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.).

Comparative healing of human cutaneous surgical incisions created by the PEAK PlasmaBlade, conventional electrosurgery, and a standard scalpel.

BACKGROUND: The authors investigated thermal injury depth, inflammation, and scarring in human abdominal skin by comparing the histology of incisions made with a standard "cold" scalpel blade, conventional electrosurgery, and the PEAK PlasmaBlade, a novel, low-thermal-injury electrosurgical instrument. METHODS: Approximately 6 and 3 weeks before abdominoplasty, full-thickness incisions were created in the abdominal pannus skin of 20 women, using a scalpel (scalpel), the PlasmaBlade, and a conventional electrosurgical instrument. Fresh (0-week) incisions were made immediately before surgery. After abdominoplasty, harvested incisions were analyzed for scar width, thermal injury depth, burst strength, and inflammatory response. RESULTS: Acute thermal injury depth was reduced 74 percent in PlasmaBlade incisions compared with conventional electrosurgical instrument (p < 0.001). Significant differences in inflammatory response were observed at 3 weeks, with mean CD3 response (T-lymphocytes) 40 percent (p = 0.01) and 21 percent (p ≈ 0.12) higher for the conventional electrosurgical instrument and PlasmaBlade, respectively, compared with the scalpel. CD68 response (monocytes/macrophages) was 52 percent (p = 0.05) and 16 percent (p ≈ 0.35) greater for a conventional electrosurgical instrument and the PlasmaBlade, respectively. PlasmaBlade incisions demonstrated 65 percent (p < 0.001) and 42 percent (p < 0.001) stronger burst strength than a conventional electrosurgical instrument, with equivalence to the scalpel at the 3- and 6-week time points, respectively. Scar width was equivalent for the PlasmaBlade and the scalpel at both time points, and 25 percent (p = 0.01) and 12 percent (p = 0.15) less than for electrosurgery, respectively. CONCLUSIONS: PlasmaBlade incisions demonstrated reduced thermal injury depth, inflammatory response, and scar width in healing skin compared with electrosurgery. These results suggest that the PlasmaBlade may provide clinically meaningful advantages over conventional electrosurgery during human cutaneous wound healing. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.(Figure is included in full-text article.).