considered cost-effective relative to the XBB.1.5 BNT162b2 vaccine and highly likely to provide more benefits and save costs compared to no vaccine in Germany, and to offer high societal return on investment.

The potential clinical impact and cost-effectiveness of the updated COVID-19 mRNA Fall 2023 vaccines in the United States (preprint)

Objectives: To assess the potential clinical impact and cost-effectiveness of COVID-19 mRNA vaccines updated for Fall 2023 in adults [≥]18 years over a 1-year analytic time horizon (September 2023-August 2024). Methods: A compartmental Susceptible-Exposed-Infected-Recovered model was updated to reflect COVID-19 in summer 2023. Numbers of symptomatic infections, COVID-19 related hospitalizations and deaths, and costs and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio (ICER) of a Moderna updated mRNA Fall 2023 vaccine (Moderna Fall Campaign) was compared to no additional vaccination. Potential differences between the Moderna and the Pfizer-BioNTech Fall 2023 vaccines were examined. Results: Base case results suggest the Moderna Fall Campaign would decrease the expected 64.2 million symptomatic infections by 7.2 million (11%) to 57.0 million. COVID-19-related hospitalizations and deaths are expected to decline by 343,000 (-29%) and 50,500 (-33%), respectively. The Moderna Fall Campaign would increase QALYs by 740,880 and healthcare costs by $5.7 billion relative to No Vaccine, yielding an ICER of $7,700 per QALY gained. Using a societal cost perspective, the ICER is $2,100. Sensitivity analyses suggest that vaccine effectiveness, COVID-19 incidence, hospitalization rates and costs drive cost-effectiveness. With a relative vaccine effectiveness (rVE) of Moderna versus Pfizer-BioNTech of 5.1% for infection and 9.8% for hospitalization, use of the Moderna vaccine is expected to prevent 24,000 more hospitalizations and 3,300 more deaths than the Pfizer-BioNTech vaccine. Limitations and Conclusions: As COVID-19 becomes endemic, future incidence, including patterns of infection, are highly uncertain. Vaccine effectiveness of Fall 2023 vaccines is unknown, and it is unclear when a new variant that evades natural or vaccine immunity will emerge. Despite these limitations, the Moderna Fall 2023 vaccine can be considered cost-effective relative to no vaccine.

Impact of Differential Vaccine Effectiveness on COVID-19 Hospitalization Cases: Projections for 10 Developed Countries where Booster Vaccines were Recommended (preprint)

Background & Objectives: In a previous analysis, a decision-analytic model was used to analyze the clinical and economic impact of the differences in effectiveness between the two licensed mRNA COVID-19 booster vaccines, mRNA-1273 and BNT162b2, in 2022 for adults aged 18 years and older in the United States (US). In this analysis, the same model was used to estimate the impact that administering first booster doses with mRNA-1273 could have had on COVID-related hospitalizations and costs over a 6-month period in 10 developed countries (Australia, Canada, France, Germany, Italy, Japan, South Korea, Spain, United Kingdom [UK], and US), considering updated effectiveness data. Methods: The model was used to estimate number of hospitalizations and related costs using the actual vaccine distribution for the first COVID-19 booster from each country. These estimates were compared to a scenario where 100% of doses for that 6-month period was assumed to be mRNA-1273. The effectiveness of mRNA-1273 compared to BNT162b2 was estimated from real world data from the UK. Results: The total number of doses switched to the mRNA-1273 booster would range from 4.3 million in Spain to 39.4 million in Japan. The number of hospitalizations and associated hospitalization costs would be expected to fall in all countries, with the proportional decrease ranging from 1.1% (16,800 fewer) in Germany to 8.8% (25,100 fewer) in Australia. Conclusions: Real-world effectiveness data suggest that a booster dose of the mRNA-1273 vaccine may be more effective compared to other vaccines used for booster doses. Given this difference in effectiveness, results of this analysis demonstrate that switching to 100% mRNA-1273 boosters would have reduced the number of hospitalizations and associated costs in each country during the first 6 months of the omicron period.

The Potential Clinical Impact of Implementing Different COVID-19 Boosters in Fall 2022 in the United States (preprint)

Objective Emerging SARS-COV-2 variants are spurring the development of adapted vaccines as public health authorities plan for the fall vaccination strategy. We aimed to estimate the number of infections and hospitalizations prevented by three potential booster strategies in those ≥18 years of age in the United States: Boosting with Moderna’s licensed first generation monovalent vaccine mRNA-1273 (ancestral strain) starting in September 2022, boosting with Moderna’s candidate bivalent vaccine mRNA-1273.214 (ancestral + BA.1 variant of concern [VOC]) starting in September 2022, or boosting with Moderna’s updated candidate bivalent vaccine mRNA-1273.222 (ancestral + BA.4/5 VOC) starting 2 months later in November 2022 due to longer development timeline. Methods An age-stratified, transmission dynamic, Susceptible-Exposed-Infection-Recovered (SEIR) model, adapted from previous literature, was used to estimate the number of infections over time; the model contains compartments defined by both SEIR status and vaccination status. A decision tree was subsequently used to estimate the clinical consequences of those infections. Calibration was performed so the model tracks the actual course of the pandemic up to the present time. Results Vaccinating with mRNA-1273(Sept), mRNA-1273.214(Sept), and mRNA-1273.222(Nov) is predicted to reduce infections by 34%, 40%, and 18%, respectively, over a 6-month time horizon (September-February) compared to no booster. Similarly, boosting in September prevents substantially more hospitalizations than starting to boost in November with a more effective vaccine (42%, 48%, and 25% for mRNA-1273, mRNA-1273.214, and mRNA-1273.222, respectively, at 6 months compared to no booster). Sensitivity analyses around transmissibility, vaccine coverage, masking, and waning of natural and vaccine-induced immunity changed the magnitude of cases prevented but boosting with mRNA-1273.214 in September consistently prevented more cases of infection and hospitalization than the other two strategies. Limitations and Conclusions With the emergence of new variants, key characteristics of the virus that affect estimates of spread and clinical impact also evolve, making estimation of these parameters difficult, especially in heterogeneous populations. Our analysis demonstrated that vaccinating with the bivalent mRNA-1273.214 booster was more effective over a 6-month period in preventing infections and hospitalizations with a BA.4/5 subvariant than the tailored vaccine, simply because it could be deployed 2 months earlier. We conclude that there is no advantage to delay boosting until a BA.4/5 vaccine is available; earlier boosting with mRNA-1273.214 will prevent the most infections and hospitalizations.

Intensive mothering in the time of coronavirus

We investigated experiences of mothers of school-age children in Central New York during a time of remote education due to COVID-19. We extend the concept of intensive mothering, characterized by the expectation that mothers are constantly available to meet their children's needs, and examine mothers? intersectional identities related to their experience of remote education. Mothers working from home often went back and forth between work and school in what we refer to as a simultaneous shift. Essential workers were engaged in a sequential shift, engaging with children's schoolwork after work and trading off with partners. Mothers took on multiple roles during the pandemic which led to role strain. In extreme cases, multiple roles could be impossible to fill, leading to a situation of role conflict where the demands of one role made it impossible to meet the needs of another role. Mothers of children of color experienced more negative interactions with schools than White mothers. Mothers of children with disabilities spent extended time on remote schooling. A limitation of our study is that we only interviewed people in Central New York and cannot generalize the results of our research to a larger population. Another limitation to our approach was that we have little information on how fathers experienced work and overseeing children's schoolwork. Future research should examine how mothering may have changed after children returned to school.

Clinical and Economic Impact of Differential COVID-19 Vaccine Effectiveness in the United States (preprint)

Background: In the United States (US), three vaccines are currently available for primary vaccination and booster doses to prevent coronavirus disease 2019 (COVID-19), including the 2-dose messenger ribonucleic acid (mRNA) BNT162b2 (COMIRNATY(R), Pfizer Inc) and mRNA-1273 (SPIKEVAX(R), Moderna Inc) vaccines, which are preferred by the Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practice (ACIP), and the adenovirus vector Ad26.COV2.S (Johnson & Johnson) vaccine. A substantial body of evidence has now been published on the real-world effectiveness and waning of the primary series and booster doses against specific SARS-CoV2- variants. The study objective was to determine the clinical and economic impact of differences in effectiveness between mRNA-1273 and BNT162b2 booster vaccinations over one year (2022) in US adults [≥]18 years. Methods: A decision analytic model was used to compare three mRNA booster market share scenarios: (1) Current Scenario, where the booster mix observed in December 2021 continues throughout 2022; (2) mRNA-1273 Scenario, where the only booster administered in 2022 is mRNA-1273, and (3) BNT162b2 Scenario, where the only booster administered in 2022 is BNT162b2. Analyses were performed from the US healthcare system perspective. Sensitivity analyses were performed to explore the impact of COVID-19 incidence in the unvaccinated population and vaccine effectiveness (VE) on model results. Results: In the Current Scenario, the model predicts 65.2 million outpatient visits, 3.4 million hospitalizations, and 636,100 deaths from COVID-19 in 2022. The mRNA-1273 Scenario reduced each of these outcomes compared to the Current Scenario. Specifically, 684,400 fewer outpatient visits, 48,700 fewer hospitalizations and 9,500 fewer deaths would be expected. Exclusive of vaccine costs, the mRNA-1273 Scenario is expected to decrease direct medical costs by $1.3 billion. Conversely, the BNT162b2 Scenario increased outcomes compared to the Current Scenario: specifically, 391,500 more outpatient visits, 34,500 more hospitalizations and 7,200 more deaths would be expected in 2022, costing an additional $946 million in direct medical costs. For both the mRNA-1273 and BNT162b2 booster scenarios, the percent change in direct treatment costs for COVID-19 is similar to the percent change in hospitalizations as the rate of hospitalizations is the driver of the overall costs. Changing the number of projected COVID-19 cases in 2022 by varying the incidence rate has a direct effect on model outcomes. Higher incidence rates leads to higher outpatient visits, hospitalizations and deaths for all scenarios. Varying VE has an inverse effect on model outcomes. All outcomes increase when VE is lower for all vaccines and decrease when VE is higher. In all cases, additional use of mRNA-1273 leads to fewer infection outcomes while additional use of BNT126b2 results to higher infection outcomes. Conclusion: As the real-world effectiveness evidence to date indicates that mRNA-1273 may be more effective at preventing COVID-19 infection and hospitalization over time than BNT-162b2, increasing the proportion of people receiving this as a booster are expected to reduce COVID-19-related outcomes and costs in 2022, regardless of COVID-19 incidence or variant.

Riding the waves: the ongoing impact of COVID-19 on a national surgical training cohort.

BACKGROUND: The World Health Organisation declared a global pandemic on the 11 March 2020 resulting in implementation of methods to contain viral spread, including curtailment of all elective and non-emergent interventions. Many institutions have experienced changes in rostering practices and redeployment of trainees to non-surgical services. Examinations, study days, courses, and conferences have been cancelled. These changes have the potential to significantly impact the education and training of surgical trainees. AIM: To investigate the impact of the COVID-19 pandemic on training, educational, and operative experiences of Irish surgical trainees. METHODS: Surgical trainees were surveyed anonymously regarding changes in working and educational practices since the declaration of the COVID-19 pandemic on 11 March 2020. The survey was circulated in May 2020 to both core and higher RCSI surgical trainees, when restrictions were at level five. Questions included previous and current access to operative sessions as well as operative cases, previous and current educational activities, access to senior-led training, and access to simulation-/practical-based training methods. A repeat survey was carried out in October 2020 when restrictions were at level two. RESULTS: Overall, primary and secondary survey response rates were 29% (n = 98/340) and 19.1% (n = 65/340), respectively. At the time of circulation of the second survey, the number of operative sessions attended and cases performed had significantly improved to numbers experienced pre-pandemic (p < 0.0001). Exposure to formal teaching and education sessions returned to pre-COVID levels (p < 0.0001). Initially, 23% of trainees had an examination cancelled; 53% of these trainees have subsequently sat these examinations. Of note 27.7% had courses cancelled, and 97% of these had not been rescheduled. CONCLUSION: Surgical training and education have been significantly impacted in light of COVID-19. This is likely to continue to fluctuate in line with subsequent waves. Significant efforts have to be made to enable trainees to meet educational and operative targets.

Proning related bilateral anterior ischaemic optic neuropathy in a patient with COVID-19 related acute respiratory distress syndrome.

BACKGROUND: Non-arteritic ischaemic optic neuropathy (NAION) is a rare but harmful complication of prone positioning. Prone mechanical ventilation is a therapeutic strategy which has been used extensively during the COVID-19 pandemic to treat acutely hypoxemic patients with COVID-19 related acute respiratory distress syndrome (ARDS). Though a small number of cases of unilateral NAION have been reported in patients testing positive for the SARS-CoV-2 virus, we describe what is to our knowledge, the first reported case of bilateral NAION occurring in a patient proned extensively for the treatment of COVID-19 related ARDS. We consider the potential aetiological factors leading to NAION after prone mechanical ventilation in patients with COVID-19 and suggest strategies to protect against its development. CASE PRESENTATION: We report a case of severe, irreversible, visual impairment secondary to bilateral anterior ION in a fifty-five-year-old male who underwent eight episodes of prone mechanical ventilation to treat COVID-19 related ARDS. Once weaned from his sedation he reported bilateral painless vision loss, and bedside ophthalmological assessment identified a reduced visual acuity of 3/30 unaided in the left eye and counting fingers in the right. Dilated indirect ophthalmoscopy revealed inferotemporal optic disc oedema with splinter haemorrhages in the right eye and mild disc oedema, temporal pallor, and nerve fibre layer haemorrhages inferiorly in the left eye. Humphrey visual field 24 - 2 testing confirmed a severely constricted visual field with macular sparing on the right and depressed inferonasal vision with preserved peripheral vision on the left eye. OCT disc imaging shortly after diagnosis revealed bilateral disc swelling and flame haemorrhages in the right eye. CONCLUSIONS: NAION is a devastating, but preventable complication of prone positioning, which may pose significant risk of vision loss in patients with COVID-19 related ARDS.

Opening a Space for Collaboration and Support in Ph.D. Programs

Research can be a very isolating experience for Ph.D. students. We created a forum for discussion among Ph.D. students to discuss the doctoral experience and generate ideas surrounding collaboration and dialogue using open space methodology. This paper explores isolation as an element of the social and community aspect of learning in a Ph.D. program. The onset of COVID-19 broadened the scope of our exploration and necessitated new adaptations for discussion and interaction. [For the complete volume, "American Association for Adult and Continuing Education Inaugural 2020 Conference Proceedings (Online, October 27-30, 2020)," see ED611534.]

GRP78 binds SARS-CoV-2 Spike protein and ACE2 and GRP78 depleting antibody blocks viral entry and infection in vitro (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 global pandemic, utilizes the host receptor angiotensin-converting enzyme 2 (ACE2) for viral entry. However, other host factors may also play major roles in viral infection. Here we report that the stress-inducible molecular chaperone GRP78 can form a complex with the SARS-CoV-2 Spike protein and ACE2 intracellularly and on the cell surface, and that the substrate binding domain of GRP78 is critical for this function. Knock-down of GRP78 by siRNA dramatically reduced cell surface ACE2 expression. Treatment of lung epithelial cells with a humanized monoclonal antibody (hMAb159), selected for its ability to cause GRP78 endocytosis and its safe clinical profile in preclinical models, reduces cell surface ACE2 expression, SARS-CoV-2 Spike-driven viral entry, and significantly inhibits SARS-CoV-2 infection in vitro. Our data suggest that GRP78 is an important host auxiliary factor for SARS-CoV-2 entry and infection and a potential target to combat this novel pathogen and other viruses that utilize GRP78.

Personal Protective Equipment (PPE) use among emergency eye care professionals in the UK during the COVID19 pandemic.

EEC staff were provided with rapidly changing personal PPE guidance by Public Health England (PHE) with specific subspecialty advice from the British Emergency Eye Care Society (BEECS) and the Royal College of Ophthalmologists (RCOphth) UK during the COVID19 pandemic. BEECS undertook a baseline survey of its members after the initial response from the RCOphth 16/3/20 mirroring Public Health England (PHE) advice and a follow- up survey after the guidance was updated on 9/4/20. A combined total of 84 responses were received. Improvements after RCOphth changes between the two surveys from hospital respondents showed increases in temperature screening (13%), scrub use (34%), use of aprons (31%), masks (4%), eye protection (35%), gloves (25%) and slit lamp guard (1%). Our findings demonstrate a positive and significant adaptation of PPE in response to change in guidance published by PHE, RCOphth and BEECS between 16/3/20 and 11/4/20. The COVID19 pandemic has rapidly taken over the normal activity of Ophthalmic departments creating unprecedented challenges. Following initial confusion and vulnerability expressed by EEC professionals to PPE guidance, most Trusts appear to have adapted and are doing similar things. The response has been swift and effective as a result of good team work and early advice from BEECS and the RCOphth. On the whole, management teams are listening.