Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep). LIMITATION: The trial was prematurely stopped because of futility, limiting power for the primary outcome. CONCLUSION: Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. PRIMARY FUNDING SOURCE: National Institutes of Health.

Multidimensional aspects of dyspnea in obese patients referred for cardiopulmonary exercise testing.

We investigated the contributions of obesity on multidimensional aspects of dyspnea on exertion (DOE) in patients referred for clinical cardiopulmonary exercise testing (CPET). Ratings of perceived breathlessness (RPB, Borg scale 0-10) were collected in obese (BMI ≥ 30; n = 47) and nonobese (BMI ≤ 25; n = 27) patients during two (one lower: ∼30 W; and one higher: ∼50 W) 4-6 min constant load cycling bouts. Multidimensional dyspnea profiles (MDP) were collected in the final 26 obese and 14 nonobese patients of the sample. RPB was greater (p = 0.05) in obese (3.3 ± 2.2 vs 2.4 ± 1.4) at lower work rates, but similar at higher work rates (4.9 ± 2.2 vs 4.4 ± 1.8). MDP sensory score including unpleasantness was 4.3 ± 2.2 in obese vs 2.5 ± 1.9 in nonobese (p < 0.001). The affective score was 1.9 ± 2.2 vs 0.7 ± 0.7, respectively (p < 0.01). Breathing sensations including 'air hunger', 'effort', and 'breathing at lot' were greater (p < 0.05) in obese, making these patients more frustrated/angry (p < 0.05). Obesity should be considered as a potential independent influencing factor that provokes DOE and unpleasantness when assessing breathlessness during CPET.

Weight loss reduces dyspnea on exertion and unpleasantness of dyspnea in obese men.

We hypothesized that weight loss would ameliorate dyspnea on exertion (DOE) and feelings of unpleasantness related to the DOE in obese men. Eighteen men (34 ± 7yr, 35 ± 4 kg/m2 BMI, mean ± SD) participated in a 12-week weight loss program. Body composition, pulmonary function, cardiorespiratory measures, DOE, and unpleasantness (visual analog scale) were assessed before and after weight loss. Subjects were grouped by Ratings of Perceived Breathlessness (RPB, Borg 0-10 scale) during submaximal cycling: Ten men rated RPB ≥ 4 (+DOE), eight rated RPB ≤ 2 (-DOE). Subjects lost 10.3 ± 5.6 kg (9.2 ± 4.5%) of body weight (n = 18). RPB during submaximal cycling was significantly improved in both groups (+DOE: 4.1 ± 0.3-2.8 ± 1.1; -DOE: 1.3 ± 0.7 to 0.8 ± 0.6, p < 0.001). Several submaximal exercise variables (e.g., V˙O2, V˙E) were decreased similarly in both groups (p < 0.01). Unpleasantness associated with the DOE was reduced (p < 0.05). The improved RPB was not significantly correlated with changes in body weight or cardiopulmonary exercise responses (p > 0.05). Moderate weight loss appears to be an effective option to ameliorate DOE and unpleasantness related to DOE in obese men.

Dyspnea on exertion provokes unpleasantness and negative emotions in women with obesity.

PURPOSE: While dyspnea on exertion (DOE) is a common complaint in otherwise healthy obese women, less is known about feelings of unpleasantness and/or negative emotions provoked by DOE. We examined whether ratings of perceived breathlessness (RPB) during exercise were associated with ratings of unpleasantness and negative emotions (depression, anxiety, frustration, anger, and fear) in obese women. METHODS: Seventy-four women (34 ± 7 yrs, 36 ± 4 kg/m2, 46 ± 5% body fat) performed 6 min of constant-load cycling (60 W); RPB (0-10 scale), and unpleasantness and negative emotions (visual analog scales, 10 cm) were assessed at the end. RESULTS: RPB were significantly correlated with unpleasantness and negative emotions (p < 0.05). The strongest correlations were between RPB and unpleasantness (r = 0.61, p < 0.001), and RPB and anxiety (r = 0.50, p < 0.001). CONCLUSIONS: DOE can significantly provoke unpleasantness and negative emotions during exercise in obese women. This may affect their willingness to engage in regular physical activity.