ABSTRACT
Background: Passive immunization has a long history for infection prevention following exposure. We report results of a descriptive interim analysis from a study of an antibody “cocktail” of casirivimab with imdevimab (cas/imdev;formerly REGN-COV2) designed to bind non-competing epitopes of the viral spike protein, as a potential passive vaccine for the prevention of COVID-19 in people at risk of infection from household contact. Methods: In this ongoing Phase 3 study, asymptomatic participants exposed to a COVID-19-infected household member were randomized 1:1 to placebo or 1200 mg cas/imdev (600 mg of each antibody administered subcutaneously) within 96 hours of their household member testing positive. The analysis included participants who tested negative for SARS-CoV-2 by nasal, saliva, or nasopharyngeal swab and who were seronegative to SARS-CoV-2 antibodies at baseline. The proportion of participants who developed an RT-PCR-confirmed SARS-CoV-2 infection (asymptomatic or symptomatic) during the 1-month efficacy assessment period was summarized. Results: Initial results from the first evaluable 223 placebo and 186 cas/imdev participants who completed ≥29 days of the study are reported. Reduction in PCR-positive symptomatic disease was 100% (0/186 cas/imdev vs 8/223 placebo;OR 0.00 [CI 0.00, 0.69]). Reduction in any PCR-positive infection (symptomatic or asymptomatic) was 48% (10/186 vs 23/223;OR 0.49 [CI 0.20, 1.12]). Placebo-group participants had on average 100-fold higher peak viral load. In the cas/imdev group, viral RNA was not detected for longer than 1 week but was detected for 3-4 weeks in approximately 40% of placebo participants (Fig. 1). The proportions of infected participants with high viral loads (>10 4 copies/mL) were 13/21 placebo vs 0/9 cas/imdev. Total weeks of viral RNA detection and high viral load were 44 and 22 weeks in the placebo group vs 9 and 0 in the cas/imdev group. Total symptomatic weeks were 21 for placebo vs 0 for cas/imdev. A similar proportion of participants experienced at least 1 serious adverse event: placebo, 3/222 and cas/imdev, 1/186;none were deemed related to study treatment. Injection site reactions were similar: placebo, 1.4%;cas/ imdev, 2.6%. Conclusion: In this descriptive interim analysis of participants at risk of SARSCoV- 2 infection from household transmission, a subcutaneous dose of the cas/ imdev antibody cocktail prevented symptomatic infection, reduced overall infection, and decreased viral load and duration of viral RNA detection.
ABSTRACT
Background: Individuals hospitalized with COVID-19 exhibit a wide spectrum of disease. There is growing evidence that racial and ethnic minorities bear a disproportionate burden from COVID-19. Temporal changes in the pandemic epidemiology require careful study to identify determinants of poor outcomes. We assessed patient socio-demographics, comorbidities, baseline severity, treating hospital and pandemic month as independent risk factors for mortality and time to discharge. Methods: We analyzed 2500 individuals hospitalized with PCR-confirmed COVID-19 in 5 hospitals in the University of Pennsylvania Health System between March and September 2020, using electronic health records to assess outcomes through 8 weeks post-admission. Hospital discharge and mortality were analyzed as competing risks using a multivariable cause-specific hazards model. Results: Patients were 50.9% Black, 39.4% White and 9.7% other race;11% were Hispanic. Mortality decreased markedly over time, with cumulative incidence (95% CI) 30 days post-admission of 19.1% (17.2, 21.3) in March- April versus 6.3% (4.3, 8.9) in July-September;19% of deaths occurred after discharge. During this time, average age (SD) at admission declined from 62.7 (17.6) to 53.4 (20.6), ICU level care at admission increased from 16.5% to 18.6%, mechanical ventilation declined from 9.4% to 2.9%. Compared to Caucasian, Black race was associated with more severe disease at admission, a higher rate of co-morbidities and residence in low income zip code. In multivariable models, there were no detectable differences in mortality risk by race;while admitting hospital, increasing age, admission early in the pandemic, and severe disease and low blood pressure at admission were associated with increased mortality hazard (Figure 1). Mortality appeared similar between sexes, though males tended to have longer hospital stays (discharge hazard ratio 0.82 (95% CI: 0.75, 0.90)). Hispanic ethnicity was associated with fewer baseline co-morbidities and lower mortality hazard (0.57, 95% CI: 0.37, .087). Conclusion: We found that morbidity and mortality for hospitalized COVID-19 patients substantially decreased over time but post-discharge mortality remained non-trivial. Black race was associated with more risk factors for morbidity and with treatment at hospitals with lower mortality. In multivariable models, there were no detectable race differences in hospital outcomes. Future work is needed to better understand the identified betweenhospital differences in mortality.