ABSTRACT
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.
ABSTRACT
Study Objectives: Rapid response teams (RRT) aim to reduce morbidity and mortality of hospitalized patients through early intervention on those who are clinically deteriorating. Identifying predictors of early deterioration of patients may improve quality and safety. Abnormal vital signs (VS) have previously been studied as predictors of early deterioration and increased RRT activation after admission from the ED. The primary objective is to identify these predictors of RRT activation within 24 hours of admission. Secondary objectives are to detect differences in hospital length-of-stay (LOS), admitting diagnoses, and 30-day mortality in those with and without RRT (+RRT and –RRT). Last, we examine the predictive value of physician clinical gestalt on RRTs. Methods: This was a prospective, observational case-control study by chart review of adult patients admitted at Kaweah Health Medical Center between December 2020 and March 2021. Exclusion criteria were age <18, admission to ICU, and direct transfer out of the ED. At time of admission, we performed chart review to collect eight VS used to activate a RRT at our hospital. To determine clinician gestalt, the physician was also asked if RRT would occur within 24 hours. Each patient’s hospital course was later reviewed for the occurrence of RRT, admitting diagnoses, LOS, and 30-day mortality. Categorical variables were analyzed using Fisher’s exact test. Noncategorical variables were analyzed using Wilcoxon rank sum test, independent T-test, and Pearson correlation coefficient. Predictive value was analyzed with negative and positive predictive values (NPV and PPV), sensitivity, and specificity. Results: 199 patients met inclusion/exclusion criteria for analysis (+RRT N=3, -RRT N=196). No significant differences were detected in sex, age, or level of care between our groups. The groups differed in median heart rate and respiratory rate, but the difference was insignificant. There was a marginally significant association between COVID-19 as admitting diagnosis and RRT (p=0.052). There was no significant association between RRT and 30-day mortality. Mean LOS did not differ between the groups (p=0.297). The mean number of abnormal VS in those deceased at 30 days (1.2) was significantly higher than those alive at 30 days (0.7) (p=0.047, correlation coefficient r=0.14). Analysis of clinical gestalt on RRT showed PPV 3.2%, NPV 98.8%, sensitivity 33.3%, and specificity 84.5%. Conclusion: Due to small sample size, our results did not show significant differences in sex, age, level of care, heart rate, respiratory rate, or LOS between the +RRT and –RRT groups. However, our study was significant for three findings. First, there was a marginally significant association between an admitting diagnosis of COVID-19 and RRT. Second, patients deceased within 30 days had a significantly higher number of abnormal VS than patients who were alive at 30 days, suggesting a positive correlation. Third, results suggest that the clinical gestalt of emergency physicians at predicting who will not have an RRT is reasonably good, but may not be as good at predicting who will have an RRT. Further studies determining other factors contributing to early deterioration can help craft interventions to improve patient safety. [Formula presented]
ABSTRACT
BACKGROUND: The COVID-19 New Mum Study is recording maternal experiences and infant feeding during the UK lockdown. This report from week 1 of the survey describes and compares the delivery and post-natal experiences of women who delivered before (BL) versus during (DL) the lockdown. METHODS: Women living in the UK aged ≥18 years with an infant ≤12 months of age completed an anonymous online survey (https://is.gd/covid19newmumstudy). Information/links are shared via websites, social media and existing contacts. RESULTS: From 27.5.20-3.6.20, 1365 women provided data (94% white, 95% married/with partner, 66% degree/higher qualification, 86% living in house; 1049 (77%) delivered BL and 316 (23%) DL. Delivery mode, skin-to-skin contact and breastfeeding initiation did not differ between groups. DL women had shorter hospital stays (p < 0.001). 39% reported changes to their birth plan. Reflecting younger infant age, 59% of DL infants were exclusively breast-fed/mixed fed versus 39% of BL (p < 0.05). 13% reported a change in feeding; often related to lack of breastfeeding support, especially with practical problems. Important sources of feeding support were the partner (60%), health professional (50%) and online groups (47%). 45% of DL women reported insufficient feeding support. Among BL women, 57% and 69% reported decreased feeding support and childcare, respectively. 40% BL/45% DL women reported insufficient support with their own health, 8%/9% contacted a mental health professional; 11% reported their mental health was affected. 9% highlighted lack of contact/support from family and distress that they had missed seeing the baby. CONCLUSION: Lockdown has impacted maternal experiences, resulting in distress for many women. Our findings suggest the need for better infant feeding support, especially 'face-to-face' support for practical issues; and recognising and supporting mothers who are struggling with mental health challenges or other aspects of their health. The effectiveness of online versus face-to-face contact is currently uncertain, and requires further evaluation.