Safety, Tolerability, and Viral Pharmacodynamics of the IgG Monoclonal Antibody Sotrovimab Administered via Intramuscular Injection for the Treatment of Early Mild-to-Moderate COVID-19

Background. There is a continued need for therapeutics for the treatment of COVID-19, including intramuscular (IM) agents, which will enable broader use across a variety of healthcare delivery settings. Methods. COMET-PEAK (NCT04779879) is a 3-part study evaluating the safety, tolerability, pharmacokinetics (Part A), and viral pharmacodynamics (PD) of sotrovimab as treatment in adults >= 18 years with early mild/moderate COVID-19. In Parts B and C, the safety, tolerability and viral PD of sotrovimab administered as a 500 mg intravenous (IV) infusion or as a 500 mg or 250 mg IM injection, respectively, was evaluated. The primary objective for Parts B and C was to compare the virologic response of sotrovimab IM to IV, with an endpoint of mean area under the curve (AUC) of SARS-CoV-2 viral load as measured by qRT-PCR from Day 1 to Day 8 (AUCD1-8) in nasopharyngeal swabs and predefined 90% confidence interval (CI) limits of 0.5-2.0 indicating equivalence. Results. A total of 167 and 157 participants were enrolled in Part B and C, respectively, from February-July 2021. The median age of participants was 47 and 42 years in Part B and C, respectively, and ~50% had >= 1 risk factor for progression to severe disease. The viral load at baseline and through Day 29 of follow-up for each arm is shown in Table 1 and Figure 1. The primary objective was met for both study parts: the ratio of the least square geometric mean viral load AUC(D1-8) of sotrovimab IM vs IV was 1.04 (90% CI, 0.98, 1.09) and 1.02 (90% CI, 0.94, 1.11), for Part B and C, respectively. Through Day 29 of follow-up, the most common adverse event was injection site reactions (ISRs) in the IM arms. A total of 10 (12%) participants in the 500 mg IM group and 4 (5%) participants in the 250 mg IM group experienced an ISR, all Grade 1. Serious adverse events were uncommon, and related to COVID-19 progression, including one death in the 250 mg IM arm (Table 2). ISRs aside, there were few treatment-related AEs (2/84 IV, 1/82 IM) in Part B, none serious. Conclusion. IM administration of sotrovimab 500 mg and 250 mg each demonstrated equivalence to 500 mg sotrovimab IV in viral load assessments. Overall, there were no treatment-related serious AEs and sotrovimab was well tolerated. An 500 mg IM formulation will allow for expanded treatment potential with sotrovimab.

Reframing mergers and acquisitions around stakeholder relationships: Economic, political and social processes

Among the significant repercussions of the coronavirus pandemic is escalating public questioning of the desirability and sustainability of the market economy and the societal role of business. These concerns are linked to merger and acquisition (M and A) activity, with significant disruptive consequences for stakeholder relationships and their management. This book explores these changes, moving away from the traditional focus on the financial and strategic aspects of M and A and its rational, technocratic approach. © 2023 Taylor and Francis. All rights reserved.

Urogynecology patient satisfaction with telemedicine during the COVID-19 pandemic in the first u.s. epicenter

Objective: The COVID-19 pandemic changed the practice of medicine, requiring rapid reorganization and flexibility of healthcare delivery. Guidelines for urogynecologic patient care during the pandemic discuss deferring in-person visits, but little is known about patient satisfaction with telemedicine for a broad range of urogynecologic conditions. Methods: We performed a cross-sectional survey study following a retrospective review of all urogynecologic telemedicine visits from 3/1/2020 to 3/31/2021 at a NewYork City (NYC) tertiary care center inManhattan. Live, two-way synchronous video visits were performed unless there was an inadequate connection necessitating a telephone visit. Patients were then emailed a 19-question survey and electronic consent. The survey queried patient satisfaction with subcategories for scheduling, technology, provider interaction, fulfillment of personal needs, and overall satisfaction (Fig 1). For those who did not complete the survey electronically, phone interviews and consent were conducted. Responses were recorded using the Likert scale and grouped as either satisfied ('strongly agree' and 'agree') versus dissatisfied ('strongly disagree,' 'disagree,' and 'neither agree or disagree'). Visits were categorized by chief complaint, including urinary tract infection (UTI), prolapse, incontinence, overactive bladder/lower urinary tract symptoms/bladder pain syndrome, surgical counseling, vulvovaginal symptoms, or other (e.g., postpartum consult). Chi-square analysis was performed to assess for differences in satisfaction among different demographic groups as well as by visit type. Results: There were 256 telemedicine visits during the study period, and 88 patients completed the survey (34% unadjusted response rate). There were 77 video visits (87.5%) and 11 telephone visits (12.5%), with 65% of participants having prior experience with telemedicine. The average age of study participants was 55 years old (SD 18 yrs;24-84 yrs). The majority of patients were white (69%), lived within the five boroughs of NYC (81%), and had higher levels of education (72% with a bachelor's or professional degree). There was a trend showing Manhattan residents having the greatest number of visits (39%) and higher overall satisfaction scores (98%) compared to other boroughs (P < 0.05). Patients aged 60-79 had lower satisfaction scores compared with other age groups (87% vs 97% for 20-39 yrs, 98% for 40-59 yrs, and 100% for 80+ yrs;P < 0.05). There were no differences in overall satisfaction among racial groups (P = 0.599), though those with advanced educational degrees trended towards higher satisfaction (P < 0.05). The most common reason for visits was for UTIs (31%), with overall satisfaction higher for visits regarding urinary complaints compared to those for prolapse or vulvovaginal complaints (P < 0.05). Altogether, high satisfaction rates were noted among the study population for scheduling (99%), technology (90%), provider interaction (96%), fulfillment of personal needs (91%), and overall satisfaction (94%). Conclusions: We demonstrate high patient satisfaction for telemedicine visits in a tertiary urogynecology clinic during the COVID-19 pandemic for a variety of indications, with greater satisfaction observed for those visits which may not necessitate an in-person exam (e.g., UTI). Patients with a high education level and close proximity to the medical center trended towards higher utilization and satisfaction.

LB-003 Ischemic stroke associated with covid-19 and racial outcome disparity in North America

IntroductionThere has been limited evidence on the influence of racial background in stroke outcomes in COVID-19. Underlying biological, genetic, or epigenetic characteristics may predispose to health differences and outcomes. Social determinants of health, access and geographical differences pertaining both to population density and other location-based factors may also be important.MethodsWe report 69 cases of acute stroke in patients positive for SARS-CoV-2, including 27 of African American background and 42 of other racial backgrounds, including Caucasian, Hispanic, and Asian. All patients presented to 14 major hospitals in the United States and Canada, from March 14-April 14, 2020. All patients had nasopharyngeal swab samples that were positive for SARS-CoV-2 on qualitative RT-PCR assays. We present a dichotomized analysis of ischemic stroke outcomes between patients of African American background as reported on hospital intake questionnaire versus all other backgrounds.ResultsComparison between Caucasian, Hispanic and Asian backgrounds did not show disparities in stroke outcomes. We found no significant difference in age (64.4 versus 62.9 years) or the proportion of females (51.9% versus 38.1%) (table 1). Diabetes mellitus was present significantly less in African American cases versus others (37% vs. 66.7%). No significant difference between groups was found regarding other comorbidities including smoking, atrial fibrillation, prior anticoagulation, coronary artery disease, congestive heart failure, hypertension, hyperlipidemia, cerebrovascular accident, peripheral vascular disease, or chronic kidney disease. With respect to presenting SARS-CoV-2 symptoms, we found no difference in exposure history, asymptomatic cases, fever, cough, dyspnea, nausea or vomiting, chills, malaise, or lethargy. The African American cohort had a similar mean NIHSS score of 16.3 compared with 14.9 in other races (p=0.63). The door-to-CT time was also similar (23 versus 19 minutes). The proportion of patients presenting with a large vessel occlusion was not significantly different (40.7% versus 47%). We noted 14.8% of African American cases received intravenous tPA compared to 31% in other races, but this was not significantly different in this sample. The proportion of thrombectomy cases mirrored this (14.8% versus 31%). Laboratory findings were not significantly different between African Americans and all others. Regarding stroke functional outcomes, there was no difference between African Americans and other races in terms of discharge mRS (p=0.27). For mRS 0–2, there was no significant difference noted (14.8% versus 16.7%). Symptomatic intracranial hemorrhage (sICH) was significantly higher for African Americans (11.1% versus 3%, p0.001). Mortality was significantly higher in African Americans compared to other races (51.9% vs. 28.6%, p=0.03).DiscussionOur preliminary data suggest that there may be a mortality difference amongst stroke patients of African American background afflicted with COVID-19. The reasons for increased mortality in African Americans with COVID-19-associated stroke are unknown. Racial disparities in case counts and outcomes during the COVID-19 pandemic have been highlighted, particularly regarding African American communities. In addition, the finding in this study that mortality rate of COVID-19 positive stroke patients is greater than that previously reported in either COVID-19 respiratory infection alone or acute ischemic stroke alone, suggests an interaction that also warrants further study.DisclosuresA. Dmytriw: None. K. Phan: None. C. Schirmer: None. F. Settecase: None. M. Heran: None. A. Efendizade: None. A. Kuhn: None. A. Puri: None. B. Menon: None. M. Dibas: None. S. Sivakumar: None. A. Mowla: None. L. Leung: None. A. Malek: None. B. Voetsch: None. S. Segal: None. A. Wakhloo: None. H. Wu: None. A. Xavier: None. A. Tiwari: None.