Impact of the COVID-19 pandemic on human papillomavirus (HPV) vaccination among a national sample of United States adults ages 18–45: A cross-sectional study

To assess how the COVID-19 pandemic affected catch-up HPV vaccination among age-eligible adults (ages 18–45). The current study leverages a national, cross-sectional sample of US adults ages 18–45 years to assess the prevalence and determinants of COVID-19 pandemic-related disruptions to catch-up HPV vaccination in 2021. The sample was restricted to adults intending to receive the HPV vaccine. Multinomial logistic regression analysis was conducted to assess the probability of 1) pandemic-related HPV vaccination disruption and 2) uncertainty about pandemic-related HPV vaccination disruption. Report of ‘no pandemic-related HPV vaccination disruption' served as the reference category. Among adults intending to get the HPV vaccine (n = 1,683), 8.6 % reported pandemic-related HPV vaccination disruption, 14.7 % reported uncertainty about vaccination disruption, and 76.7 % reported no disruption. Factors associated with higher odds of pandemic-related vaccination disruption included non-English language preference (OR: 3.20;95 % CI: 1.99–5.13), being a parent/guardian (OR: 1.77;95 % CI: 1.18–2.66), having at least one healthcare visit in the past year (OR: 1.97;95 % CI: 1.10–3.53), being up-to-date on the tetanus vaccine (OR: 1.81;95 % CI: 1.19–2.75), and being a cancer survivor (OR: 2.57;95 % CI: 1.52–4.34). Catch-up HPV vaccination for age-eligible adults is a critical public health strategy for reducing HPV-related cancers. While a small percentage of adults reported pandemic-related disruptions to HPV vaccination, certain adults (e.g., individuals with a non-English language preference and cancer survivors) were more likely to report a disruption. Interventions may be needed that increase accessibility of catch-up HPV vaccination among populations with reduced healthcare access during the pandemic. © 2022 The Authors

Authoritarianism, psychopathy, and resistance to wearing masks during the COVID-19 pandemic: A partial replication and extension of key findings.

Controversial recent research suggests Americans with more authoritarian tendencies showed less concern about COVID-19 and self-report less mask wearing. The present study set out to replicate this result with a larger sample. The study also sought to extend the original research by investigating how the Dark Triad traits of narcissism, psychopathy, and Machiavellianism are related 1 COVID-19 attitudes and behaviors. Nine-hundred ninety-six United States high school graduates were asked 8 questions about their level of concern about the effects of the virus on health and finances, how frequently they wore masks, which authority figures they trusted, and whether China was responsible for the virus. Correlational and regression analyzes showed that authoritarianism, Machiavellianism, narcissism, and psychopathy were all negatively related to self-reported mask wearing. An explanation is offered for an apparent contradiction between the presented results and studies that showed authoritarian support for lockdowns early during the outbreak.

Social Work Students’ Self-Efficacy Toward Direct Practice Skills in Field Education Using Virtual Simulations and Scripted Role Plays

Simulations with professional actors and scripted role plays with peers are effective methods to increase direct practice skills. However, little is known about how simulations or scripted role plays conducted virtually can influence social work students' practice self-efficacy. MSW students enrolled in field seminar courses across two universities were invited to participate in an exploratory, repeated measures assessment utilizing the Counselor Activity Self-Efficacy Scales (CASES). One university (n=100) implemented the use of standardized clients, played by professional actors within field seminar;the other university (n=61) implemented scripted, peer-led role plays. Significant differences were found in pre/post scores among MSW students that participated in simulated client experiences within their field seminar. Simulations and scripted peer role plays may need to be more integrated into social work curricula when opportunities for in-person direct practice skill development are limited due to hybrid or fully remote field placements. Applied learning in social work education must be re-envisioned so programs can prepare MSW students to be effective practitioners in today’s rapidly changing environment. © 2022 Authors,.

Racial/ethnic disparities of cancer treatment disruptions among patients with breast cancer with SARS-CoV-2 infection: An analysis of the ASCO Survey on COVID-19 in Oncology Registry

Background: The COVID-19 pandemic has led to disruptions in cancer treatment delivery among breast cancer patients in the U.S. However, it is currently unknown whether racial/ethnic disparities exist in cancer treatment disruptions among patients with breast cancer and SARS-CoV-2 infection. Methods: We obtained data from the ASCO Survey on COVID-19 in Oncology Registry (March 2020-July 2021) describing breast cancer patients diagnosed with SARS-CoV-2 during their care treated at 46 practices across the US. Data included patient demographics, SARS-CoV-2 diagnosis and treatment, breast cancer characteristics, and modifications to cancer treatment plans. Breast cancer treatment delay or discontinuation (TDD) was defined as any treatment postponed more than two weeks from the originally scheduled date. We computed adjusted odds ratios (aOR) using multivariable logistic regression, accounting for non-independence of patients within hospitals to evaluate racial/ethnic disparities of TDD. Multivariable models were adjusted for age, sex, number of comorbidities, cancer extent, ECOG performance score, pandemic period based on case peaks (< 06/2020, 06-12/2020, 01-07/2021), and COVID-19 severity (death/hospitalization/ICU admission/mechanical ventilation). Results: Breast cancer patients (n = 804) with SARS-CoV-2 were mostly aged 50 years and above (75%) and urban residents (83%). The racial/ethnic makeup of the sample included: 13.3% non-Hispanic Black/African American (NH-Black), 11.7% Hispanic/Latinx, 4.9% American Indian/Alaskan Native (NH-AI/ AN), 4.6% NH-Asian, and 65% NH-White. At SARS-CoV-2 diagnosis, 736 patients (91%) were scheduled to receive drug-based therapy (78%), radiation therapy (8%), or surgery (6%), of whom 39% experienced TDD. Across treatment modalities, the most commonly reported TDD reason from the clinic perspective was the patient's COVID-19 disease (∼90%). Overall, NH-Black (62%), Hispanic/Latinx (44%), and NH-Asian (42%) adults with breast cancer and SARS-CoV-2 were more likely to experience TDD versus NH-White adults (34%) (p < 0.001). In multivariable analyses, NH-Black cancer patients were more likely to experience TDD compared to NH-White patients (aOR: 3.12, 95% CI: 1.96-5.47). The data suggest Hispanic/Latinx (aOR: 1.34, 95% CI: 0.78-2.30) breast cancer patients may also experience TDD, although not statistically significant. No association was observed among NH-Asian (aOR: 1.16, 95% CI: 0.50-2.73) or NH-AI/AN (aOR: 0.64, 95% CI: 0.28-1.52) breast cancer patients with TDD. Conclusions: Black or African American breast cancer patients are more likely to experience cancer care disruptions during the pandemic. Future research should evaluate the long-term impacts of care disruptions on breast cancer outcomes among minoritized US communities.

The role of rurality in cancer treatment disruptions among patients with cancer diagnosed with SARS-CoV-2: An analysis of the ASCO Survey on COVID-19 in Oncology Registry

Background: U.S. rural cancer patients experience multifactorial barriers to cancer treatment;however, little is known about the impact of the pandemic on cancer treatment delays or discontinuations (TDD) in the rural context. Our objective was to evaluate the role of rurality at both the patient and clinic level on cancer TDD among patients living with cancer with SARS-CoV-2 infection. Methods: We used data from the ASCO Survey on COVID-19 in Oncology Registry (March 2020-July 2021), which includes cancer patients diagnosed with SARS-CoV-2 (n = 3193). Data included patient demographics, SARSCoV- 2 treatment, cancer characteristics, and modifications to cancer treatment plans. Cancer-related TDD was defined as any treatment postponed > two weeks from the original scheduled date. Rurality was defined using the USDA Rural-Urban Commuting Area schema. We compared cancer characteristics, COVID-19 outcomes, and TDD by rurality of cancer patients, and TDD by rurality of oncology practices. We computed adjusted odds ratios (aOR) using multivariable logistic regression to evaluate rurality with TDD adjusting for age, race/ethnicity, sex, comorbidities, ECOG score, cancer extent, pandemic time period based on case peaks (< 06/2020, 06-12/2020, 01-07/2021), and COVID-19 severity. Results: Rural cancer patients (n = 499, 16%) with SARS-CoV-2 were mostly over 50 years (87%), female (57%), and NH-White (81%) with solid tumors (76%). Most rural patients received oncology treatment in urban areas (65%, p < 0.001). Rural patients were less likely to receive care through telemedicine (18%) compared to urban patients (26%) (p < 0.001). At SARS-CoV-2 diagnosis, rural patients were scheduled to receive drug-based therapy (72%), radiation therapy (8%), surgery (4%), or transplant (1%). Rural versus urban cancer patients with SARS-CoV-2 were less likely to experience TDD (41% vs. 51%) (p < 0.001). Among patients treated at rural oncology clinics, urban cancer patients were more likely to experience TDD (65%) compared with rural patients (47%) (p < 0.001). Similarly, among patients treated at urban oncology clinics, urban cancer patients were also more likely to experience TDD (51%) compared with rural patients (38%) (p < 0.001). In multivariable analyses, rural cancer patients were 28% less likely to experience TDD (aOR:0.72, 95% CI: 0.55- 0.94) than urban cancer patients. Oncology practice rurality was not associated with TDD (aOR: 1.19, 95% CI: 0.81-1.76). Conclusions: Rural cancer patients were less likely to experience TDD than urban patients supporting the urban-rural paradox i.e., geographic distance to cancer care facilities is not consistently associated with treatment delivery in expected ways. Future work should focus on area-level factors of the rural cancer patient experience to disentangle potential reasons for TDD during the pandemic.

Disparities in cancer treatment delays or discontinuation among cancer patients diagnosed with SARS-CoV-2 infection: An analysis of the U.S. ASCO COVID-19 and cancer registry

Background: Due to societal factors in the US, racial/ethnic minority adults are disproportionately impacted by the COVID-19 pandemic, particularly those with existing comorbid conditions such as cancer. It is currently unknown whether disparities exist in cancer treatment delivery among racial/ethnic minority patients with cancer and SARS-CoV-2. Methods: Data were obtained from the ASCO COVID-19 and Cancer Registry (March 2020-July 2021), including data from cancer patients diagnosed with SARS-CoV-2 during their care (n=3193) at 60 practices across the US. Data included patient demographics, SARS-CoV-2 diagnosis and treatment, cancer clinical characteristics, and modifications to cancer treatment plans. Cancer treatment delay or discontinuation (TDD) was defined as any treatment postponed more than two weeks from the original scheduled date. We descriptively evaluated demographic and clinical characteristics, compared disparities in TDD by race/ethnicity and urban/rural residency, and evaluated reasons for TDD as reported by the clinics. We computed adjusted odds ratios (aOR) using multivariable logistic regression, accounting for non-independence of patients within hospitals to evaluate racial/ethnic disparities of TDD. Multivariable models were adjusted for age, sex, body mass index, number of comorbidities, cancer type, cancer extent, cancer status at SARS-CoV-2 diagnosis (progressing/stable) and SARS-CoV-2 severity (death/hospitalization/ICU admission/mechanical ventilation). Results: Cancer patients with SARS-CoV-2were mostly female (57%), urban residents (84%), and NH-White (66%);49% were 65+ years old. Most patients had solid tumors (75%). At SARS-CoV-2 diagnosis, 2403 patients (76%) were scheduled to receive drug-based therapy (69%), radiation therapy (7%), surgery (4%), or transplant (0.7%), of whom 49% experienced TDD. The most reported TDD reason from the clinic perspective was the patient's COVID-19 disease (90%). Overall, NH-Black (64%) and Hispanic (57%) with SARS-CoV-2 were more likely to experience TDD versus NH-White adults (46%) (p<0.001). This disparity was also observed across urban residing adults (p<0.001). Among rural adults, NH-AI/AN (75%) and NH-Black (61%) were more likely to experience TDD versus NH-White patients (39%). In multivariable analyses, disparities persisted, by NH-Black cancer patients with 92% (aOR:1.92, 95% CI:1.24-2.96) and Hispanic patients with 41% (aOR:1.41, 95% CI:1.03-1.91) higher odds of experiencing TDD. We observed consistent results among urban and rural subgroups. Conclusion: Racial/ethnic disparities exist in TDD among cancer patients with SARS-CoV-2 in urban and rural care settings. Future studies should evaluate the impacts of delays to cancer treatment delivery on cancer outcomes among minoritized communities in the US.

Research Experiences for Teachers in Machine Learning

Machine learning and Artificial Intelligence (AI) are national priority areas for research, education and workforce development. This work in progress paper describes a Research Experiences for Teachers program in sensors and machine learning launched in the summer of 2020. Motivated by national AI workforce needs, we designed a program that engaged high school teachers from STEM fields in machine learning research. In 2020, the program focused on AI algorithms for solar energy systems. Because of the COVID-19 conditions, the research experience was virtual and ran with a smaller teacher group than originally planned. The program included development of training content, algorithm and software training, research in solar energy monitoring, development of research reports and lesson plans, research presentations, and assessment. The assessment of the program included surveys, interviews, presentation observations, and follow-up in high school content delivery.

GETTING PREP'ED FOR PRIDE: PROVIDING PREP AT A LOCAL PRIDE EVENT DURING COVID-19

Introduction In attempts to further promote awareness and availability of HIV Pre-Exposure Prophylaxis (PrEP) within local LGBTQ+ communities a pop-up clinic was held at the 2021 Bournemouth Pride event. Patients were educated about PrEP, Point-of-Care tested for HIV and Syphilis and given the option of starting an event-based regimen to cover for risk over the Pride weekend. Methods Event-based PrEP was initiated in patients undertaking a self-completion triage form, consultation and pointof- care testing. Patients took the first dose immediately and left the consultation with two follow-up doses of PrEP with text reminders scheduled to promote adherence. All patients were offered a follow-up appointment, given access to STI screening and further information about chemsex harm minimisation. Results 8 patients were given event-based PrEP during the event. All patients were cis-male and identified as men who have sex with men. None of them reported previous PrEP use. All patients made follow-up appointments for continuation PrEP whilst at the event and all patients attended this and continued PrEP. At this follow up visit, all patients disclosed HIV risk at the event. No patients required further 'emergency' dosing after the event. 3 patients self-sourcing PrEP asked to be 'converted' to NHS supply and were booked into follow up clinics at the event. Discussion Owing to the successful local rollout of PrEP since November 2020, many of the event attendees were already accessing PrEP. However, presence at a community LGBTQ+ event helped to further promote awareness of PrEP and encouraged high risk patients to attend mainstream services.

Time Spent in the Electronic Health Record by Neurologists: Analyzing daily use inside and outside the clinic using EPIC Signal data

Objective: To quantify how long neurologists spend in the electronic health record (EHR). Background: Neurologists have extensive information needs for decision-making (e.g., neuroimaging, video-recordings) that are likely to affect time spent in the EHR. While EHRrelated burden is being increasingly studied due to the national spotlight on physician burnout, few studies have focused on neurology. Design/Methods: Data were obtained using Epic Signal, which provides detailed data on how long clinicians spent on different EHR interfaces. We focused on all neurologists from an academic health system in Florida who practiced during November 2019 to October 2020 inclusive. Our EHR outcome measures were time spent interacting with the EHR, time spent in the EHR outside scheduled clinic hours, inbox management, writing notes, and chart review. We reported the median and range of outcome measures because they had skewed distributions. We also assessed whether changes related to the coronavirus pandemic (e.g., telemedicine adoption) were associated with differences in EHR use via Wilcoxon signed-rank tests. Results: Our sample contained 2,286 physician-week observations (83 neurologists). They spent up to: 333.6 minutes/day (median:66.5, range:0.5-333.6) interacting with the EHR, 303.4 minutes/day (median:27.8, range:0.0-303.4) in the EHR outside scheduled hours, 45.6 minutes/day (median:3.4, range:0.0-45.6) in the In Basket, 240.3 minutes/day (median:31.1, range:0.0-240.3) writing notes, and 73.1 minutes/day (median:11.0, range:0.0-73.1) in clinical review. EHR measures were comparable before and during the pandemic. Conclusions: Similar to physicians in other specialties, neurologists spend a significant proportion of their clinical effort engaged with the EHR. Neurologists may benefit from interventions that reduce time spent in the EHR, such as after-hours EHR use and documentation.

EFFECTS of CASIRIVIMAB + IMDEVIMAB on SYMPTOM OUTCOMES in OUTPATIENTS with COVID-19

Background: Symptoms reduction is a crucial outcome to be considered when testing novel treatments for COVID-19. The goal was to assess the impact of casirivimab+imdevimab (cas+imd) dose/exposure on the trajectory and resolution time of symptoms in outpatients with COVID-19. Methods: Analysis used data from the COV-2067 trial (NCT04425629). Cas+imd was administered intravenously (total dose 1.2 to 8 g). Symptoms data were collected using SE-C19, a patient-reported survey developed de novo to assess the symptomatic course of COVID-19. Based on patients' responses on SE-C19, a Rasch analysis was used to derive a latent score to infer their overall underlying symptom severity. A direct response model was fitted to the latent score-time data to quantify the effects of dose/exposure, demographic and clinical characteristics on latent symptom trajectory. Symptoms resolution time was defined as time from randomization to the 1st day during which the patient scored "no symptom". Several parametric models were tested as structural model, assuming a known distribution, eg, exponential or Weibull, for time to symptoms resolution data. Risk variables (eg, binary treatment or categorical dose levels, exposure metrics, baseline demographic, clinical, and biological characteristics) were tested as covariates using a proportional hazard model. Results: Results from the direct response model suggest that each dose, as compared to placebo, remarkably reduced IT50 (time taken to achieve half of the maximal response of reducing symptom) by ∼40%. By excluding data from placebo arm, none of the tested doses or predicted exposures, were significant covariates on any of the model parameters. Results from the parametric regression analysis further confirmed that cas+imd (HR=1.25) is a major factor shortening the symptoms resolution time in a dose-and exposure-independent manner. Males (HR=1.13) have a shorter symptoms resolution time. Older age (HR=0.991), higher BMI (HR=0.988), and more severe baseline symptoms (HR=0.783 for moderate and 0.589 for severe) significantly contribute to longer symptoms resolution time. Conclusion: Treatment with cas+imd (1.2 g or above), rapidly resolved symptoms in outpatients in a dose-and exposure-independent manner as indicated by a direct response model using derived latent score and further confirmed by a survival analysis using time to symptoms resolution. In addition, symptom severity, age, BMI, sex were major risk factors affecting the symptoms resolution time.

CASIRIVIMAB and IMDEVIMAB COMBINATION PROVIDES LONG-TERM PROTECTION AGAINST COVID-19

Background:A previous report showed that a single 1200 mg subcutaneous (SC) dose of casirivimab and imdevimab (cas/imd) prevented symptomatic COVID-19 by 81.4% and reduced all SARS-CoV-2 infections (symptomatic and asymptomatic) by 66.4% in household contacts living with recently infected individuals over a 28-day period. While highly effective vaccines now exist for the prevention of COVID-19, a significant unmet need remains in patients who are unable to mount or maintain an adequate immune response to vaccination. Here we present additional results from 7-month follow-up period of the aforementioned study. Methods: In this randomized, double-blind, placebo-controlled Phase III trial, asymptomatic participants exposed to a SARS-CoV-2-infected household member were randomized 1:1 to a single SC dose of placebo or 1200 mg cas/imd (600 mg of each monoclonal antibody). Efficacy analyses include participants who were RT-qPCR negative for SARS-CoV-2 (no current infection) and seronegative for SARS-CoV-2 (no prior infection) at baseline. The trial consisted of a primary efficacy assessment period of 28 days (Month 1) and a 7-month follow-up period (Months 2-8). Results: Results from 842 placebo and 841 cas/imd RT-qPCR negative/seronegative enrolled participants (data through 04Oct2021, prior to emergence of Omicron) are presented. During the entirety of the 8-month study, cas/imd reduced the risk of symptomatic SARS-CoV-2 infections by 81.2% versus placebo (nominal P<0.0001;Table) and all SARS-CoV-2 infections (symptomatic and asymptomatic) by 68.2% versus placebo (nominal P<0.0001;Table). During Months 2-5, the risk of symptomatic and all infections were reduced by 100% and 89.5%, respectively (nominal P<0.0001). During Months 6-8 there was a resumption of symptomatic and all SARS-CoV-2 infections in the cas/imd group (19.9%;nominal P=0.6411 and 30.7%;nominal P=0.3967 risk reduction, respectively). Fewer cas/imd participants had a medically-attended visit versus placebo during the 8-months (1/841 [0.1%] vs 16/842 [1.9%], respectively). No new safety signals were identified for cas/imd during the follow-up period. Conclusion: During the 8-month study period, a 1200 mg SC dose of cas/imd prevented SARS-CoV-2 infections, with maximal protection through Month 5. The prolonged protection supports the use of cas/imd for the long-term prevention of COVID-19 against susceptible variants, offering a pre-exposure prophylaxis strategy for individuals who are unlikely to respond or be protected by vaccination.

VIRAL KINETICS in COVID-19 OUTPATIENTS TREATED with CASIRIVIMAB+IMDEVIMAB COMBINATION

Background: Casirivimab+imdevimab (hereinafter referred to as drug) remains vital in reducing hospitalization/death by 70% when administered early in the course of the infection. Our aim was to illustrate the mechanism of drug action in vivo and determine the magnitude of antiviral efficacy of various dose regimens given to outpatients with COVID-19, evaluating the presence of SARS-CoV-2 sero-antibody and ≥1 high-risk factor for developing severe COVID-19 illness as predictors of viral kinetics. Methods: Analysis data came from 2 clinical studies in SARS-CoV-2 infected outpatients with no or ≥1 risk factor for severe COVID-19 (NCT04425629 and NCT04666441), who received single dose of placebo or drug IV (300mg to 8g) or SC (600mg to 1.2g), had assessed viral load in nasopharyngeal swab and drug concentrations in serum (N=4500). The median number of viral load assessments per patient was 5 (range 1-8) within up to 14 days of follow-up time. Drug concentrations were predicted using the individual pharmacokinetic parameters yielded by a population model. The median patient age was 42 years, with similar proportion of males and females. The median viral load at baseline was 6.79 log10 copies/mL, and the median time of symptom onset was 3 days before study baseline. A standard target cell-limited model was used to estimate the time of infection and reconstruct viral kinetic profiles. Various relationships between exposure and resulting antiviral response were evaluated, where the drug could block de novo infection, increase the elimination rate of infected cells, or reduce viral production from infected cells. Results: The results support that the main mechanism of drug action is blocking de novo infection with an estimated decrease in the infectivity rate of 96.6%, for all dose regimens evaluated herein. High-risk factor for severe COVID-19 and baseline sero-antibody-positive/other status were associated with a 4.71% decrease and a 4.96% increase in the elimination rate of infected cells, respectively. The estimated median and 95th percentile of time to viral clearance (ie, viral count reaches below assay quantification limit) were 1.4 and 3.4 days shorter in drug vs placebo (median 10.6 vs 12.0 days, and 95th percentile 15.2 vs 18.6 days). Conclusion: All IV and SC casirivimab+imdevimab dose regimens evaluated herein showed similar near-maximal antiviral activity by blocking de novo infection;hence, shortening the time to virus clearance.

Vida Decision Support System: An International, Collaborative Project for COVID-19 Management with Integrated Modeling

The Vida Decision Support System (Vida) is an application of the Environment-Vulnerability-Decision-Technology (EVDT) integrated modeling framework specifically aimed at COVID-19 impact and response analysis. The development of Vida has been an international collaboration involving multidisciplinary teams of academics, government officials (including public health, economics, environmental, and demographic data collection officials), and others from six states: Angola, Brazil, Chile, Indonesia, Mexico, and the United States. These collaborators have been involved with the identification of decision support needs, the surfacing and creation of relevant data products, and the evaluation of prototypes, with the vision of creating an openly available online platform that integrates earth observation instruments (Landsat, VIIRs, Planet Lab's PlanetScope, NASA's Socioeconomic Data and Applications Center, etc.) with in-situ data sources (COVID-19 case data, local demographic data, policy histories, mobile device-based mobility indices, etc.). Vida both visualizes historical data of relevance to decision-makers and simulates possible future scenarios. The modeling techniques used include system dynamics for public health, EO-based change detection and machine learning for environmental analysis, and discrete-event simulation of policy changes and impacts. In addition to the direct object of this collaboration (the development of Vida), collaborators have also benefited from sharing individual COVID-19-related insights with the network and from considering COVID-19 response in a more integrated fashion. This work outlines the Vida Decision Support System concept and the EVDT framework on which it is based. The international team is using Vida to evaluate the outcomes in several large cities regarding COVID cases, environmental changes, economic changes and policy decisions. It provides an overview of the overlapping and diverging needs and data sources of each of the collaborating teams, as well as how each of those teams have contributed to the development of Vida. The current state of the Vida prototypes and plans for future development will be presented. Additionally, this work will discuss the lessons learned from this development process and their relevance to other integrated applications. Copyright © 2021 by the International Astronautical Federation (IAF). All rights reserved.

Casirivimab and Imdevimab for Treatment of Hospitalized Patients with COVID-19 Receiving Low Flow or No Supplemental Oxygen

Background. Casirivimab and imdevimab (CAS/IMDEV) is authorized for emergency use in the US for outpatients with COVID-19. We present results from patient cohorts receiving low flow or no supplemental oxygen at baseline from a phase 1/2/3, randomized, double-blinded, placebo (PBO)-controlled trial of CAS/IMDEV in hospitalized patients (pts) with COVID-19. Methods. Hospitalized COVID-19 pts were randomized 1:1:1 to 2.4 g or 8.0 g of IV CAS/IMDEV (co-administered) or PBO. Primary endpoints were time-weighted average (TWA) change in viral load from baseline (Day 1) to Day 7;proportion of pts who died or went on mechanical ventilation (MV) through Day 29. Safety was evaluated through Day 57. The study was terminated early due to low enrollment (no safety concerns). Results. Analysis was performed in pooled cohorts (low flow or no supplemental oxygen) as well as combined treatment doses (2.4 g and 8.0 g). The prespecified primary virologic analysis was in seronegative (seroneg) pts (combined dose group n=360;PBO n=160), where treatment with CAS/IMDEV led to a significant reduction in viral load from Day 1-7 (TWA change: LS mean (SE): -0.28 (0.12);95% CI: -0.51, -0.05;P=0.0172;Fig. 1). The primary clinical analysis had a strong positive trend, though it did not reach statistical significance (P=0.2048), and 4/6 clinical endpoints prespecified for hypothesis testing were nominally significant (Table 1). In seroneg pts, there was a 47.0% relative risk reduction (RRR) in the proportion of pts who died or went on MV from Day 1-29 (10.3% treated vs 19.4% PBO;nominal P=0.0061;Fig. 2). There was a 55.6% (6.7% treated vs 15.0% PBO;nominal P=0.0032) and 35.9% (7.3% treated vs 11.5% PBO;nominal P=0.0178) RRR in the prespecified secondary endpoint of mortality by Day 29 in seroneg pts and the overall population, respectively (Fig. 2). No harm was seen in seropositive patients, and no safety events of concern were identified. Conclusion. Co-administration of CAS/IMDEV led to a significant reduction in viral load in hospitalized, seroneg pts requiring low flow or no supplemental oxygen. In seroneg pts and the overall population, treatment also demonstrated clinically meaningful, nominally significant reductions in 28-day mortality and proportion of pts dying or requiring MV.