Galaxy Training: A powerful framework for teaching!

There is an ongoing explosion of scientific datasets being generated, brought on by recent technological advances in many areas of the natural sciences. As a result, the life sciences have become increasingly computational in nature, and bioinformatics has taken on a central role in research studies. However, basic computational skills, data analysis, and stewardship are still rarely taught in life science educational programs, resulting in a skills gap in many of the researchers tasked with analysing these big datasets. In order to address this skills gap and empower researchers to perform their own data analyses, the Galaxy Training Network (GTN) has previously developed the Galaxy Training Platform (https://training.galaxyproject.org), an open access, community-driven framework for the collection of FAIR (Findable, Accessible, Interoperable, Reusable) training materials for data analysis utilizing the user-friendly Galaxy framework as its primary data analysis platform. Since its inception, this training platform has thrived, with the number of tutorials and contributors growing rapidly, and the range of topics extending beyond life sciences to include topics such as climatology, cheminformatics, and machine learning. While initially aimed at supporting researchers directly, the GTN framework has proven to be an invaluable resource for educators as well. We have focused our efforts in recent years on adding increased support for this growing community of instructors. New features have been added to facilitate the use of the materials in a classroom setting, simplifying the contribution flow for new materials, and have added a set of train-the-trainer lessons. Here, we present the latest developments in the GTN project, aimed at facilitating the use of the Galaxy Training materials by educators, and its usage in different learning environments.

Casirivimab and Imdevimab for the Treatment of Hospitalized Patients With COVID-19.

BACKGROUND: The open-label RECOVERY study reported improved survival in hospitalized, SARS-CoV-2 seronegative patients treated with casirivimab and imdevimab (CAS + IMD). METHODS: In this phase I/II/III, double-blind, placebo-controlled trial conducted prior to widespread circulation of Delta and Omicron, hospitalized COVID-19 patients were randomized (1:1:1) to 2.4 g or 8.0 g CAS + IMD or placebo, and characterized at baseline for viral load and SARS-CoV-2 serostatus. RESULTS: 1336 patients on low-flow or no supplemental (low-flow/no) oxygen were treated. The primary endpoint was met: in seronegative patients, the least-squares mean difference (CAS + IMD versus placebo) for time-weighted average change from baseline in viral load through day 7 was -0.28 log10 copies/mL (95% CI, -0.51 to -0.05; P = .0172). The primary clinical analysis of death or mechanical ventilation (death/MV) from day 6-29 in patients with high viral load had a strong positive trend but did not reach significance. CAS + IMD numerically reduced all-cause mortality in seronegative patients through day 29 (relative risk reduction, 55.6%; 95% CI, 24.2-74.0). No safety concerns were noted. CONCLUSIONS: In hospitalized COVID-19 patients on low-flow/no oxygen, CAS + IMD reduced viral load and likely improves clinical outcomes in the overall population, with the benefit driven by seronegative patients, and no harm observed in seropositive patients.

Pre-clerkship Teaching and Learning in the Virtual Learning Environment: Lessons Learned and Future Directions.

In response to the COVID-19 pandemic, we developed and implemented a theory-informed process to adapt a comprehensive pre-clerkship medical school curriculum to run in the virtual learning environment utilizing sociocultural learning theory and cognitive load theory. Of 124 student respondents, 45% rated virtual learning as very or extremely effective, and 49% as moderately effective. Positive aspects of virtual learning included effectiveness of chat moderators, displaying pronouns on Zoom, active learning technology, and captioning and transcription. Negative aspects included access to technology and feeling isolated from community. Overall course ratings, examination performance, and work hours did not differ pre- and post-implementation.

Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients With SARS-CoV-2 Infection: A Phase 2 Dose-Ranging Randomized Clinical Trial.

Importance: The monoclonal antibody combination of casirivimab and imdevimab reduced viral load, hospitalization, or death when administered as a 1200-mg or greater intravenous (IV) dose in a phase 3 COVID-19 outpatient study. Subcutaneous (SC) and/or lower IV doses should increase accessibility and/or drug supplies for patients. Objective: To assess the virologic efficacy of casirivimab and imdevimab across different IV and SC doses compared with placebo. Design, Setting, and Participants: This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study included outpatients with SARS-CoV-2 infection at 47 sites across the United States. Participants could be symptomatic or asymptomatic; symptomatic patients with risk factors for severe COVID-19 were excluded. Data were collected from December 15, 2020, to March 4, 2021. Interventions: Patients were randomized to a single IV dose (523 patients) of casirivimab and imdevimab at 300, 600, 1200, or 2400 mg or placebo; or a single SC dose (292 patients) of casirivimab and imdevimab at 600 or 1200 mg or placebo. Main Outcomes and Measures: The primary end point was the time-weighted average daily change from baseline (TWACB) in viral load from day 1 (baseline) through day 7 in patients seronegative for SARS-CoV-2 at baseline. Results: Among 815 randomized participants, 507 (282 randomized to IV treatment, 148 randomized to SC treatment, and 77 randomized to placebo) were seronegative at baseline and included in the primary efficacy analysis. Participants randomized to IV had a mean (SD) age of 34.6 (9.6) years (160 [44.6%] men; 14 [3.9%] Black; 121 [33.7%] Hispanic or Latino; 309 [86.1%] White); those randomized to SC had a mean age of 34.1 (10.0) years (102 [45.3%] men; 75 [34.7%] Hispanic or Latino; 6 [2.7%] Black; 190 [84.4%] White). All casirivimab and imdevimab treatments showed significant virologic reduction through day 7. Least-squares mean differences in TWACB viral load for casirivimab and imdevimab vs placebo ranged from -0.56 (95% CI; -0.89 to -0.24) log10 copies/mL for the 1200-mg IV dose to -0.71 (95% CI, -1.05 to -0.38) log10 copies/mL for the 2400-mg IV dose. There were no adverse safety signals or dose-related safety findings, grade 2 or greater infusion-related or hypersensitivity reactions, grade 3 or greater injection-site reactions, or fatalities. Two serious adverse events not related to COVID-19 or the study drug were reported. Conclusions and Relevance: In this randomized clinical trial including outpatients with asymptomatic and low-risk symptomatic SARS-CoV-2, all IV and SC doses of casirivimab and imdevimab comparably reduced viral load. Trial Registration: ClinicalTrials.gov Identifier: NCT04666441.

Efficacy and safety of a single dose of casirivimab and imdevimab for the prevention of COVID-19 over an 8-month period: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: There is an unmet need for COVID-19 prevention in patient populations who have not mounted or are not expected to mount an adequate immune response to complete COVID-19 vaccination. We previously reported that a single subcutaneous 1200 mg dose of the monoclonal antibody combination casirivimab and imdevimab (CAS + IMD) prevented symptomatic SARS-CoV-2 infections by 81·4% in generally healthy household contacts of SARS-CoV-2-infected individuals over a 1-month efficacy assessment period. Here we present additional results, including the 7-month follow-up period (months 2-8), providing additional insights about the potential for efficacy in pre-exposure prophylaxis settings. METHODS: This was a randomised, double-blind, placebo-controlled trial done in the USA, Romania, and Moldova in 2020-2021, before the emergence of omicron (B.1.1.529) and omicron-lineage variants. Uninfected and unvaccinated household contacts of infected individuals, judged by the investigator to be in good health, were randomly assigned (1:1) to receive 1200 mg CAS + IMD or placebo by subcutaneous injection according to a central randomisation scheme provided by an interactive web response system; randomisation was stratified per site by the test results of a local diagnostic assay for SARS-CoV-2 and age group at baseline. COVID-19 vaccines were prohibited before randomisation, but participants were allowed to receive COVID-19 vaccination during the follow-up period. Participants who developed COVID-19 symptoms during the follow-up period underwent RT-PCR testing. Prespecified endpoints included the proportion of previously uninfected and baseline-seronegative participants (seronegative-modified full analysis set) who had RT-PCR-confirmed COVID-19 in the follow-up period (post-hoc for the timepoints of months 2-5 and 6-8 only) and underwent seroconversion (ie, became seropositive, considered a proxy for any SARS-CoV-2 infections [symptomatic and asymptomatic]; prespecified up to day 57, post-hoc for all timepoints thereafter). We also assessed the incidence of treatment-emergent adverse events. This study is registered with ClinicalTrials.gov, NCT04452318. FINDINGS: From July 13, 2020, to Oct 4, 2021, 2317 participants who were RT-PCR-negative for SARS-CoV-2 were randomly assigned, of whom 1683 (841 assigned to CAS + IMD and 842 assigned to placebo) were seronegative at baseline. During the entirety of the 8-month study, CAS + IMD reduced the risk of COVID-19 by 81·2% (nominal p<0·0001) versus placebo (prespecified analysis). During the 7-month follow-up period, protection was greatest during months 2-5, with a 100% relative risk reduction in COVID-19 (nominal p<0·0001; post-hoc analysis). Efficacy waned during months 6-8 (post-hoc analysis). Seroconversion occurred in 38 (4·5%) of 841 participants in the CAS + IMD group and in 181 (21·5%) of 842 in the placebo group during the 8-month study (79·0% relative risk reduction vs placebo; nominal p<0·0001). Six participants in the placebo group were hospitalised due to COVID-19 versus none who received CAS + IMD. Serious treatment-emergent adverse events (including COVID-19) were reported in 24 (1·7%) of 1439 participants receiving CAS + IMD and in 23 (1·6%) of 1428 receiving placebo. Five deaths were reported, none of which were due to COVID-19 or related to the study drugs. INTERPRETATION: CAS + IMD is not authorised in any US region as of Jan 24, 2022, because data show that CAS + IMD is not active against omicron-lineage variants. In this study, done before the emergence of omicron-lineage variants, a single subcutaneous 1200 mg dose of CAS + IMD protected against COVID-19 for up to 5 months of community exposure to susceptible strains of SARS-CoV-2 in the pre-exposure prophylaxis setting, in addition to the post-exposure prophylaxis setting that was previously shown. FUNDING: Regeneron Pharmaceuticals, F Hoffmann-La Roche, US National Institute of Allergy and Infectious Diseases, US National Institutes of Health.

Prediction of the need for intensive oxygen supplementation during hospitalisation among subjects with COVID-19 admitted to an academic health system in Texas: a retrospective cohort study and multivariable regression model.

OBJECTIVE: SARS-CoV-2 has caused a pandemic claiming more than 4 million lives worldwide. Overwhelming COVID-19 respiratory failure placed tremendous demands on healthcare systems increasing the death toll. Cost-effective prognostic tools to characterise the likelihood of patients with COVID-19 to progress to severe hypoxemic respiratory failure are still needed. DESIGN: We conducted a retrospective cohort study to develop a model using demographic and clinical data collected in the first 12 hours of admission to explore associations with severe hypoxemic respiratory failure in unvaccinated and hospitalised patients with COVID-19. SETTING: University-based healthcare system including six hospitals located in the Galveston, Brazoria and Harris counties of Texas. PARTICIPANTS: Adult patients diagnosed with COVID-19 and admitted to one of six hospitals between 19 March and 30 June 2020. PRIMARY OUTCOME: The primary outcome was defined as reaching a WHO ordinal scale between 6 and 9 at any time during admission, which corresponded to severe hypoxemic respiratory failure requiring high-flow oxygen supplementation or mechanical ventilation. RESULTS: We included 329 participants in the model cohort and 62 (18.8%) met the primary outcome. Our multivariable regression model found that lactate dehydrogenase (OR 2.36), Quick Sequential Organ Failure Assessment score (OR 2.26) and neutrophil to lymphocyte ratio (OR 1.15) were significant predictors of severe disease. The final model showed an area under the curve of 0.84. The sensitivity analysis and point of influence analysis did not reveal inconsistencies. CONCLUSIONS: Our study suggests that a combination of accessible demographic and clinical information collected on admission may predict the progression to severe COVID-19 among adult patients with mild and moderate disease. This model requires external validation prior to its use.

Impact of prior vaccination with CovishieldTM and Covaxin® on mortality among symptomatic COVID-19 patients during the second wave of the pandemic in South India during April and May 2021: a cohort study.

BACKGROUND: COVID-19 vaccines were authorised for emergency use to mitigate the impact of the pandemic. This study evaluated the effect of prior vaccination with either Oxford Astra Zeneca's Covishield™ or Bharath Biotech's Covaxin® on mortality among symptomatic COVID-19 patients during the second wave of the pandemic in India. METHODOLOGY: In this cohort study comprising of RT-PCR confirmed symptomatic COVID-19 patients presenting during April and May 2021, the effect of prior vaccination on mortality (primary outcome), need for hospitalization, oxygen therapy, non-invasive ventilation (NIV) and intensive care unit (ICU) admission were assessed and expressed as risk ratio (RR) with 95% confidence intervals (CI). RESULTS: The mean (SD) age of the cohort (n = 4183) was 46.3 (15.5) years; 17.9% (748/4183) had received at least one dose of Covishield™ and 4.8% (201/4183) had received Covaxin®. Mortality was 0.2% (95% CI: 0.2% - 0.7%), 3.5% (1.9-5.2%), 6.2% (0.3-12%) and 12.9% (11.8-14.1%) among fully vaccinated (>2 weeks after two doses), partially vaccinated (>2 weeks after one dose or <2 weeks after two doses), indeterminate (<2 weeks after one dose) and unvaccinated patients respectively. The difference in mortality among unvaccinated vs. fully vaccinated was 12.7% (95% CI: 11.4-13.9%), unvaccinated vs. partially vaccinated was 9.4% (7.4-11.4%) and unvaccinated vs. indeterminate vaccinated was 6.8% (0.8-12.7%). On adjusted analysis, as compared to unvaccinated patients, at least one dose of vaccine reduced the need for hospitalization (RR: 0.40; 95% CI: 0.35-0.47), oxygen (0.33; 0.27-0.40), NIV (0.23; 0.17-0.32), ICU admission (0.18; 0.12-0.27) and mortality (0.18; 0.11-0.29). CONCLUSION: Among symptomatic COVID-19 patients, prior vaccination with Covishield ™ or Covaxin® impacted the severity of illness and reduced mortality during a period of widespread delta variant circulation. Full vaccination conferred greater protection than partial vaccination.

Incidence of venous thrombotic events and events of special interest in a retrospective cohort of commercially insured US patients.

OBJECTIVE: To estimate the US incidence of thrombotic events and related rare diagnoses. DESIGN: Claims-based retrospective cohort study of incidence. SETTING: US commercial health insurance administrative claims database. PARTICIPANTS: Adults 25-64 years of age between 2015 and 2019 with a minimum of 12 consecutive thrombosis-free months of continuous enrolment beginning 2014 were selected. MAIN OUTCOMES: Age (10-year intervals) and sex stratum-specific incidence rates per 100 000 person-years were determined for venous thromboembolism (VTE), cerebral venous thrombosis (CVT) and other major venous thrombotic events, and events of special interest, including immune thrombocytopenic purpura (ITP), haemolytic-uremic syndrome (HUS) and heparin-induced thrombocytopenia (HIT). RESULTS: Of 13 249 229 enrollees (half female/male), incidence of venous thromboembolic events (deep vein thrombosis (DVT), pulmonary embolism (PE), CVT or other major venous thrombotic conditions) was 247.89 per 100 000 person-years (95% CI: 245.96 to 249.84). Incidence of VTE was 213.79 with ICD codes alone (95% CI: 211.99 to 215.59) and 129.34 (95% CI: 127.95 to 130.75) when also requiring a filled anticoagulation prescription or an inferior vena cava (IVC) filter. Incidence was 6.37 for CVT (95% CI: 6.07 to 6.69), 26.06 for ITP (95% CI: 25.44 to 26.78), 0.94 for HUS (95% CI: 0.82 to 1.06) and 4.82 for HIT (95% CI: 4.56 to 5.10). The co-occurrence of CVT with either ITP or HIT (diagnoses within 14 days of one another) was 0.090 (95% CI: 0.06 to 0.13). Incidence tended to increase with age and was higher for women under 55. Incidence for CVT, HUS and CVT with ITP or HIT was higher for women in all age groups. Incidence of PE and CVT increased significantly over the 5-year period, while DVT rates decreased. CONCLUSIONS: These results are the first US estimates for the incidence of thrombotic and rare events of interest in a large, commercially insured US population. Findings provide a critically important reference for determining excess morbidity associated with COVID-19 and more generally for vaccine pharmacovigilance.

Managing expansions in medical students' clinical placements caused by curricular transformation: perspectives from four medical schools.

Many challenges could occur that result in the need to handle an increase in the number of medical student clinical placements, such as curricular transformations or viral pandemics, such as COVID 19. Here, we describe four different institutions' approaches to addressing the impact of curricular transformation on clerkships using an implementation science lens. Specifically, we explore four different approaches to managing the 'bulge' as classes overlap in clerkships Curriculum leaders at four medical schools report on managing the bulge of core clinical placements resulting from reducing the duration of the foundational sciences curriculum and calendar shifts for the respective clerkship curriculum. These changes, which occurred between 2014 and 2018, led to more students being enrolled in core clinical rotations at the same time than occurred previously. Schools provided respective metrics used to evaluate the effectiveness of their bulge management technique. These data typically included number of students affected in each phase of their curricular transformation, performance on standardized examinations, and student and faculty feedback. Not all data were available from all schools, as some schools are still working through their 'bulge' or are affected by COVID-19. There is much to be learned about managing curricular transformations. Working on such endeavors in a learning collaborative such as the AMA Accelerating Change in Medical Education Initiative provided support and insights about how to survive, thrive and identifying lessons learned during curricular transformation.

ITE Traffic Bowl 12th Annual Grand Championship

For the second consecutive year, the annual Institute of Transportation Engineers (ITE) Collegiate Traffic Bowl Grand Championship Tournament was held in a virtual format due to the COVID-19 pandemic. The individual ITE District Traffic Bowl Tournaments were also held virtually. In 2021, 56 ITE Student Chapters formed teams so that more than 190 student members across Canada and the US could test their knowledge of ITE, transportation planning, and engineering (along with a few fun categories) to qualify for the 12th Annual Grand Championship Tournament, conducted in July as a part of the virtual ITE Annual Meeting. The schools qualifying to compete in the Grand Championship include Brigham Young University, NYU Tandon School of Engineering, Oregon State University, Penn State University, University of Arkansas, Clemson University, University of Florida and the University of Minnesota.

We Have No Choice but to Transform: The Future of Medical Education After the COVID-19 Pandemic.

Medical education exists to prepare the physician workforce that our nation needs, but the COVID-19 pandemic threatened to disrupt that mission. Likewise, the national increase in awareness of social justice gaps in our country pointed out significant gaps in health care, medicine, and our medical education ecosystem. Crises in all industries often present leaders with no choice but to transform-or to fail. In this perspective, the authors suggest that medical education is at such an inflection point and propose a transformational vision of the medical education ecosystem, followed by a 10-year, 10-point plan that focuses on building the workforce that will achieve that vision. Broad themes include adopting a national vision; enhancing medicine's role in social justice through broadened curricula and a focus on communities; establishing equity in learning and processes related to learning, including wellness in learners, as a baseline; and realizing the promise of competency-based, time-variable training. Ultimately, 2020 can be viewed as a strategic inflection point in medical education if those who lead and regulate it analyze and apply lessons learned from the pandemic and its associated syndemics.

REGEN-COV® antibody cocktail bioanalytical strategy: comparison of LC-MRM-MS and immunoassay methods for drug quantification.

Aim: In response to the COVID-19 pandemic, Regeneron developed the anti-SARS-CoV-2 monoclonal antibody cocktail, REGEN-COV® (RONAPREVE® outside the USA). Drug concentration data was important for determination of dose, so a two-part bioanalytical strategy was implemented to ensure the therapy was rapidly available for use. Results & methodology: Initially, a liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) assay, was used to analyze early-phase study samples. Subsequently, a validated electrochemiluminescence (ECL) immunoassay was implemented for high throughput sample analysis for all samples. A comparison of drug concentration data from the methods was performed which identified strong linear correlations and for Bland-Altman, small bias. In addition, pharmacokinetic data from both methods produced similar profiles and parameters. Discussion & conclusion: This novel bioanalytical strategy successfully supported swift development of a critical targeted therapy during the COVID-19 public health emergency.

COVID-19 prevention with subcutaneous administration of the monoclonal antibodies casirivimab and imdevimab: Subgroup analysis in participants with cardiovascular disease and diabetes

Background In a Phase 3 prevention trial, the monoclonal antibody combination casirivimab and imdevimab (REGEN-COVTM) administered subcutaneously (SC) prevented symptomatic SARS-CoV-2 infection in asymptomatic adults/adolescents living in the same household as a SARS-CoV-2-infected individual (index case). Individuals with cardiovascular disease (CVD) and/or diabetes are at increased risk of moderate/severe COVID-19. Methods Uninfected individuals ≥12 years, identified ≤96 hours of index case being diagnosed SARS-CoV-2 positive, were randomized 1:1 to REGEN-COV 1200mg SC or placebo. The primary endpoint was the proportion of participants who developed symptomatic infection (COVID-19) during the 28-day efficacy assessment period among those who were SARS-CoV-2 RT-qPCR negative and without evidence of immunity (seronegative) at baseline. A post-hoc analysis assessed efficacy in participants with CVD (including hypertension) and/or diabetes. Overall safety is reported. Results The study included SARS-CoV-2 RT-qPCR negative participants at baseline (n=2067). There was an 81.4% relative risk reduction (RRR) of symptomatic infection with REGEN-COV in the overall seronegative population (n=1505;Figure 1;Table 1). In participants with CVD (n=332) or diabetes (n=103), the RRRs of developing symptomatic infection with REGEN-COV versus placebo were 54.9% and 69.0%, respectively. Similar results were observed when analyses were performed regardless of baseline serology status. Treatment-emergent adverse events occurring at ≥2% included COVID-19, asymptomatic COVID-19, headache, and injection-site reaction (Table 2). Conclusions In study participants with CVD and/or diabetes, who are known to be at increased risk of severe disease if infected, treatment with REGEN-COV SC reduced the risk of developing symptomatic SARS-CoV-2 infection, consistent with the overall study results..

REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19.

BACKGROUND: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. METHODS: In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated. RESULTS: Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups. CONCLUSIONS: REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.).

Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19.

BACKGROUND: REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown. METHODS: We randomly assigned, in a 1:1 ratio, participants (≥12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARS-CoV-2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-CoV-2 infection (as measured by reverse-transcriptase-quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity). RESULTS: Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P<0.001). In weeks 2 to 4, a total of 2 of 753 participants in the REGEN-COV group (0.3%) and 27 of 752 participants in the placebo group (3.6%) had symptomatic SARS-CoV-2 infection (relative risk reduction, 92.6%). REGEN-COV also prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%). Among symptomatic infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV than with placebo (1.2 weeks and 3.2 weeks, respectively), and the duration of a high viral load (>104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted. CONCLUSIONS: Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04452318.).

Anxiety, PTSD, and stressors in medical students during the initial peak of the COVID-19 pandemic.

PURPOSE: To assess psychological effects of the initial peak phase of the COVID-19 pandemic on United States (US) medical students in clinical training to anticipate sequelae and prepare for future outbreaks. METHODS: Authors emailed a cross-sectional survey in April-May, 2020 to students in clinical training years at six US medical schools which included validated General Anxiety Disorder (GAD-7) and Primary Care-PTSD (PC-PTSD-5) screening tools, and asked students about pandemic-related stress and specific concerns. Authors used quantitative and thematic analysis to present results. RESULTS: Of 2511 eligible students, 741 responded (29.5%). Most students (84.1%) reported at least "somewhat" increased levels of stress and anxiety related to the pandemic. On the GAD-7, 34.3% showed mild, 16.1% moderate, and 9.5% severe anxiety symptoms, with 39.6% demonstrating no/minimal symptoms. One quarter (25.4%) screened positive for PTSD risk symptoms. Top concerns of students chosen from a pre-populated list included inadequate COVID-19 testing, undiagnosed or asymptomatic spread and racial or other disparities in the pandemic. In thematic analysis, students' reactions to removal from clinical learning included: understanding the need to conserve PPE (32.2%), a desire to help (27.7%), worry over infectious risk to others (25.4%) and self (21.2%), and lost learning opportunities (22.5%). Female students were significantly more likely to report anxiety and PTSD risk symptoms. Asian students had a greater risk of moderate anxiety and those underrepresented in medicine (UIM) had greater risk of moderate and severe anxiety symptoms compared to white students. CONCLUSIONS: During the initial peak phase of COVID-19, over 60% of US medical students screened positive for pandemic-related anxiety and one quarter were at risk for PTSD. Female and UIM students were significantly more affected. Medical schools should consider broad support of students, and targeted outreach to female and UIM students.

Lessons From Learners: Adapting Medical Student Education During and Post COVID-19.

In response to the COVID-19 pandemic, many medical schools suspended clinical clerkships and implemented newly adapted curricula to facilitate continued educational progress. While the implementation of these new curricula has been described, an understanding of the impact on student learning outcomes is lacking. In 2020, the authors followed Kern's 6-step approach to curricular development to create and evaluate a novel COVID-19 curriculum for medical students at the University of California San Francisco School of Medicine and evaluate its learning outcomes. The primary goal of the curriculum was to provide third- and fourth-year medical students an opportunity for workplace learning in the absence of clinical clerkships, specifically for students to develop clerkship-level milestones in the competency domains of practice-based learning and improvement, professionalism, and systems-based practice. The curriculum was designed to match students with faculty-mentored projects occurring primarily in virtual formats. A total of 126 students enrolled in the curriculum and completed a survey about their learning outcomes (100% response rate). Of 35 possible clerkship-level milestones, there were 12 milestones for which over half of students reported development in competency domains including practice-based learning and improvement, professionalism, and interpersonal and communication skills. Thematic analysis of students' qualitative survey responses demonstrated 2 central motivations for participating in the curriculum: identity as physicians-in-training and patient engagement. Six central learning areas were developed during the curriculum: interprofessional teamwork, community resources, technology in medicine, skill-building, quality improvement, and specialty-specific learning. This analysis demonstrates that students can develop competencies and achieve rich workplace learning through project-based experiential learning, even in virtual clinical workplaces. Furthermore, knowledge of community resources, technology in medicine, and quality improvement was developed through the curriculum more readily than in traditional clerkships. These could be considered as integral learning objectives in future curricular design.